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Sample records for nanoparticle hyperthermia cancer

  1. Iron oxide nanoparticle hyperthermia and chemotherapy cancer treatment

    Petryk, A. A.; Giustini, A. J.; Ryan, P.; Strawbridge, R. R.; Hoopes, P. J.

    2009-02-01

    The benefit of combining hyperthermia and chemotherapy to treat cancer is well established. However, combined therapy has not yet achieved standard of care status. The reasons are numerous and varied, however the lack of significantly greater tumor cell sensitivity to heat (as compared to normal cells) and the inability to deliver heat to the tumor in a precise manner have been major factors. Iron oxide nanoparticle (IONP) hyperthermia, alone and combined with other modalities, offers a new direction in hyperthermia cancer therapy via improved tumor targeting and an improved therapeutic ratio. Our preliminary studies have demonstrated tumor cell cytotoxicity (in vitro and in vivo) with IONP heat and cisplatinum (CDDP) doses lower than those necessary when using conventional heating techniques or cisplatinum alone. Ongoing studies suggest such treatment could be further improved through the use of targeted nanoparticles.

  2. Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

    Petryk, Alicia Ailie

    Magnetic nanoparticle hyperthermia (mNPH) is an emerging cancer therapy which has shown to be most effective when applied in the adjuvant setting with chemotherapy, radiation or surgery. Although mNPH employs heat as a primary therapeutic modality, conventional heat may not be the only cytotoxic effect. As such, my studies have focused on the mechanism and use of mNPH alone and in conjunction with cisplatinum chemotherapy in murine breast cancer cells and a related in vivo model. MNPH was compared to conventional microwave tumor heating, with results suggesting that mNPH (mNP directly injected into the tumor and immediately activated) and 915 MHz microwave hyperthermia, at the same thermal dose, result in similar tumor regrowth delay kinetics. However, mNPH shows significantly less peri-tumor normal tissue damage. MNPH combined with cisplatinum also demonstrated significant improvements in regrowth delay over either modality applied as a monotherapy. Additional studies demonstrated that a relatively short tumor incubation time prior to AMF exposure (less than 10 minutes) as compared to a 4-hour incubation time, resulted in faster heating rates, but similar regrowth delays when treated to the same thermal dose. The reduction of heating rate correlated well with the observed reduction in mNP concentration in the tumor observed with 4 hour incubation. The ability to effectively deliver cytotoxic mNPs to metastatic tumors is the hope and goal of systemic mNP therapy. However, delivering relevant levels of mNP is proving to be a formidable challenge. To address this issue, I assessed the ability of cisplatinum to simultaneously treat a tumor and improve the uptake of systemically delivered mNPs. Following a cisplatinum pretreatment, systemic mNPs uptake was increased by 3.1 X, in implanted murine breast tumors. Additional in vitro studies showed the necessity of a specific mNP/ Fe architecture and spatial relation for heat-based cytotoxicity in cultured cells.

  3. Similarities and differences in ablative and non-ablative iron oxide nanoparticle hyperthermia cancer treatment

    Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Mazur, Courtney M.; Petryk, James D.; Hoopes, P. Jack

    2015-03-01

    The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. It has been demonstrated by many research groups that ablative temperatures and cytotoxicity can be produced with locally NP-based hyperthermia. Such ablative NP techniques have demonstrated the potential for success. Much attention has also been given to the fact that NP may be administered systemically, resulting in a broader cancer therapy approach, a lower level of tumor NP content and a different type of NP cancer therapy (most likely in the adjuvant setting). To use NP based hyperthermia successfully as a cancer treatment, the technique and its goal must be understood and utilized in the appropriate clinical context. The parameters include, but are not limited to, NP access to the tumor (large vs. small quantity), cancer cell-specific targeting, drug carrying capacity, potential as an ionizing radiation sensitizer, and the material properties (magnetic characteristics, size and charge). In addition to their potential for cytotoxicity, the material properties of the NP must also be optimized for imaging, detection and direction. In this paper we will discuss the differences between, and potential applications for, ablative and non-ablative magnetic nanoparticle hyperthermia.

  4. Clinical hyperthermia of prostate cancer using magnetic nanoparticles - preliminary experience with a new interstitial technique

    Johannsen, M.; Gneveckow, U.; Eckelt, L.; Feussner, A.; Waldoefner, N.; Scholz, R.; Deger, S.; Wust, P.; Loening, S.A.; Jordan, A.

    2005-01-01

    Full text: Thermotherapy using biocompatible superparamagnetic nanoparticles, also referred to as magnetic fluid hyperthermia (MFH), has been shown to inhibit prostate cancer growth in the Dunning rat model. Here we present the first clinical application of interstitial hyperthermia using magnetic nanoparticles in locally recurrent prostate cancer. Treatment planning was carried out using computerized tomography (CT) of the prostate. Based on the individual anatomy of the prostate and the estimated specific absorption rate (SAR) of magnetic fluids in prostatic tissue, the number and position of magnetic fluid depots required for sufficient heat deposition was calculated using the AMIRA software and a newly developed prostate module. Nanoparticle suspensions (MagForce MFL AS, MagForce Nanotechnologies GmbH, Berlin, Germany) were injected transperineally into the prostate under transrectal ultrasound and flouroscopy guidance. Treatments were delivered in the first magnetic field applicator for use in humans (MFH300F, MagForce Nanotechnologies GmbH, Berlin), using an alternating magnetic field with a frequency of 100 kHz and variable field strength (0-18 kA/m). Invasive thermometry of the prostate was carried out in the first and last of 6 weekly hyperthermia sessions of 60 min duration. CT-scans of the prostate were repeated following the first and last hyperthermia treatment to document magnetic nanoparticle distribution and the position of the thermometry probes in the prostate. Nanoparticles were retained in the prostate during the treatment interval of 6 weeks, as documented by CT. Treatment was well tolerated. During the first treatment, maximum intra-prostatic temperatures measured by 4 thermometry probes at a magnetic field strength of 4.0-5.0 kA/m were 48.5, 43.0, 43.7 and 43.6 o C, whereas minimal temperatures were 41.2, 40.3, 40.0 and 41.1 o C, respectively. During the sixth and last treatment of the same patient, maximum intraprostatic temperatures were 42

  5. A newly developed Fe-doped calcium sulfide nanoparticles with magnetic property for cancer hyperthermia

    Wu, Steven Yueh-Hsiu; Tseng, Ching-Li; Lin, Feng-Huei

    2010-05-01

    In this study, a magnetic iron-doped calcium sulfide (Fe-CaS) nanoparticle was newly developed and studied for the purpose of hyperthermia due to its promising magnetic property, adequate biodegradation rate, and relatively good biocompatibility. Fe-CaS nanoparticles were synthesized by a wet chemical co-precipitation process with heat treatment in a N2 atmosphere, and were subsequently cooled in N2 and exposed to air at a low temperature. The crystal structure of the Fe-CaS nanoparticles was similar to that of the CaS, which was identified by an X-ray diffractometer (XRD). The particle size was less than 40 nm based on a Debye-Scherrer equation and transmission electron microscope (TEM) examination. Magnetic properties obtained from the SQUID magnetometer demonstrated that the synthesized CaS was a diamagnetic property. Once the Fe ions were doped, the synthesized Fe-CaS converted into paramagnetism which showed no hysteresis loop. Having been heated above 600 °C in N2, the Fe-CaS showed a promising magnetic property to produce enough energy to increase the temperature for hyperthermia. 10 mg/ml of the Fe-CaS was able to generate heat to elevate the media temperature over 42.5 °C within 6 min. The area of the hysteresis loop increased with the increasing of the treated temperature, especially at 800 °C for 1 h. This is because more Fe ions replaced Ca ions in the lattice at the higher heat treatment temperature. The heat production was also increasing with the increasing of heat treatment temperature, which resulted in an adequate specific absorption ratio (SAR) value, which was found to be 45.47 W/g at 37 °C under an alternative magnetic field of f = 750 KHz , H = 10 Oe. The in vitro biocompatibility test of the synthesized Fe-CaS nanoparticles examined by the LDH assay showed no cytotoxicity to 3T3 fibroblast. The result of in vitro cell hyperthermia shows that under magnetic field the Fe-CaS nanoparticles were able to generate heat and kill the CT-26 cancer

  6. A newly developed Fe-doped calcium sulfide nanoparticles with magnetic property for cancer hyperthermia

    Wu, Steven Yueh-Hsiu; Tseng, Ching-Li; Lin, Feng-Huei

    2010-01-01

    cancer cells significantly. We believe that the developed Fe-CaS nanoparticles have great potential as thermo-seeds for cancer hyperthermia in the near future.

  7. In vitro application of Fe/MgO nanoparticles as magnetically mediated hyperthermia agents for cancer treatment

    Chalkidou, A. [Department of Physics, Aristotle University of Thessaloniki, 54 124 Thessaloniki (Greece); Molecular Oncology Laboratory, Theagenio Cancer Hospital, Alexandrou Simeonidi Street 2, 54 007 Thessaloniki (Greece); Simeonidis, K. [Department of Physics, Aristotle University of Thessaloniki, 54 124 Thessaloniki (Greece); Angelakeris, M., E-mail: agelaker@auth.g [Department of Physics, Aristotle University of Thessaloniki, 54 124 Thessaloniki (Greece); Samaras, T. [Department of Physics, Aristotle University of Thessaloniki, 54 124 Thessaloniki (Greece); Martinez-Boubeta, C. [Departament d' Electronica, Universitat de Barcelona, Marti i Franques 1, Barcelona 08028 (Spain); Balcells, Ll. [ICMAB-CSIC, Campus UAB, Bellaterra 08193 (Spain); Papazisis, K. [Molecular Oncology Laboratory, Theagenio Cancer Hospital, Alexandrou Simeonidi Street 2, 54 007 Thessaloniki (Greece); Dendrinou-Samara, C. [Department of Chemistry, Aristotle University of Thessaloniki, 54 124 Thessaloniki (Greece); Kalogirou, O. [Department of Physics, Aristotle University of Thessaloniki, 54 124 Thessaloniki (Greece)

    2011-03-15

    In this work we study the heating efficiency of Fe/MgO magnetic core/biocompatible shell nanoparticles and their in vitro application in magnetic hyperthermia on cancer cells. Different human breast cancer cell lines were used to assess the suitability of nanoparticles for in vivo application. The experiments revealed a very good cytotoxicity profile and significant uptake efficiency together with relatively high specific absorption rates and fast thermal response, features that are crucial for adequate thermal efficiency and minimum duration of treatment. - Research highlights: > Fe/MgO magnetic core/shell nanoparticles and their in vitro application for magnetic hyperthermia. > Very good cytotoxicity profile and significant uptake efficiency in three human breast cancer cell lines. > SAR values and fast thermal response guarantee adequate thermal efficiency and minimum treatment duration.

  8. Silica-modified Fe-doped calcium sulfide nanoparticles for in vitro and in vivo cancer hyperthermia

    Wu, Steven Yueh-Hsiu; Yang, Kai-Chiang; Tseng, Ching-Li; Chen, Jung-Chih; Lin, Feng-Huei

    2011-01-01

    In this study, sulfide-based magnetic Fe-doped CaS nanoparticles modified with a silica layer were investigated for cancer hyperthermia. A polyvinyl pyrrolidone polymer was used as the coupling agent. The developed nanoparticles contained 11.6 wt% iron concentration, and their X-ray diffraction pattern was similar to those of CaS and Fe–CaS nanoparticles. The average particle size was approximately 47.5 nm and homogeneously dispersed in aqueous solutions. The major absorption bands of silica were observed from the FTIR spectrum. The magnetic properties and heating efficiency were also examined. The specific absorption ratio of nanoparticles at a concentration of 10 mg/mL at 37 °C in an ethanol carrier fluid was 37.92 W/g, and the nanoparticles would raise the temperature to over 45 °C within 15 min. A cytotoxicity analysis revealed that the nanoparticles had good biocompatibility, which indicated that the nanoparticles did not affect cell viability. The therapeutic effects of the nanoparticles were investigated using in vitro and animal studies. Cells seeded with nanoparticles and treated under an AC magnetic field revealed a percentage of cytotoxicity (60%) that was significantly higher from that in other groups. In the animal study, during a hyperthermia period of 15 days, tumor-bearing Balb/c mice that were subcutaneously injected with nanoparticles and exposed to an AC magnetic field manifested a reduction in tumor volume. The newly developed silica-modified Fe–CaS nanoparticles can thus be considered a promising and attractive hyperthermia thermoseed.

  9. Heating efficiency in magnetic nanoparticle hyperthermia

    Deatsch, Alison E.; Evans, Benjamin A.

    2014-01-01

    Magnetic nanoparticles for hyperthermic treatment of cancers have gained significant attention in recent years. In magnetic hyperthermia, three independent mechanisms result in thermal energy upon stimulation: Néel relaxation, Brownian relaxation, and hysteresis loss. The relative contribution of each is strongly dependent on size, shape, crystalline anisotropy, and degree of aggregation or agglomeration of the nanoparticles. We review the effects of each of these physical mechanisms in light of recent experimental studies and suggest routes for progress in the field. Particular attention is given to the influence of the collective behaviors of nanoparticles in suspension. A number of recent studies have probed the effect of nanoparticle concentration on heating efficiency and have reported superficially contradictory results. We contextualize these studies and show that they consistently indicate a decrease in magnetic relaxation time with increasing nanoparticle concentration, in both Brownian- and Néel-dominated regimes. This leads to a predictable effect on heating efficiency and alleviates a significant source of confusion within the field. - Highlights: • Magnetic nanoparticle hyperthermia. • Heating depends on individual properties and collective properties. • We review recent studies with respect to loss mechanisms. • Collective behavior is a key source of confusion in the field. • We contextualize recent studies to elucidate consistencies and alleviate confusion

  10. Investigation properties of superparamagnetic nanoparticles and magnetic field-dependent hyperthermia therapy

    Hedayatnasab, Z.; Abnisa, F.; Daud, W. M. A. Wan

    2018-03-01

    The application of superparamagnetic nanoparticles as heating agents in hyperthermia therapy has made a therapeutic breakthrough in cancer treatment. The high efficiency of this magnetic hyperthermia therapy has derived from a great capability of superparamagnetic nanoparticles to generate focused heat in inaccessible tumors being effectively inactivated. The main challenges of this therapy are the improvement of the induction heating power of superparamagnetic nanoparticles and the control of the hyperthermia temperature in a secure range of 42 °C to 47 °C, at targeted area. The variation of these hyperthermia properties is principally dependent on the magnetic nanoparticles as well as the magnetic field leading to enhance the efficiency of magnetic hyperthermia therapy at targeted area and also avoid undue heating to healthy cells. The present study evaluates the magnetic hyperthermia therapy through the determination of superparamagnetic nanoparticles properties and magnetic field’ parameters.

  11. The Dartmouth Center for Cancer Nanotechnology Excellence: magnetic hyperthermia.

    Baker, Ian; Fiering, Steve N; Griswold, Karl E; Hoopes, P Jack; Kekalo, Katerina; Ndong, Christian; Paulsen, Keith; Petryk, Alicea A; Pogue, Brian; Shubitidze, Fridon; Weaver, John

    2015-01-01

    The Dartmouth Center for Cancer Nanotechnology Excellence - one of nine funded by the National Cancer Institute as part of the Alliance for Nanotechnology in Cancer - focuses on the use of magnetic nanoparticles for cancer diagnostics and hyperthermia therapy. It brings together a diverse team of engineers and biomedical researchers with expertise in nanomaterials, molecular targeting, advanced biomedical imaging and translational in vivo studies. The goal of successfully treating cancer is being approached by developing nanoparticles, conjugating them with Fabs, hyperthermia treatment, immunotherapy and sensing treatment response.

  12. A smart platform for hyperthermia application in cancer treatment: cobalt-doped ferrite nanoparticles mineralized in human ferritin cages.

    Fantechi, Elvira; Innocenti, Claudia; Zanardelli, Matteo; Fittipaldi, Maria; Falvo, Elisabetta; Carbo, Miriam; Shullani, Valbona; Di Cesare Mannelli, Lorenzo; Ghelardini, Carla; Ferretti, Anna Maria; Ponti, Alessandro; Sangregorio, Claudio; Ceci, Pierpaolo

    2014-05-27

    Magnetic nanoparticles, MNPs, mineralized within a human ferritin protein cage, HFt, can represent an appealing platform to realize smart therapeutic agents for cancer treatment by drug delivery and magnetic fluid hyperthermia, MFH. However, the constraint imposed by the inner diameter of the protein shell (ca. 8 nm) prevents its use as heat mediator in MFH when the MNPs comprise pure iron oxide. In this contribution, we demonstrate how this limitation can be overcome through the controlled doping of the core with small amount of Co(II). Highly monodisperse doped iron oxide NPs with average size of 7 nm are mineralized inside a genetically modified variant of HFt, carrying several copies of α-melanocyte-stimulating hormone peptide, which has already been demonstrated to have excellent targeting properties toward melanoma cells. HFt is also conjugated to poly(ethylene glycol) molecules to increase its in vivo stability. The investigation of hyperthermic properties of HFt-NPs shows that a Co doping of 5% is enough to strongly enhance the magnetic anisotropy and thus the hyperthermic efficiency with respect to the undoped sample. In vitro tests performed on B16 melanoma cell line demonstrate a strong reduction of the cell viability after treatment with Co doped HFt-NPs and exposure to the alternating magnetic field. Clear indications of an advanced stage of apoptotic process is also observed from immunocytochemistry analysis. The obtained data suggest this system represents a promising candidate for the development of a protein-based theranostic nanoplatform.

  13. Thermoseeds for interstitial magnetic hyperthermia: from bioceramics to nanoparticles

    Baeza, A; Arcos, D; Vallet-Regí, M

    2013-01-01

    The development of magnetic materials for interstitial hyperthermia treatment of cancer is an ever evolving research field which provides new alternatives to antitumoral therapies. The development of biocompatible magnetic materials has resulted in new biomaterials with multifunctional properties, which are able to adapt to the complex scenario of tumoral processes. Once implanted or injected in the body, magnetic materials can behave as thermoseeds under the effect of AC magnetic fields. Magnetic bioceramics aimed to treat bone tumors and magnetic nanoparticles are among the most studied thermoseeds, and supply different solutions for the different scenarios in cancerous processes. This paper reviews some of the biomaterials used for bone cancer treatment and skeletal reinforcing, as well as the more complex topic of magnetic nanoparticles for intracellular targeting and hyperthermia. (topical review)

  14. Computational evaluation of amplitude modulation for enhanced magnetic nanoparticle hyperthermia.

    Soetaert, Frederik; Dupré, Luc; Ivkov, Robert; Crevecoeur, Guillaume

    2015-10-01

    Magnetic nanoparticles (MNPs) can interact with alternating magnetic fields (AMFs) to deposit localized energy for hyperthermia treatment of cancer. Hyperthermia is useful in the context of multimodality treatments with radiation or chemotherapy to enhance disease control without increased toxicity. The unique attributes of heat deposition and transfer with MNPs have generated considerable attention and have been the focus of extensive investigations to elucidate mechanisms and optimize performance. Three-dimensional (3D) simulations are often conducted with the finite element method (FEM) using the Pennes' bioheat equation. In the current study, the Pennes' equation was modified to include a thermal damage-dependent perfusion profile to improve model predictions with respect to known physiological responses to tissue heating. A normal distribution of MNPs in a model liver tumor was combined with empirical nanoparticle heating data to calculate tumor temperature distributions and resulting survival fraction of cancer cells. In addition, calculated spatiotemporal temperature changes were compared among magnetic field amplitude modulations of a base 150-kHz sinusoidal waveform, specifically, no modulation, sinusoidal, rectangular, and triangular modulation. Complex relationships were observed between nanoparticle heating and cancer tissue damage when amplitude modulation and damage-related perfusion profiles were varied. These results are tantalizing and motivate further exploration of amplitude modulation as a means to enhance efficiency of and overcome technical challenges associated with magnetic nanoparticle hyperthermia (MNH).

  15. Utility and translatability of mathematical modeling, cell culture and small and large animal models in magnetic nanoparticle hyperthermia cancer treatment research

    Hoopes, P. J.; Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Pearce, John A.; Ryan, Thomas P.

    2015-03-01

    For more than 50 years, hyperthermia-based cancer researchers have utilized mathematical models, cell culture studies and animal models to better understand, develop and validate potential new treatments. It has been, and remains, unclear how and to what degree these research techniques depend on, complement and, ultimately, translate accurately to a successful clinical treatment. In the past, when mathematical models have not proven accurate in a clinical treatment situation, the initiating quantitative scientists (engineers, mathematicians and physicists) have tended to believe the biomedical parameters provided to them were inaccurately determined or reported. In a similar manner, experienced biomedical scientists often tend to question the value of mathematical models and cell culture results since those data typically lack the level of biologic and medical variability and complexity that are essential to accurately study and predict complex diseases and subsequent treatments. Such quantitative and biomedical interdependence, variability, diversity and promise have never been greater than they are within magnetic nanoparticle hyperthermia cancer treatment. The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and, recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. The goal of this paper is to use proven concepts and current research to address the potential pathobiology, modeling and quantification of the effects of treatment as pertaining to the similarities and differences in energy delivered by known external delivery techniques and iron oxide nanoparticles.

  16. Magnetic hyperthermia with hard-magnetic nanoparticles

    Kashevsky, Bronislav E., E-mail: bekas@itmo.by [A.V Luikov Heat and Mass Transfer Institute, Belarus Academy of Sciences, P. Brovka str. 15, Minsk 220072 (Belarus); Kashevsky, Sergey B.; Korenkov, Victor S. [A.V Luikov Heat and Mass Transfer Institute, Belarus Academy of Sciences, P. Brovka str. 15, Minsk 220072 (Belarus); Istomin, Yuri P. [N. N. Alexandrov National Cancer Center of Belarus, Lesnoy-2, Minsk 223040 (Belarus); Terpinskaya, Tatyana I.; Ulashchik, Vladimir S. [Institute of Physiology, Belarus Academy of Sciences, Akademicheskaya str. 28, Minsk 220072 (Belarus)

    2015-04-15

    Recent clinical trials of magnetic hyperthermia have proved, and even hardened, the Ankinson-Brezovich restriction as upon magnetic field conditions applicable to any site of human body. Subject to this restriction, which is harshly violated in numerous laboratory and small animal studies, magnetic hyperthermia can relay on rather moderate heat source, so that optimization of the whole hyperthermia system remains, after all, the basic problem predetermining its clinical perspectives. We present short account of our complex (theoretical, laboratory and small animal) studies to demonstrate that such perspectives should be related with the hyperthermia system based on hard-magnetic (Stoner–Wohlfarth type) nanoparticles and strong low-frequency fields rather than with superparamagnetic (Brownian or Neél) nanoparticles and weak high-frequency fields. This conclusion is backed by an analytical evaluation of the maximum absorption rates possible under the field restriction in the ideal hard-magnetic (Stoner–Wohlarth) and the ideal superparamagnetic (single relaxation time) systems, by theoretical and experimental studies of the dynamic magnetic hysteresis in suspensions of movable hard-magnetic particles, by producing nanoparticles with adjusted coercivity and suspensions of such particles capable of effective energy absorption and intratumoral penetration, and finally, by successful treatment of a mice model tumor under field conditions acceptable for whole human body. - Highlights: • Hard-magnetic nanoparticles are shown superior for hyperthetmia to superparamagnetic. • Optimal system parameters are found from magnetic reversal model in movable particle. • Penetrating suspension of HM particles with aggregation-independent SAR is developed. • For the first time, mice with tumors are healed in AC field acceptable for human body.

  17. Synthesis, characterization and in vitro study of biocompatible cinnamaldehyde functionalized magnetite nanoparticles (CPGF Nps for hyperthermia and drug delivery applications in breast cancer.

    Kirtee D Wani

    Full Text Available Cinnamaldehyde, the bioactive component of the spice cinnamon, and its derivatives have been shown to possess anti-cancer activity against various cancer cell lines. However, its hydrophobic nature invites attention for efficient drug delivery systems that would enhance the bioavailability of cinnamaldehyde without affecting its bioactivity. Here, we report the synthesis of stable aqueous suspension of cinnamaldehyde tagged Fe3O4 nanoparticles capped with glycine and pluronic polymer (CPGF NPs for their potential application in drug delivery and hyperthermia in breast cancer. The monodispersed superparamagnetic NPs had an average particulate size of ∼ 20 nm. TGA data revealed the drug payload of ∼ 18%. Compared to the free cinnamaldehyde, CPGF NPs reduced the viability of breast cancer cell lines, MCF7 and MDAMB231, at lower doses of cinnamaldehyde suggesting its increased bioavailability and in turn its therapeutic efficacy in the cells. Interestingly, the NPs were non-toxic to the non-cancerous HEK293 and MCF10A cell lines compared to the free cinnamaldehyde. The novelty of CPGF nanoparticulate system was that it could induce cytotoxicity in both ER/PR positive/Her2 negative (MCF7 and ER/PR negative/Her2 negative (MDAMB231 breast cancer cells, the latter being insensitive to most of the chemotherapeutic drugs. The NPs decreased the growth of the breast cancer cells in a dose-dependent manner and altered their migration through reduction in MMP-2 expression. CPGF NPs also decreased the expression of VEGF, an important oncomarker of tumor angiogenesis. They induced apoptosis in breast cancer cells through loss of mitochondrial membrane potential and activation of caspase-3. Interestingly, upon exposure to the radiofrequency waves, the NPs heated up to 41.6 °C within 1 min, suggesting their promise as a magnetic hyperthermia agent. All these findings indicate that CPGF NPs prove to be potential nano-chemotherapeutic agents in breast cancer.

  18. Nanotechnology in hyperthermia cancer therapy: From fundamental principles to advanced applications.

    Beik, Jaber; Abed, Ziaeddin; Ghoreishi, Fatemeh S; Hosseini-Nami, Samira; Mehrzadi, Saeed; Shakeri-Zadeh, Ali; Kamrava, S Kamran

    2016-08-10

    In this work, we present an in-depth review of recent breakthroughs in nanotechnology for hyperthermia cancer therapy. Conventional hyperthermia methods do not thermally discriminate between the target and the surrounding normal tissues, and this non-selective tissue heating can lead to serious side effects. Nanotechnology is expected to have great potential to revolutionize current hyperthermia methods. To find an appropriate place in cancer treatment, all nanotechnology-based hyperthermia methods and their risks/benefits must be thoroughly understood. In this review paper, we extensively examine and compare four modern nanotechnology-based hyperthermia methods. For each method, the possible physical mechanisms of heat generation and enhancement due to the presence of nanoparticles are explained, and recent in vitro and in vivo studies are reviewed and discussed. Nano-Photo-Thermal Therapy (NPTT) and Nano-Magnetic Hyperthermia (NMH) are reviewed as the two first exciting approaches for targeted hyperthermia. The third novel hyperthermia method, Nano-Radio-Frequency Ablation (NaRFA) is discussed together with the thermal effects of novel nanoparticles in the presence of radiofrequency waves. Finally, Nano-Ultrasound Hyperthermia (NUH) is described as the fourth modern method for cancer hyperthermia. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Ferromagnetic nanoparticles for magnetic hyperthermia and thermoablation therapy

    Kita, Eiji; Kayano, Takeru; Sato, Suguru; Minagawa, Makoto; Yanagihara, Hideto; Kishimoto, Mikio [Institute of Applied Physics, University of Tsukuba, Tsukuba 305-8573 (Japan); Oda, Tatsuya; Hashimoto, Shinji; Yamada, Keiichi; Ohkohchi, Nobuhiro [Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba 305-8575 (Japan); Mitsumata, Chiharu, E-mail: kita@bk.tsukuba.ac.j [Department of Electronic Engineering, Graduate School of Engineering, Tohoku University, Sendai 980-8579 (Japan)

    2010-12-01

    The use of ferromagnetic nanoparticles for hyperthermia and thermoablation therapies has shown great promise in the field of nanobiomedicine. Even local hyperthermia offers numerous advantages as a novel cancer therapy; however, it requires a remarkably high heating power of more than 1 kW g{sup -1} for heat agents. As a candidate for high heat generation, we focus on ferromagnetic nanoparticles and compare their physical properties with those of superparamagnetic substances. Numerical simulations for ideal single-domain ferromagnetic nanoparticles with cubic and uniaxial magnetic symmetries were carried out and MH curves together with minor loops were obtained. From the simulation, the efficient use of an alternating magnetic field (AMF) having a limited amplitude was discussed. Co-ferrite nanoparticles with various magnitudes of coercive force were produced by co-precipitation and a hydrothermal process. A maximum specific loss power of 420 W g{sup -1} was obtained using an AMF at 117 kHz with H{sub 0} = 51.4 kA m{sup -1} (640 Oe). The relaxation behaviour in the ferromagnetic state below the superparamagnetic blocking temperature was examined by Moessbauer spectroscopy.

  20. Therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia using Fe{sub 2}O{sub 3} nanoparticles

    Yan, S.Y.; Chen, M.M.; Fan, J.G.; Wang, Y.Q.; Hu, Y.; Xu, L.M., E-mail: leiming.xu@aliyun.com.cn, E-mail: huying@sohu.com [Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Du, Y.Q. [Department of Pathology, Cancer Hospital, Fudan University, Shanghai (China)

    2014-11-15

    This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe{sub 2}O{sub 3} nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe{sub 2}O{sub 3} nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe{sub 2}O{sub 3} MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe{sub 2}O{sub 3} MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe{sub 2}O{sub 3} nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (,24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe{sub 2}O{sub 3} MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G2/M phase. Fe{sub 2}O{sub 3} MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells. (author)

  1. Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

    Li, Chao; Ruan, Jing; Yang, Meng; Pan, Fei; Gao, Guo; Qu, Su; Shen, You-Lan; Dang, Yong-Jun; Wang, Kan; Jin, Wei-Lin; Cui, Da-Xiang

    2015-01-01

    Human induced pluripotent stem (iPS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human iPS cells labeled with fluorescent magnetic nanoparticles (FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Human iPS cells were prepared and cultured for 72 h. The culture medium was collected, and then was co-incubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human iPS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. iPS cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iPS cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. FMNP-labeled human iPS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer

  2. Comparison of microwave and magnetic nanoparticle hyperthermia radiosensitization in murine breast tumors

    Giustini, Andrew J.; Petryk, Alicia A.; Hoopes, Paul J.

    2011-03-01

    Hyperthermia has been shown to be an effective radiosensitizer. Its utility as a clinical modality has been limited by a minimally selective tumor sensitivity and the inability to be delivered in a tumor-specific manner. Recent in vivo studies (rodent and human) have shown that cancer cell-specific cytotoxicity can be effectively and safely delivered via iron oxide magnetic nanoparticles (mNP) and an appropriately matched noninvasive alternating magnetic field (AMF). To explore the tumor radiosensitization potential of mNP hyperthermia we used a syngeneic mouse breast cancer model, dextran-coated 110 nm hydrodynamic diameter mNP and a 169 kHz / 450 Oe (35.8 kA/m) AMF. Intradermally implanted (flank) tumors (150 +/- 40 mm3) were treated by injection of 0.04 ml mNP (7.5 mg Fe) / cm3 into the tumor and an AMF (35.8 kA/m and 169 kHz) exposure necessary to achieve a CEM (cumulative equivalent minute) thermal dose of 60 (CEM 60). Tumors were treated with mNP hyperthermia (CEM 60), radiation alone (15 Gy, single dose) and in combination. Compared to the radiation and heat alone treatments, the combined treatment resulted in a greater than two-fold increase in tumor regrowth tripling time (tumor treatment efficacy). None of the treatments resulted in significant normal tissue toxicity or morbidity. Studies were also conducted to compare the radiosensitization effect of mNP hyperthermia with that of microwave-induced hyperthermia. The effects of incubation of nanoparticles within tumors (to allow nanoparticles to be endocytosed) before application of AMF and radiation were determined. This preliminary information suggests cancer cell specific hyperthermia (i.e. antibody-directed or anatomically-directed mNP) is capable of providing significantly greater radiosensitization / therapeutic ratio enhancement than other forms of hyperthermia delivery.

  3. Magnetic Nanoparticles Coated with a Thermosensitive Polymer with Hyperthermia Properties

    Felisa Reyes-Ortega

    2017-12-01

    Full Text Available Magnetic nanoparticles (MNPs have been widely used to increase the efficacy of chemotherapeutics, largely through passive accumulation provided by the enhanced permeability and retention effect. Their incorporation into biopolymer coatings enables the preparation of magnetic field-responsive, biocompatible nanoparticles that are well dispersed in aqueous media. Here we describe a synthetic route to prepare functionalized, stable magnetite nanoparticles (MNPs coated with a temperature-responsive polymer, by means of the hydrothermal method combined with an oil/water (o/w emulsion process. The effects of both pH and temperature on the electrophoretic mobility and surface charge of these MNPs are investigated. The magnetite/polymer composition of these systems is detected by Fourier Transform Infrared Spectroscopy (FTIR and quantified by thermogravimetric analysis. The therapeutic possibilities of the designed nanostructures as effective heating agents for magnetic hyperthermia are demonstrated, and specific absorption rates as high as 150 W/g, with 20 mT magnetic field and 205 kHz frequency, are obtained. This magnetic heating response could provide a promising nanoparticle system for combined diagnostics and cancer therapy.

  4. Thermosensitive Nanostructured Media for imaging and Hyperthermia Cancer Treatment

    Martirosyan, Karen

    2011-03-01

    Hyperthermia has been used for many years to treat a wide variety of tumors in patients. The most commonly applied method of hyperthermia is capacitive heating by using microwave. Magnetic fluids based on iron oxide (Fe3O4), stabilized by biocompatible surfactants are typically used as heating agent. However, significant limitations of using commercial available magnetic particles are non-selectivity and overheating of surrounding normal tissues. To improve the efficacy of hyperthermia treatment we intend to develop Curie temperature (Tc)-tuned nanostructured media having T2 relaxation response on MRI for selective and self-controlled hyperthermia cancer treatment. As an active part of this media we fabricated superparamagnetic, biocompatible and dextran coated ferrite nanoparticles Mg1+xTixFe2(1-x)O4 at 0.3 x connected to a hydrocarbon chain, such as glycine, hydrazine, or urea. Our experiments revealed that ferrite with formula Mg1.35Ti0.35Fe1.3O4 appears with Curie temperature within 46-50rC. NSF, grant # 0933140.

  5. Simultaneous hyperthermia and doxorubicin delivery from polymer-coated magnetite nanoparticles

    Iglesias, G.R., E-mail: iglesias@ugr.es [Department of Applied Physics, University of Granada, Granada 18071 (Spain); Delgado, A.V.; González-Caballero, F. [Department of Applied Physics, University of Granada, Granada 18071 (Spain); Ramos-Tejada, M.M. [Department of Physics, University of Jaén, Linares 23700 (Spain)

    2017-06-01

    In this work, the hyperthermia response, (i.e., heating induced by an externally applied alternating magnetic field) and the simultaneous release of an anti-cancer drug (doxorubicin) by polymer-coated magnetite nanoparticles have been investigated. After describing the setup for hyperthermia measurements in suspensions of magnetic nanoparticles, the hyperthermia (represented by the rate of suspension heating and, ultimately, by the specific absorption rate or SAR) of magnetite nanoparticles (both bare and polymer-coated as drug nanocarriers) is discussed. The effect of the applied ac magnetic field on doxorubicin release is also studied, and it is concluded that the field does not interfere with the release process, demonstrating the double functionality of the investigated particles. - Highlights: • Magnetite NPs coated with polymers are used for drug delivery and hyperthermia. • The SAR of polyelectrolyte-coated NPs is larger because of their improved stability. • The antitumor drug doxorubicin is adsorbed on the coated particles. • The release rate of the drug is not affected by the ac magnetic field used in hyperthermia.

  6. Hyperthermia effects in the presence of gold nanoparticles together with chemotherapy on Saos-2 cell line

    Sazgarnia, A.; Bahreyni Toosi, M. H.; Haji Ghahremani, F.; Rajabi, O.; Aledavood, A.; Esmaily, H.

    2011-01-01

    Hyperthermia created by microwave, infrared, ultrasound and other methods, is often utilized as an adjuvant to sensitize cancer cells to the effects of chemotherapy and radiation therapy. We investigated the efficacy of hyperthermia using microwave in synergy with chemotherapy in the presence and absence and gold nanoparticles. Material and Methods: After culturing and proliferation of the Saos-2 cell line derived from human osteogenic sarcoma, the cells were incubated at two concentrations of gold nanoparticles in two diameters of 20 and 40 nm and in the absence and presence of doxorubicin in different groups. Forty eight hours after irradiating the cells with microwave up to a temperature of 42 d egree C , cell survival rate was determined using the MTT method, in order to study the effectiveness of the therapeutic parameters. Results: Cell survival in the presence of gold nanoparticles was greater than 95%. After chemotherapy by doxorubicin with and without 40 nm gold nanoparticles, cell survival rates were determined as 62.8% and 37.1 %, declining down to 17% and 4.1% respectively following the combined treatment with microwave and chemotherapy in the presence of 20 and 40 nm gold nanoparticles. Discussion and Conclusions: Gold nanoparticles did not induce any cytotoxicity by themselves; their presence along with microwave provided a reduction in survival rate that was comparable in severity with the lethal effects of doxorubicin. microwave hyperthermia with gold nanoparticles produced a higher treatment efficiency in comparison to similar groups in which gold nanoparticles were absent. The synergism observed between hyperthermia and chemotherapy was dependent in gold nanoparticles' size and concentration. This finding could be caused by increased uptake of doxorubicin by the cells in the presence of gold nanoparticles.

  7. Gelatine-assisted synthesis of magnetite nanoparticles for magnetic hyperthermia

    Alves, André F.; Mendo, Sofia G. [Universidade de Lisboa, Centro de Química e Bioquímica, Faculdade de Ciências (Portugal); Ferreira, Liliana P. [Universidade de Lisboa, Biosystems and Integrative Sciences Institute, Faculdade de Ciências (Portugal); Mendonça, Maria Helena [Universidade de Lisboa, Centro de Química e Bioquímica, Faculdade de Ciências (Portugal); Ferreira, Paula [University of Aveiro, Department of Materials and Ceramic Engineering, CICECO - Aveiro Institute of Materials (Portugal); Godinho, Margarida; Cruz, Maria Margarida [Universidade de Lisboa, Biosystems and Integrative Sciences Institute, Faculdade de Ciências (Portugal); Carvalho, Maria Deus, E-mail: mdcarvalho@ciencias.ulisboa.pt [Universidade de Lisboa, Centro de Química e Bioquímica, Faculdade de Ciências (Portugal)

    2016-01-15

    Magnetite nanoparticles were synthesized by the co-precipitation method exploring the use of gelatine and agar as additives. For comparison, magnetite nanoparticles were also prepared by standard co-precipitation, by co-precipitation with the addition of a surfactant (sodium dodecyl sulphate) and by the thermal decomposition method. The structure and morphology of the synthesized nanoparticles were investigated by powder X-ray diffraction and transmission electron microscopy. Their magnetic properties were studied by SQUID magnetometry and {sup 57}Fe Mössbauer spectroscopy. The nanoparticles potential for applications in magnetic hyperthermia was evaluated through heating efficiency under alternating magnetic field. The results show that all synthesis methods produce Fe{sub 3−x}O{sub 4} nanoparticles with similar sizes. The nanoparticles synthesized in the gelatine medium display the narrowest particle size distribution, the lowest oxidation degree, one of the highest saturation magnetization values and the best hyperthermia efficiency, proving that this gelatine-assisted synthesis is an efficient, environmental friendly, and low-cost method to produce magnetite nanoparticles. Graphical Abstract: A new gelatine-assisted method is an efficient and low-cost way to synthesize magnetite nanoparticles with enhanced magnetic hyperthermia.

  8. Photoacoustic-Based-Close-Loop Temperature Control for Nanoparticle Hyperthermia.

    Xiaohua, Feng; Fei, Gao; Yuanjin, Zheng

    2015-07-01

    Hyperthermia therapy requires tight temperature control to achieve selective killing of cancerous tissue with minimal damage on surrounding healthy tissues. To this end, accurate temperature monitoring and subsequent heating control are critical. However, an economic, portable, and real-time temperature control solution is currently lacking. To bridge this gap, we present a novel portable close-loop system for hyperthermia temperature control, in which photoacoustic technique is proposed for noninvasive real-time temperature measurement. Exploiting the high sensitivity of photoacoustics, the temperature is monitored with an accuracy of around 0.18 °C and then fed back to a controller implemented on field programmable gate array (FPGA) for temperature control. Dubbed as portable hyperthermia feedback controller (pHFC), it stabilizes the temperature at preset values by regulating the hyperthermia power with a proportional-integral-derivative (PID) algorithm; and to facilitate digital implementation, the pHFC further converts the PID output into switching values (0 and 1) with the pulse width modulation (PWM) algorithm. Proof-of-concept hyperthermia experiments demonstrate that the pHFC system is able to bring the temperature from baseline to predetermined value with an accuracy of 0.3° and a negligible temperature overshoot. The pHFC can potentially be translated to clinical applications with customized hyperthermia system design. This paper can facilitate future efforts in seamless integration of close-loop temperature control solution and various clinical hyperthermia systems.

  9. The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

    Hoopes, P. Jack; Wagner, Robert J.; Song, Ailin; Osterberg, Bjorn; Gladstone, David J.; Bursey, Alicea A.; Fiering, Steven N.; Giustini, Andrew J.

    2017-02-01

    It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

  10. Magnetic Properties of Magnetic Nanoparticles for Efficient Hyperthermia

    Ihab M. Obaidat

    2015-01-01

    Full Text Available Localized magnetic hyperthermia using magnetic nanoparticles (MNPs under the application of small magnetic fields is a promising tool for treating small or deep-seated tumors. For this method to be applicable, the amount of MNPs used should be minimized. Hence, it is essential to enhance the power dissipation or heating efficiency of MNPs. Several factors influence the heating efficiency of MNPs, such as the amplitude and frequency of the applied magnetic field and the structural and magnetic properties of MNPs. We discuss some of the physics principles for effective heating of MNPs focusing on the role of surface anisotropy, interface exchange anisotropy and dipolar interactions. Basic magnetic properties of MNPs such as their superparamagnetic behavior, are briefly reviewed. The influence of temperature on anisotropy and magnetization of MNPs is discussed. Recent development in self-regulated hyperthermia is briefly discussed. Some physical and practical limitations of using MNPs in magnetic hyperthermia are also briefly discussed.

  11. Terbium doped SnO2 nanoparticles as white emitters and SnO2:5Tb/Fe3O4 magnetic luminescent nanohybrids for hyperthermia application and biocompatibility with HeLa cancer cells.

    Singh, Laishram Priyobarta; Singh, Ningthoujam Premananda; Srivastava, Sri Krishna

    2015-04-14

    SnO2:5Tb (SnO2 doped with 5 at% Tb(3+)) nanoparticles were synthesised by a polyol method and their luminescence properties at different annealing temperatures were studied. Characterization of nanomaterials was done by X-ray diffraction (XRD), Fourier transformation infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and vibrating sample magnetometry (VSM). XRD studies indicate that the prepared nanoparticles were of tetragonal structures. Upon Tb(3+) ion incorporation into SnO2, Sn(4+) changes to Sn(2+) and, on annealing again at higher temperature, Sn(2+) changes to Sn(4+). The prepared nanoparticles were spherical in shape. Sn-O vibrations were found from the FTIR studies. In photoluminescence studies, the intensity of the emission peaks of Tb(3+) ions increases with the increase of annealing temperature, and emission spectra lie in the region of white emission in the CIE diagram. CCT calculations show that the SnO2:5Tb emission lies in cold white emission. Quantum yields up to 38% can be obtained for 900 °C annealed samples. SnO2:5Tb nanoparticles were well incorporated into the PVA polymer and such a material incorporated into the polymer can be used for display devices. The SnO2:5Tb/Fe3O4 nanohybrid was prepared and investigated for hyperthermia applications at different concentrations of the nanohybrid. This achieves a hyperthermia temperature (42 °C) under an AC magnetic field. The hybrid nanomaterial SnO2:5Tb/Fe3O4 was found to exhibit biocompatibility with HeLa cells (human cervical cancer cells) at concentrations up to 74% for 100 μg L(-1). Also, this nanohybrid shows green emission and thus it will be helpful in tracing magnetic nanoparticles through optical imaging in vivo and in vitro application.

  12. Preparation of Multifunctional Fe@Au Core-Shell Nanoparticles with Surface Grafting as a Potential Treatment for Magnetic Hyperthermia

    Ren-Jei Chung

    2014-01-01

    Full Text Available Iron core gold shell nanoparticles grafted with Methotrexate (MTX and indocyanine green (ICG were synthesized for the first time in this study, and preliminarily evaluated for their potential in magnetic hyperthermia treatment. The core-shell Fe@Au nanoparticles were prepared via the microemulsion process and then grafted with MTX and ICG using hydrolyzed poly(styrene-alt-maleic acid (PSMA to obtain core-shell Fe@Au-PSMA-ICG/MTX nanoparticles. MTX is an anti-cancer therapeutic, and ICG is a fluorescent dye. XRD, TEM, FTIR and UV-Vis spectrometry were performed to characterize the nanoparticles. The data indicated that the average size of the nanoparticles was 6.4 ± 09 nm and that the Au coating protected the Fe core from oxidation. MTX and ICG were successfully grafted onto the surface of the nanoparticles. Under exposure to high frequency induction waves, the superparamagnetic nanoparticles elevated the temperature of a solution in a few minutes, which suggested the potential for an application in magnetic hyperthermia treatment. The in vitro studies verified that the nanoparticles were biocompatible; nonetheless, the Fe@Au-PSMA-ICG/MTX nanoparticles killed cancer cells (Hep-G2 via the magnetic hyperthermia mechanism and the release of MTX.

  13. Preparation of Multifunctional Fe@Au Core-Shell Nanoparticles with Surface Grafting as a Potential Treatment for Magnetic Hyperthermia.

    Chung, Ren-Jei; Shih, Hui-Ting

    2014-01-24

    Iron core gold shell nanoparticles grafted with Methotrexate (MTX) and indocyanine green (ICG) were synthesized for the first time in this study, and preliminarily evaluated for their potential in magnetic hyperthermia treatment. The core-shell Fe@Au nanoparticles were prepared via the microemulsion process and then grafted with MTX and ICG using hydrolyzed poly(styrene-alt-maleic acid) (PSMA) to obtain core-shell Fe@Au-PSMA-ICG/MTX nanoparticles. MTX is an anti-cancer therapeutic, and ICG is a fluorescent dye. XRD, TEM, FTIR and UV-Vis spectrometry were performed to characterize the nanoparticles. The data indicated that the average size of the nanoparticles was 6.4 ± 09 nm and that the Au coating protected the Fe core from oxidation. MTX and ICG were successfully grafted onto the surface of the nanoparticles. Under exposure to high frequency induction waves, the superparamagnetic nanoparticles elevated the temperature of a solution in a few minutes, which suggested the potential for an application in magnetic hyperthermia treatment. The in vitro studies verified that the nanoparticles were biocompatible; nonetheless, the Fe@Au-PSMA-ICG/MTX nanoparticles killed cancer cells (Hep-G2) via the magnetic hyperthermia mechanism and the release of MTX.

  14. Biodegradable magnesium nanoparticle-enhanced laser hyperthermia therapy

    Wang Q

    2012-08-01

    Full Text Available Qian Wang,1 Liping Xie,1 Zhizhu He,2 Derui Di,2 Jing Liu1,21Department of Biomedical Engineering, School of Medicine, Tsinghua University, 2Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, People's Republic of ChinaBackground: Recently, nanoparticles have been demonstrated to have tremendous merit in terms of improving the treatment specificity and thermal ablation effect on tumors. However, the potential toxicity and long-term side effects caused by the introduced nanoparticles and by expelling them out of the body following surgery remain a significant challenge. Here, we propose for the first time to directly adopt magnesium nanoparticles as the heating enhancer in laser thermal ablation to avoid these problems by making full use of the perfect biodegradable properties of this specific material.Methods: To better understand the new nano “green” hyperthermia modality, we evaluated the effects of magnesium nanoparticles on the temperature transients inside the human body subject to laser interstitial heating. Further, we experimentally investigated the heating enhancement effects of magnesium nanoparticles on a group of biological samples: oil, egg white, egg yolk, in vitro pig tissues, and the in vivo hind leg of rabbit when subjected to laser irradiation.Results: Both the theoretical simulations and experimental measurements demonstrated that the target tissues injected with magnesium nanoparticles reached much higher temperatures than tissues without magnesium nanoparticles. This revealed the enhancing behavior of the new nanohyperthermia method.Conclusion: Given the unique features of magnesium nanoparticles – their complete biological safety and ability to enhance heating – which most other advanced metal nanoparticles do not possess, the use of magnesium nanoparticles in hyperthermia therapy offers an important “green” nanomedicine modality for treating tumors

  15. Hyperthermia

    Perez, C.A.; Emami, B.; Nussbaum, G.; Sapareto, S.

    1987-01-01

    The effect on heat on malignant tumors was first reported by Hippocrates. In 1856 another described the disappearance of a soft tissue sarcoma following high fever in a patient with erysipelas. Later, another induced fever by injecting bacterial toxins, and others used localized hyperthermia to produce tumor regression in patients. There were 32 patients with advanced cancer of various types treated with a combination of heat, induced with pyrogenic substances, and x-ray therapy. Twenty-nine of these patients improved for 1 to 6 months. In the past 10 years interest has been rekindled to the clinical application of this modality because numerous papers have indicated that there may be a significant advantage to the use of heat alone or combined with irradiation and cytotoxic drugs to enhance the killing of tumor cells. The clinical use of heat has been hampered by a lack of adequate equipment to deliver effective heat in deep-seated lesions and of thermometry techniques that provide reliable information on heat distribution in target tissues. However, significant progress has been made. About 30% to 50% of patients with solid tumors have recurrences at the primary site. Many of these patients have regional lymph node recurrences. Both failure patterns could be improved if effective radiation sensitizers are developed

  16. Effect of SPIO Nanoparticle Concentrations on Temperature Changes for Hyperthermia via MRI

    Alsayed A. M. Elsherbini

    2013-01-01

    Full Text Available Magnetic nanoparticles (MNPs are being developed for a wide range of biomedical applications. In particular, hyperthermia involves heating the MNPs through exposure to an alternating magnetic field (AMF. These materials offer the potential for selectively by heating cancer tissue locally and at the cellular level. This may be a successful method if there are enough particles in a tumor possessing sufficiently high specific absorption rate (SAR to deposit heat quickly while minimizing thermal damage to surrounding tissue. The current research aim is to study the influence of super paramagnetic iron oxides Fe3O4 (SPIO NPs concentration on the total heat energy dose and the rate of temperature change in AMF to induce hyperthermia in Ehrlich carcinoma cells implanted in female mice. The results demonstrated a linearly increasing trend between these two factors.

  17. Precise determination of the heat delivery during in vivo magnetic nanoparticle hyperthermia with infrared thermography

    Rodrigues, Harley F.; Capistrano, Gustavo; Mello, Francyelli M.; Zufelato, Nicholas; Silveira-Lacerda, Elisângela; Bakuzis, Andris F.

    2017-05-01

    Non-invasive and real-time monitoring of the heat delivery during magnetic nanoparticle hyperthermia (MNH) is of fundamental importance to predict clinical outcomes for cancer treatment. Infrared thermography (IRT) can determine the surface temperature due to three-dimensional heat delivery inside a subcutaneous tumor, an argument that is supported by numerical simulations. However, for precise temperature determination, it is of crucial relevance to use a correct experimental configuration. This work reports an MNH study using a sarcoma 180 murine tumor containing 3.9 mg of intratumorally injected manganese-ferrite nanoparticles. MNH was performed at low field amplitude and non-uniform field configuration. Five 30 min in vivo magnetic hyperthermia experiments were performed, monitoring the surface temperature with a fiber optical sensor and thermal camera at distinct angles with respect to the animal’s surface. The results indicate that temperature errors as large as 7~\\circ C can occur if the experiment is not properly designed. A new IRT error model is found to explain the data. More importantly, we show how to precisely monitor temperature with IRT during hyperthermia, which could positively impact heat dosimetry and clinical planning.

  18. Current Status and Perspectives of Hyperthermia in Cancer Therapy

    Hiraoka, Masahiro; Nagata, Yasushi; Mitsumori, Michihide; Sakamoto, Masashi; Masunaga, Shin-ichiro

    2004-08-01

    Clinical trials of hyperthermia in combination with radiation therapy or chemotherapy undertaken over the past decades in Japan have been reviewed. Originally developed heating devices were mostly used for these trials, which include RF (radiofrequency) capacitive heating devices, a microwave heating device with a lens applicator, an RF intracavitary heating device, an RF current interstitial heating device, and ferromagnetic implant heating device. Non-randomized trials for various cancers, demonstrated higher response rate in thermoradiotherapy than in radiotherapy alone. Randomized trials undertaken for esophageal cancers also demonstrated improved local response with the combined use of hyperthermia. Furthermore, the complications associated with treatment were not generally serious. These clinical results indicate the benefit of combined treatment of hyperthermia and radiotherapy for various malignancies. On the other hand, the presently available heating devices are not satisfactory from the clinical viewpoints. With the advancement of heating and thermometry technologies, hyperthermia will be more widely and safely used in the treatment of cancers.

  19. Physics responsible for heating efficiency and self-controlled temperature rise of magnetic nanoparticles in magnetic hyperthermia therapy.

    Shaterabadi, Zhila; Nabiyouni, Gholamreza; Soleymani, Meysam

    2018-03-01

    Magnetic nanoparticles as heat-generating nanosources in hyperthermia treatment are still faced with many drawbacks for achieving sufficient clinical potential. In this context, increase in heating ability of magnetic nanoparticles in a biologically safe alternating magnetic field and also approach to a precise control on temperature rise are two challenging subjects so that a significant part of researchers' efforts has been devoted to them. Since a deep understanding of Physics concepts of heat generation by magnetic nanoparticles is essential to develop hyperthermia as a cancer treatment with non-adverse side effects, this review focuses on different mechanisms responsible for heat dissipation in a radio frequency magnetic field. Moreover, particular attention is given to ferrite-based nanoparticles because of their suitability in radio frequency magnetic fields. Also, the key role of Curie temperature in suppressing undesired temperature rise is highlighted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Self-regulated magnetic fluid hyperthermia: A potential cancer therapy

    Bagaria, Hitesh Ghanshyam

    An emerging cancer therapy, self-regulated magnetic fluid hyperthermia (MFH), is the motivation for this work. In this therapy, cancer is annihilated by heating the tumor to desired therapeutic temperatures (˜45°C) by using magnetic nanoparticles of controlled Curie temperatures (Tc). This work was aimed at preparing and characterizing FePt, NiPd and NiPt nanoparticles for self-regulated MFH because their Tc could be tuned by changing their composition. Based on the excellent colloidal stability, size tunability and toxicity considerations, FePt was an obvious choice for self-regulated MFH. The 3.2 nm Fe61Pt39 particles displayed a Tc of 151°C, which is well below the Tc of bulk Fe61Pt39 (˜327°C). To reach the desired Tc of 45°C the composition of iron needs to be increased. However, a major obstacle was the formation of iron oxide shells with increase in iron composition of the particles. A recent finding that the composition of individual FePt particles deviated significantly from the average value encouraged us to study the mechanism of formation of FePt particles. Our analysis showed that early in the reaction the particles were Pt-rich and as the reaction proceeded the Fe content increased. It was found that the wide distribution in the composition of individual particles started early in the synthesis, suggesting that the compositional variability may be attributed to the Pt nuclei. The synthesized FePt particles are unsuitable for biological applications because of their hydrophobic surface. Hence, their surface was modified by ligand exchange with mercapto alkanoic acids. After ligand exchange, stable FePt dispersions could be formed in alkaline water. The study revealed that both the carboxylate and thiol groups were required to form stable FePt dispersions. In addition, 15 nm gold particles were successfully conjugated to genetically modified adenoviruses that selectively bind to cancer tumors. We also modeled the thermal transport in tissues during

  1. Feasibility study of local ultrasound hyperthermia in cancer therapy

    Jones, K.G.; Straube, W.; Emami, B.; Perez, C.A.

    1987-01-01

    This paper describes a retrospective analysis of patients treated at Washington University for recurrent or persistent cancer with Ultrasound Hyperthermia between October 1984 and June 1986. Fifteen of 102 lesions were treated during this time period with Ultrasound Hyperthermia instead of microwave hyperthermia due to the size of the lesion needing heat at depths greater than 4 cm. Also, the patients' lesion could not be implanted for interstitial microwave hyperthermia. Fourteen of the treated patients received concomitant radiotherapy, while one received concomitant Bleomycin. There were 79 total hyperthermia treatments delivered, of which 67 achieved a therapeutic temperature of 43 0 C for 60 minutes. During 15/79 treatments, patients experienced pain; of which 11/15 lead to poor heating. Only one treatment of the twelve poor treatments was secondary to technical difficulties. Complete local control was accomplished in seven patients, a partial response in four patients. The results of therapeutic heating and its relationship to the site of treatment and local control are presented, along with phantom studies of Ultrasound microwave hyperthermia reemphasizing the feasibility of using Ultrasound Hyperthermia

  2. Targeting therapy-resistant cancer stem cells by hyperthermia

    Oei, A L; Vriend, L E M; Krawczyk, P M

    2017-01-01

    Eradication of all malignant cells is the ultimate but challenging goal of anti-cancer treatment; most traditional clinically-available approaches fail because there are cells in a tumour that either escape therapy or become therapy-resistant. A subpopulation of cancer cells, the cancer stem cells...... are limited. Here, we argue that hyperthermia - a therapeutic approach based on local heating of a tumour - is potentially beneficial for targeting CSCs in solid tumours. First, hyperthermia has been described to target cells in hypoxic and nutrient-deprived tumour areas where CSCs reside and ionising...

  3. Magnetic nanoparticles for cancer therapy

    Bakuzis, Andris F.

    2014-01-01

    Full text: Magnetic nanoparticles have been used in several biomedical applications, spanning from cell separation, early diagnosis of metastasis to even the treatment of cancer via magnetic hyperthermia (MH). This last technique consists in the increase of temperature of nanoparticles when their magnetic moments interact with a magnetic alternating field. This effect has been suggested as an innovative therapy to cancer treatment, due to the delivery of heat or therapeutic agents, such as drugs, genes, and others. In addition, several clinical studies has demonstrated synergetic effects between hyperthermia and radiotherapy [1]. This indicates a great therapeutic potential for this noninvasive and targeted technique. In this talk we will discuss results from the literature and from our own group in the treatment of cancer via magnetic hyperthermia. Several types of magnetic nanoparticles suggested for this application will be discussed, as well as the historical evolution of this procedure, which although suggested in the late 50' only recently was approved in Europe for treatment of humans with brain tumors. (author) [pt

  4. Recommendations for In Vitro and In Vivo Testing of Magnetic Nanoparticle Hyperthermia Combined with Radiation Therapy

    Spiridon V. Spirou

    2018-05-01

    Full Text Available Magnetic nanoparticle (MNP-mediated hyperthermia (MH coupled with radiation therapy (RT is a novel approach that has the potential to overcome various practical difficulties encountered in cancer treatment. In this work, we present recommendations for the in vitro and in vivo testing and application of the two treatment techniques. These recommendations were developed by the members of Working Group 3 of COST Action TD 1402: Multifunctional Nanoparticles for Magnetic Hyperthermia and Indirect Radiation Therapy (“Radiomag”. The purpose of the recommendations is not to provide definitive answers and directions but, rather, to outline those tests and considerations that a researcher must address in order to perform in vitro and in vivo studies. The recommendations are divided into 5 parts: (a in vitro evaluation of MNPs; (b in vitro evaluation of MNP-cell interactions; (c in vivo evaluation of the MNPs; (d MH combined with RT; and (e pharmacokinetic studies of MNPs. Synthesis and characterization of the MNPs, as well as RT protocols, are beyond the scope of this work.

  5. Radiation therapy combined with hyperthermia in advanced cancer

    Okuma, Akiko; Terashima, Hiromi; Torii, Yoshikuni; Nakata, Hajime; Inatomi, Hisato

    1986-01-01

    Radiation therapy combined with radiofrequency (RF) hyperthermia was performed on 5 advanced cancer patients. Included were one each with urinary bladder cancer, hepatoma with left axillary node metastasis, breast cancer, tongue cancer with left cervical metastasis, and mandibular cancer. All had large tumors, which were judged to be uncontrollable by radiotherapy alone. They were treated with irradiation (Linac: 10 MV X-ray 1.8 - 2.0 Gy/day, 5 days/week), followed within an hour by RF hyperthermia once or twice a week. Partial response was obtained in the urinary bladder cancer patient. Surface overheating around the margin of electrodes occurred in all but no severe complications were observed. (author)

  6. Preparation and characterization of composite microspheres for brachytherapy and hyperthermia treatment of cancer

    Zhao Di; Huang Wenhai; Rahaman, Mohamed N.; Day, Delbert E.; Wang Deping; Gu Yifei

    2012-01-01

    Composite microspheres were prepared by coating yttrium–aluminum–silicate (YAS) glass microspheres (20–30 μm) with a layer of Fe 3 O 4 nanoparticles and evaluated for potential use in brachytherapy and hyperthermia treatment of cancer. After neutron activation to form the β-emitting 90 Y radionuclide, the composite microspheres can be injected into a patient to destroy cancerous tumors; at the same time, the composite microspheres can generate heat upon application of a magnetic field to also destroy the tumors. The results showed that the composite microspheres were chemically durable when immersed in a simulated body fluid (SBF), with ∼ 0.25% weight loss and ∼ 3.2% yttrium dissolved into the SBF after 30 days at 37 °C. The composite microspheres also showed ferromagnetic properties as a result of the Fe 3 O 4 coating; when immersed in water at 20 °C (20 mg in 1 mL of water), the application of an alternating magnetic field produced a temperature increase from 20 °C to 38−46 °C depending on the thickness of the Fe 3 O 4 coating. The results indicate that these composite microspheres have promising potential in combined brachytherapy and hyperthermia treatment of cancerous tumors. - Highlights: ► Composite microspheres for brachytherapy and hyperthermia treatment of cancer. ► Fe 3 O 4 nanoparticles coated on the yttrium–aluminum–silicate glass microspheres. ► Microspheres are chemically stable in SBF. ► Microspheres can generate heat for hyperthermia under an alternating magnetic field. ► Microspheres can emit β-rays for brachytherapy after neutron activation.

  7. Predicting thermal history a-priori for magnetic nanoparticle hyperthermia of internal carcinoma

    Dhar, Purbarun; Sirisha Maganti, Lakshmi

    2017-08-01

    This article proposes a simplistic and realistic method where a direct analytical expression can be derived for the temperature field within a tumour during magnetic nanoparticle hyperthermia. The approximated analytical expression for thermal history within the tumour is derived based on the lumped capacitance approach and considers all therapy protocols and parameters. The present method is simplistic and provides an easy framework for estimating hyperthermia protocol parameters promptly. The model has been validated with respect to several experimental reports on animal models such as mice/rabbit/hamster and human clinical trials. It has been observed that the model is able to accurately estimate the thermal history within the carcinoma during the hyperthermia therapy. The present approach may find implications in a-priori estimation of the thermal history in internal tumours for optimizing magnetic hyperthermia treatment protocols with respect to the ablation time, tumour size, magnetic drug concentration, field strength, field frequency, nanoparticle material and size, tumour location, and so on.

  8. Biological effects of hyperthermia

    Okumura, Hiroshi

    1980-01-01

    Biological effects of hyperthermia and application of hyperthermia to cancer therapy were outlined. As to independent effects of hyperthermia, heat sensitivity of cancer cells, targets of hyperthermia, thermal tolerance of cancer cells, effects of pH on hyperthermic cell survival, effects of hyperthermia on normal tissues, and possibility of clinical application of hyperthermia were described. Combined effect of hyperthermia and x-irradiation to enhance radiosensitivity of cancer cells, its mechanism, effects of oxygen on cancer cells treated with hyperthermia and irradiation, and therapeutic ratio of combined hyperthermia and irradiation were also described. Finally, sensitizers were mentioned. (Tsunoda, M.)

  9. Bi-functional properties of Fe3O4@YPO4:Eu hybrid nanoparticles: hyperthermia application.

    Prasad, A I; Parchur, A K; Juluri, R R; Jadhav, N; Pandey, B N; Ningthoujam, R S; Vatsa, R K

    2013-04-14

    Magnetic nanoparticles based hyperthermia therapy is a possible low cost and effective technique for killing cancer tissues in the human body. Fe3O4 and Fe3O4@YPO4:5Eu hybrid magnetic nanoparticles are prepared by co-precipitation method and their average particle sizes are found to be ∼10 and 25 nm, respectively. The particles are spherical, non-agglomerated and highly dispersible in water. The crystallinity of as-prepared YPO4:5Eu sample is more than Fe3O4@YPO4:5Eu hybrid magnetic nanoparticles. The chemical bonds interaction between Fe3O4 and YPO4:5Eu is confirmed through FeO-P. The magnetization of hybrid nanocomposite shows magnetization Ms = 11.1 emu g(-1) with zero coercivity (measured at 2 × 10(-4) Oe) at room temperature indicating superparamagnetic behaviour. They attain hyperthermia temperature (~42 °C) under AC magnetic field showing characteristic induction heating of the prepared nanohybrid and they will be potential material for biological application. Samples produce the red emission peaks at 618 nm and 695 nm, which are in range of biological window. The quantum yield of YPO4:5Eu sample is found to be 12%. Eu(3+) present on surface and core could be distinguished from luminescence decay study. Very high specific absorption rate up to 100 W g(-1) could be achieved. The intracellular uptake of nanocomposites is found in mouse fibrosarcoma (Wehi 164) tumor cells by Prussian blue staining.

  10. Stabilization of temperature during magnetic hyperthermia by Ce substituted magnetite nanoparticles

    Shaw, S.K.; Alla, S.K. [Department of Metallurgical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005 (India); Meena, S.S. [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Mandal, R.K. [Department of Metallurgical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005 (India); Prasad, N.K., E-mail: nandkp.met@iitbhu.ac.in [Department of Metallurgical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005 (India)

    2017-07-15

    Highlights: • Ce{sub x}Fe{sub 3−x}O{sub 4} (0.01 ≤ x ≤ 0.5) nanoparticles below 15 nm were synthesized by microwave refluxing method. • The saturation magnetization decreased with increased Ce concentration. • The sample displayed stabilization of temperature near 42 °C during magnetic hyperthermia. - Abstract: We report here magnetic hyperthermia using nanoparticles of Ce{sub x}Fe{sub 3−x}O{sub 4} (x = 0.01, 0.05, 0.1, 0.3 and 0.5) during which temperature was found to be stabilizing near 42 °C. This happens despite of their high saturation magnetization (M{sub S}) and Curie temperature (T{sub C}) values. It was observed that by selecting an appropriate magnetic field the temperature can be rose exactly near the therapeutic temperature and thus it will help to selectively kill the cancerous cells leaving normal cells unaffected. These nanoparticles (size around 8–15 nm) were produced by single step microwave refluxing technique. X-ray diffraction (XRD) analysis demonstrates that samples were essentially single phase except for x = 0.5 sample. The X-ray photoelectron spectroscopy (XPS) study for the samples demonstrated that Ce was present in both Ce{sup 3+} and Ce{sup 4+} states. The saturation magnetization value of the samples decreased sharply from 62 Am{sup 2}/kg for x = 0.01 to 19 Am{sup 2}/kg for x = 0.1. This value further decreased with increased Ce doping.

  11. Identification of infusion strategy for achieving repeatable nanoparticle distribution and quantification of thermal dosage using micro-CT Hounsfield unit in magnetic nanoparticle hyperthermia.

    LeBrun, Alexander; Joglekar, Tejashree; Bieberich, Charles; Ma, Ronghui; Zhu, Liang

    2016-01-01

    The objective of this study was to identify an injection strategy leading to repeatable nanoparticle deposition patterns in tumours and to quantify volumetric heat generation rate distribution based on micro-CT Hounsfield unit (HU) in magnetic nanoparticle hyperthermia. In vivo animal experiments were performed on graft prostatic cancer (PC3) tumours in immunodeficient mice to investigate whether lowering ferrofluid infusion rate improves control of the distribution of magnetic nanoparticles in tumour tissue. Nanoparticle distribution volume obtained from micro-CT scan was used to evaluate spreading of the nanoparticles from the injection site in tumours. Heating experiments were performed to quantify relationships among micro-CT HU values, local nanoparticle concentrations in the tumours, and the ferrofluid-induced volumetric heat generation rate (q(MNH)) when nanoparticles were subject to an alternating magnetic field. An infusion rate of 3 µL/min was identified to result in the most repeatable nanoparticle distribution in PC3 tumours. Linear relationships have been obtained to first convert micro-CT greyscale values to HU values, then to local nanoparticle concentrations, and finally to nanoparticle-induced q(MNH) values. The total energy deposition rate in tumours was calculated and the observed similarity in total energy deposition rates in all three infusion rate groups suggests improvement in minimising nanoparticle leakage from the tumours. The results of this study demonstrate that micro-CT generated q(MNH) distribution and tumour physical models improve predicting capability of heat transfer simulation for designing reliable treatment protocols using magnetic nanoparticle hyperthermia.

  12. Thermometric analysis of intra-cavitary hyperthermia for esophageal cancer.

    Qi, C; Li, D J

    1999-01-01

    Thermometric analysis was carried out in 51 patients with esophageal cancer treated with intra-cavitary hyperthermia combined with radio chemotherapy, to test whether temperature index (T20, T50) and T90) could be used as an indicator for tumour control. Hyperthermia was administered by intra-cavitary microwave applicator. The T20, T50 and T90 were deducted from the temperature sensors T0 and T3 situated at the center of the tumour surface and 3cm from it. Eighteen patients with local control > or =36 months were named long term control patients (LC), 24 patients with local recurrence within 24 months (LR) (there were no events occurring between 24 and 36 months) and nine patients died of metastasis without local recurrence (DM). The overall survival rates were 80.4 +/- 5.6% at 1 year, 38.3 +/- 6.9% at 3 years and 31 +/- 6.7% at 5 years, respectively. Chi-square test showed no influence of the number of hyperthermia sessions on the local control (p > 0.25). The 5-year local control rate was 18.8% for the patients with T90 or = 43 degrees C (p < 0.01). The average T90 was 43.76 +/- 0.74 degrees C for the LC patients and 43.17 +/- 0.57 degrees C for those LR (p = 0.024). The mean T90 was higher than 43 degrees C in 94.4% of LC, whereas in 58.8% of LR. The study suggested that T90 was a good parameter for thermal dose in the intracavitary hyperthermia for the treatment of esophageal cancer.

  13. Multimodal treatment combining chemotherapy, hyperthermia and radiotherapy for ovarian cancer

    Nagashima, Kei

    1992-01-01

    There has been increasing interest in the use of heat in the treatment of cancer. Theoretically cells are the most sensitive to ionizing radiation at mitosis, whereas the cycle phase that is the most resistant to ionizing radiation namely late in the DNA. Synthetic phase (late S) is the most sensitive to hyperthermia. Hyperthermia has been reported to enhance the cytocidal effects of several active chemotherapeutic agents. When thermal potentiation of chemotherapeutic agents against malignant cells is contemplated, normal tissues have a relatively high ambient blood flow which increases in response to thermal stress, thereby dissipating heat, compared to tumors. Tumors, with relatively poor blood flow and a responsive neovasculature, are in capable of augmenting flow and acting as a heat reservoir. This is the phenomenon of a heat reservoir which is one factor to enhance the cytocidal effects of several active anticancer agents for enhancing the uptake in tumor. The importance is in the adjuvant chemotherapy treated for post operative, advanced and recurrent ovarian cancer. Heating enhances the effects of radiotherapy and chemotherapy. Thirty patients with ovarian cancer were subjected to the multidisciplinary treatment with combination of hyperthermochemotherapy and radiation. The 30 patients consisted of 18 with endometrioid adenocarcinoma and 7 with serious post operative or recurrent status. Two types of equipments with rediofrequencies of 70 MHz (BSD-1000) or 434 MHZ (TAG MED·HS 434) were used for hyperthermia. Chemotherapeutic agents such as adriamycin, cis DDP, cyclophosphamide and etoposide were injected intravenously. Arterial infusion with reservoir was very effective in advanced stage of ovarian cancer. No severe or fatal side effects were observed. Hyperthermochemotherapy is useful and effective for the postoperative management or the treatment of recurrent cancer of the ovary. (J.P.N.)

  14. Model for hyperthermia with arrays of magnetic nanoparticles: spatial and time temperature distributions in tumor

    Zablotskyy, Vitaliy A.; Lunov, O.; Gómez-Polo, C.

    2010-01-01

    Roč. 10, č. 2 (2010), 690-695 ISSN 1533-4880 Institutional research plan: CEZ:AV0Z10100520 Keywords : interstitial hyperthermia * thermometry * magnetic nanoparticles * radiotherapy Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.351, year: 2010

  15. Targeted Magnetic Hyperthermia for Lung Cancer

    2014-11-01

    1171:583- 590 . 32. Colell, A., Ricci, J.E., Tait, S., Milasta, S., Maurer, U., Bouchier-Hayes, L., Fitzgerald, P., Guio-Carrion, A., Waterhouse, N.J...and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nat Biotechnol 2008;26(1):83e90. [7] Lee H, Lee E, Kim do K, Jang NK, Jeong

  16. Targeting to carcinoma cells with chitosan- and starch-coated magnetic nanoparticles for magnetic hyperthermia.

    Kim, Dong-Hyun; Kim, Kyoung-Nam; Kim, Kwang-Mahn; Lee, Yong-Keun

    2009-01-01

    The delivery of hyperthermic thermoseeds to a specific target site with minimal side effects is an important challenge in targeted hyperthermia, which employs magnetic method and functional polymers. An external magnetic field is used to control the site-specific targeting of the magnetic nanoparticles. Polymer-coated magnetic nanoparticles can confer a higher affinity to the biological cell membranes. In this study, uncoated, chitosan-coated, and starch-coated magnetic nanoparticles were synthesized for use as a hyperthermic thermoseed. Each sample was examined with respect to their applications to hyperthermia using XRD, VSM, and FTIR. In addition, the temperature changes under an alternating magnetic field were observed. As in vitro tests, the magnetic responsiveness of chitosan- and starch-coated magnetite was determined by a simple blood vessel model under various intensities of magnetic field. L929 normal cells and KB carcinoma cells were used to examine the cytotoxicity and affinity of each sample using the MTT method. The chitosan-coated magnetic nanoparticles generated a higher DeltaT of 23 degrees C under an AC magnetic field than the starch-coated magnetite, and the capturing rate of the particles was 96% under an external magnetic field of 0.4 T. The highest viability of L929 cells was 93.7%. Comparing the rate of KB cells capture with the rate of L929 cells capture, the rate of KB cells capture relatively increased with 10.8% in chitosan-coated magnetic nanoparticles. Hence, chitosan-coated magnetic nanoparticles are biocompatible and have a selective affinity to KB cells. The targeting of magnetic nanoparticles in hyperthermia was improved using a controlled magnetic field and a chitosan-coating. Therefore, chitosan-coated magnetic nanoparticles are expected to be promising materials for use in magnetic targeted hyperthermia. 2008 Wiley Periodicals, Inc.

  17. Iron oxide nanoparticles stabilized with a bilayer of oleic acid for magnetic hyperthermia and MRI applications

    Soares, Paula I.P. [i3N/CENIMAT, Department of Materials Science, Faculty of Science and Technology, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica (Portugal); Laia, César A.T. [Laboratório Associado para a Química Verde (LAQV), REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, FCT, Universidade Nova de Lisboa, 2829-516 Caparica (Portugal); Carvalho, Alexandra [i3N/CENIMAT, Department of Materials Science, Faculty of Science and Technology, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica (Portugal); Pereira, Laura C.J.; Coutinho, Joana T. [C2TN, Instituto Superior Técnico, Universidade de Lisboa, Estrada Nacional 10, ao km 139,7, 2695-066 Bobadela LRS (Portugal); Ferreira, Isabel M.M., E-mail: imf@fct.unl.pt [i3N/CENIMAT, Department of Materials Science, Faculty of Science and Technology, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica (Portugal); Novo, Carlos M.M. [Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, IHMT/UNL, 1349-008 Lisboa (Portugal); Borges, João Paulo, E-mail: jpb@fct.unl.pt [i3N/CENIMAT, Department of Materials Science, Faculty of Science and Technology, Universidade NOVA de Lisboa, Campus de Caparica, 2829-516 Caparica (Portugal)

    2016-10-15

    Highlights: • Superparamagnetic iron oxide nanoparticles were stabilized with oleic acid. • Maximum stabilization was achieved at neutral pH. • Magnetic resonance imaging and magnetic hyperthermia applications were tested. • The produced nanoparticles are viable for both biomedical applications. - Abstract: Iron oxide nanoparticles (Fe{sub 3}O{sub 4}, IONPs) are promising candidates for several biomedical applications such as magnetic hyperthermia and as contrast agents for magnetic resonance imaging (MRI). However, their colloidal stability in physiological conditions hinders their application requiring the use of biocompatible surfactant agents. The present investigation focuses on obtaining highly stable IONPs, stabilized by the presence of an oleic acid bilayer. Critical aspects such as oleic acid concentration and pH were optimized to ensure maximum stability. NPs composed of an iron oxide core with an average diameter of 9 nm measured using transmission electron microscopy (TEM) form agglomerates with an hydrodynamic diameter of around 170 nm when dispersed in water in the presence of an oleic acid bilayer, remaining stable (zeta potential of −120 mV). Magnetic hyperthermia and the relaxivities measurements show high efficiency at neutral pH which enables their use for both magnetic hyperthermia and MRI.

  18. Iron oxide nanoparticles stabilized with a bilayer of oleic acid for magnetic hyperthermia and MRI applications

    Soares, Paula I.P.; Laia, César A.T.; Carvalho, Alexandra; Pereira, Laura C.J.; Coutinho, Joana T.; Ferreira, Isabel M.M.; Novo, Carlos M.M.; Borges, João Paulo

    2016-01-01

    Highlights: • Superparamagnetic iron oxide nanoparticles were stabilized with oleic acid. • Maximum stabilization was achieved at neutral pH. • Magnetic resonance imaging and magnetic hyperthermia applications were tested. • The produced nanoparticles are viable for both biomedical applications. - Abstract: Iron oxide nanoparticles (Fe_3O_4, IONPs) are promising candidates for several biomedical applications such as magnetic hyperthermia and as contrast agents for magnetic resonance imaging (MRI). However, their colloidal stability in physiological conditions hinders their application requiring the use of biocompatible surfactant agents. The present investigation focuses on obtaining highly stable IONPs, stabilized by the presence of an oleic acid bilayer. Critical aspects such as oleic acid concentration and pH were optimized to ensure maximum stability. NPs composed of an iron oxide core with an average diameter of 9 nm measured using transmission electron microscopy (TEM) form agglomerates with an hydrodynamic diameter of around 170 nm when dispersed in water in the presence of an oleic acid bilayer, remaining stable (zeta potential of −120 mV). Magnetic hyperthermia and the relaxivities measurements show high efficiency at neutral pH which enables their use for both magnetic hyperthermia and MRI.

  19. Hysteresis losses and specific absorption rate measurements in magnetic nanoparticles for hyperthermia applications.

    Coïsson, Marco; Barrera, Gabriele; Celegato, Federica; Martino, Luca; Kane, Shashank N; Raghuvanshi, Saroj; Vinai, Franco; Tiberto, Paola

    2017-06-01

    Magnetic hysteresis loops areas and hyperthermia on magnetic nanoparticles have been studied with the aim of providing reliable and reproducible methods of measuring the specific absorption rate (SAR). The SAR of Fe 3 O 4 nanoparticles with two different mean sizes, and Ni 1-x Zn x Fe 2 O 4 ferrites with 0 ≤ x ≤ 0.8 has been measured with three approaches: static hysteresis loops areas, dynamic hysteresis loops areas and hyperthermia of a water solution. For dynamic loops and thermometric measurements, specific experimental setups have been developed, that operate at comparable frequencies (≈ 69kHz and ≈ 100kHz respectively) and rf magnetic field peak values (up to 100mT). The hyperthermia setup has been fully modelled to provide a direct measurement of the SAR of the magnetic nanoparticles by taking into account the heat exchange with the surrounding environment in non-adiabatic conditions and the parasitic heating of the water due to ionic currents. Dynamic hysteresis loops are shown to provide an accurate determination of the SAR except for superparamagnetic samples, where the boundary with a blocked regime could be crossed in dynamic conditions. Static hysteresis loops consistently underestimate the specific absorption rate but can be used to select the most promising samples. A means of reliably measure SAR of magnetic nanoparticles by different approaches for hyperthermia applications is presented and its validity discussed by comparing different methods. This work fits within the general subject of metrological traceability in medicine with a specific focus on magnetic hyperthermia. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editor: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Water dispersible superparamagnetic Cobalt iron oxide nanoparticles for magnetic fluid hyperthermia

    Salunkhe, Ashwini B. [Centre for advanced materials research, Department of Physics, Savitribai Phule Pune University, Pune 411007 (India); Soft matter and molecular biophysics group, Department of Applied Physics, University of Santiago de Compostela, Santiago de Compostela (Spain); Khot, Vishwajeet M. [Department of Physics and Astronomy, University College London (United Kingdom); Ruso, Juan M. [Soft matter and molecular biophysics group, Department of Applied Physics, University of Santiago de Compostela, Santiago de Compostela (Spain); Patil, S.I., E-mail: patil@physics.unipune.ac.in [Centre for advanced materials research, Department of Physics, Savitribai Phule Pune University, Pune 411007 (India)

    2016-12-01

    Superparamagnetic nanoparticles of Cobalt iron oxide (CoFe{sub 2}O{sub 4}) are synthesized chemically, and dispersed in an aqueous suspension for hyperthermia therapy application. Different parameters such as magnetic field intensity, particle concentration which regulates the competence of CoFe{sub 2}O{sub 4} nanoparticle as a heating agents in hyperthermia are investigated. Specific absorption rate (SAR) decreases with increase in the particle concentration and increases with increase in applied magnetic field intensity. Highest value of SAR is found to be 91.84 W g{sup −1} for 5 mg. mL{sup −1} concentration. Oleic acid conjugated polyethylene glycol (OA-PEG) coated CoFe{sub 2}O{sub 4} nanoparticles have shown superior cyto-compatibility over uncoated nanoparticles to L929 mice fibroblast cell lines for concentrations below 2 mg. mL{sup −1}. Present work provides the underpinning for the use of CoFe{sub 2}O{sub 4} nanoparticles as a potential heating mediator for magnetic fluid hyperthermia. - Highlights: • Superparamagnetic, water dispersible CoFe{sub 2}O{sub 4} NPs were synthesized by simple and cost effective Co precipitation route. • Effect of coating on various physical and chemical properties of CoFe{sub 2}O{sub 4} NPs were studied. • The effect of coating on induction heating as well as biocompatibility of NPs were studied.

  1. Induction heating studies of combustion synthesized MgFe2O4 nanoparticles for hyperthermia applications

    Khot, V.M.; Salunkhe, A.B.; Thorat, N.D.; Phadatare, M.R.; Pawar, S.H.

    2013-01-01

    The structural, magnetic and ac magnetically induced heating characteristics of combustion synthesized MgFe 2 O 4 nanoparticles have been investigated for application in magnetic particle hyperthermia. As prepared nanoparticles showed ferrimagnetic behavior at room temperature with magnetization of about 33.83 emu/g at ±15 kOe. The solid state MgFe 2 O 4 nanoparticles exhibited specific absorption rate (SAR) of about 297 W/g at physiological safe range of frequency and amplitude. The increase in SAR and heating temperature in ac magnetic field was thought to be due to enhancement in magnetic hysteresis loss caused by dipole–dipole interactions in combustion synthesized MgFe 2 O 4 nanoparticles. - Highlights: ► Highly crystalline pure MgFe 2 O 4 nanoparticles were synthesized by low temperature combustion. ► Effect of ac magnetic field and nanoparticles concentration on heating characteristics of MgFe 2 O 4 nanoparticles was studied. ► Combustion synthesized MgFe 2 O 4 nanoparticles show highest specific absorption rate of 297 Wg −1 . ► The reported high value of specific absorption rate is advantageous for its use in magnetic particle hyperthermia

  2. Targeted hyperthermia after selective embolization with ferromagnetic nanoparticles in a VX2 rabbit liver tumor model

    Sun HL

    2013-10-01

    Full Text Available Hongliang Sun,1 Linfeng Xu,1 Tianyuan Fan,2 Hongzhi Zhan,3 Xiaodong Wang,3 Yanfei Zhou,2 Ren-jie Yang3 1Department of Interventional Therapy, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, 2Pharmacy School of Beijing University, Beijing, 3Department of Interventional Therapy, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China Background: The purpose of this study was to observe the effect and feasibility of hyperthermia and the influence of heat on surrounding organs in a VX2 rabbit liver model exposed to an alternating magnetic field after embolization with ferromagnetic nanoparticles. Methods: Forty rabbits containing implanted hepatic VX2 carcinomas were divided into four groups, each containing ten rabbits. Fourteen days after tumor transplantation, we opened the abdomen to observe the size and shape of the tumor. A transfemoral retrograde approach was then used for hepatic arterial catheterization in groups B, C, and D to perform angiography and embolization. The next day, three rabbits in group B and all rabbits in group D were exposed to an alternating magnetic field, and the temperature was recorded simultaneously in the center of the tumor, at the edge of the tumor, and in the normal liver parenchyma. On day 28, all animals was euthanized to observe changes in the implanted liver tumor and the condition of the abdomen. A pathologic examination was also done. Results: Before surgery, there was no significant difference in tumor volume between the four groups. Three different temperature points (center of the tumor, edge of the tumor, and in the normal liver parenchyma of group B under an alternating magnetic field were 37.2°C ± 1.1°C, 36.8°C ± 1.2°C, and 36.9°C ± 2.1°C, none of which were significantly different from pretreatment values. Three points basal temperature in group D showed no significant difference (F = 1.038, P = 0.413. Seven to 26

  3. Hyperthermia: an effective strategy to induce apoptosis in cancer cells.

    Ahmed, Kanwal; Tabuchi, Yoshiaki; Kondo, Takashi

    2015-11-01

    Heat has been used as a medicinal and healing modality throughout human history. The combination of hyperthermia (HT) with radiation and anticancer agents has been used clinically and has shown positive results to a certain extent. However, the clinical results of HT treatment alone have been only partially satisfactory. Cell death following HT treatment is a function of both temperature and treatment duration. HT induces cancer cell death through apoptosis; the degree of apoptosis and the apoptotic pathway vary in different cancer cell types. HT-induced reactive oxygen species production are responsible for apoptosis in various cell types. However, the underlying mechanism of signal transduction and the genes related to this process still need to be elucidated. In this review, we summarize the molecular mechanism of apoptosis induced by HT, enhancement of heat-induced apoptosis, and the genetic network involved in HT-induced apoptosis.

  4. Radiotherapy and local hyperthermia plus androgen suppression in locally advanced prostate cancer

    Maluta, S.; Marciai, N.; Gabbani, M.; Palazzi, M.; Dall'Oglio, S.; Grandinetti, A.

    2005-01-01

    Full text: In advanced prostatic cancer, hyperthermia may be useful in order to enhance irradiation efficacy so to avoid delivering of too high dose of radiotherapy which increases acute and late sequelae. A multi-centric phase II study is warranted to give hyperthermia a level 3 evidence in prostate cancer treatment. A randomized phase III study to demonstrate efficacy of hyperthermia is not available because of the optimal results obtained by using radiotherapy combined with androgen suppression. To evaluate hyperthermia gain, LHT should be combined with radiotherapy alone in patients refusing androgen suppression or affected by hormone refractory prostate carcinoma (HRPC). Patients with HRPC have multiple possibilities of treatment improving performance status and median survival, as chemotherapy regimens, and new agents. All these treatments modalities need to be confirmed by phase III trials. Also hyperthermia may be considered among these promising approaches. (author)

  5. Local radiofrequency-induced hyperthermia using CuNi nanoparticles with therapeutically suitable Curie temperature

    Kuznetsov, Anatoly A.; Leontiev, Vladimir G.; Brukvin, Vladimir A.; Vorozhtsov, Georgy N.; Kogan, Boris Ya.; Shlyakhtin, Oleg A.; Yunin, Alexander M.; Tsybin, Oleg I.; Kuznetsov, Oleg A.

    2007-01-01

    Copper-nickel (CuNi) alloy nanoparticles with Curie temperatures (T c ) from 40 to 60 o C were synthesized by several techniques. Varying the synthesis parameters and post-treatment, as well as separations by size and T c , allow producing mediator nanoparticles for magnetic fluid hyperthermia with parametric feedback temperature control with desired parameters. In vitro and in vivo animal experiments have demonstrated the feasibility of the temperature-controlled heating of the tissue, laden with the particles, by an external alternating magnetic field

  6. Local radiofrequency-induced hyperthermia using CuNi nanoparticles with therapeutically suitable Curie temperature

    Kuznetsov, Anatoly A. [Institute of Biochemical Physics, Russian Academy of Sciences (RAS), Moscow 119991 (Russian Federation); Leontiev, Vladimir G. [Institute of Metallurgy, Russian Academy of Sciences (RAS), Moscow 119991 (Russian Federation); Brukvin, Vladimir A. [Institute of Metallurgy, Russian Academy of Sciences (RAS), Moscow 119991 (Russian Federation); Vorozhtsov, Georgy N. [NIOPIK Organic Intermediates and Dyes Institute, Moscow 103787 (Russian Federation); Kogan, Boris Ya. [NIOPIK Organic Intermediates and Dyes Institute, Moscow 103787 (Russian Federation); Shlyakhtin, Oleg A. [Institute of Chemical Physics, Russian Academy of Sciences (RAS), Kosygin St. 4, Moscow 119991 (Russian Federation); Yunin, Alexander M. [Institute of Biochemical Physics, Russian Academy of Sciences (RAS), Moscow 119991 (Russian Federation); Tsybin, Oleg I. [Institute of Metallurgy, Russian Academy of Sciences (RAS), Moscow 119991 (Russian Federation); Kuznetsov, Oleg A. [Institute of Biochemical Physics, Russian Academy of Sciences (RAS), Moscow 119991 (Russian Federation)]. E-mail: kuznetsov_oa@yahoo.com

    2007-04-15

    Copper-nickel (CuNi) alloy nanoparticles with Curie temperatures (T{sub c}) from 40 to 60{sup o}C were synthesized by several techniques. Varying the synthesis parameters and post-treatment, as well as separations by size and T{sub c}, allow producing mediator nanoparticles for magnetic fluid hyperthermia with parametric feedback temperature control with desired parameters. In vitro and in vivo animal experiments have demonstrated the feasibility of the temperature-controlled heating of the tissue, laden with the particles, by an external alternating magnetic field.

  7. Surface functionalized biocompatible magnetic nanospheres for cancer hyperthermia.

    Liu, X.; Novosad, V.; Rozhkova, E. A.; Chen, H.; Yefremenko, V.; Pearson, J.; Torno, M.; Bader, S. D.; Rosengart, A. J.; Univ. Chicago Pritzker School of Medicine

    2007-06-01

    We report a simplified single emulsion (oil-in-water) solvent evaporation protocol to synthesize surface functionalized biocompatible magnetic nanospheres by using highly concentrated hydrophobic magnetite (gel) and a mixture of poly(D,L lactide-co-glycolide) (PLGA) and poly(lactic acid-block-polyethylene glycol-maleimide) (PLA-PEG-maleimide) (10:1 by mass) polymers. The as-synthesized particles are approximately spherical with an average diameter of 360-370 nm with polydispersity index of 0.12-0.18, are surface-functionalized with maleimide groups, and have saturation magnetization values of 25-40 emu/g. The efficiency of the heating induced by 400-kHz oscillating magnetic fields is compared for two samples with different magnetite loadings. Results show that these nanospheres have the potential to provide an efficient cancer-targeted hyperthermia.

  8. Modelling mass and heat transfer in nano-based cancer hyperthermia.

    Nabil, M; Decuzzi, P; Zunino, P

    2015-10-01

    We derive a sophisticated mathematical model for coupled heat and mass transport in the tumour microenvironment and we apply it to study nanoparticle delivery and hyperthermic treatment of cancer. The model has the unique ability of combining the following features: (i) realistic vasculature; (ii) coupled capillary and interstitial flow; (iii) coupled capillary and interstitial mass transfer applied to nanoparticles; and (iv) coupled capillary and interstitial heat transfer, which are the fundamental mechanisms governing nano-based hyperthermic treatment. This is an improvement with respect to previous modelling approaches, where the effect of blood perfusion on heat transfer is modelled in a spatially averaged form. We analyse the time evolution and the spatial distribution of particles and temperature in a tumour mass treated with superparamagnetic nanoparticles excited by an alternating magnetic field. By means of numerical experiments, we synthesize scaling laws that illustrate how nano-based hyperthermia depends on tumour size and vascularity. In particular, we identify two distinct mechanisms that regulate the distribution of particle and temperature, which are characterized by perfusion and diffusion, respectively.

  9. Hyperthermia treatment of tumors by mesenchymal stem cell-delivered superparamagnetic iron oxide nanoparticles

    Kalber TL

    2016-05-01

    Full Text Available Tammy L Kalber,1,2,* Katherine L Ordidge,1,2,* Paul Southern,3 Michael R Loebinger,1 Panagiotis G Kyrtatos,2,3 Quentin A Pankhurst,3,* Mark F Lythgoe,2,* Sam M Janes1,* 1Lungs for Living Research Centre, UCL Respiratory, University College London, 2UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, 3Healthcare Biomagnetics Laboratory, University College London, London, UK *These authors contributed equally to this work Abstract: Magnetic hyperthermia – a potential cancer treatment in which superparamagnetic iron oxide nanoparticles (SPIONs are made to resonantly respond to an alternating magnetic field (AMF and thereby produce heat – is of significant current interest. We have previously shown that mesenchymal stem cells (MSCs can be labeled with SPIONs with no effect on cell proliferation or survival and that within an hour of systemic administration, they migrate to and integrate into tumors in vivo. Here, we report on some longer term (up to 3 weeks post-integration characteristics of magnetically labeled human MSCs in an immunocompromized mouse model. We initially assessed how the size and coating of SPIONs dictated the loading capacity and cellular heating of MSCs. Ferucarbotran® was the best of those tested, having the best like-for-like heating capability and being the only one to retain that capability after cell internalization. A mouse model was created by subcutaneous flank injection of a combination of 0.5 million Ferucarbotran-loaded MSCs and 1.0 million OVCAR-3 ovarian tumor cells. After 2 weeks, the tumors reached ~100 µL in volume and then entered a rapid growth phase over the third week to reach ~300 µL. In the control mice that received no AMF treatment, magnetic resonance imaging (MRI data showed that the labeled MSCs were both incorporated into and retained within the tumors over the entire 3-week period. In the AMF-treated mice, heat increases of ~4°C were observed

  10. Hyperthermia for the Treatment of Locally Advanced Cervix Cancer

    M. Franckena (Martine)

    2010-01-01

    textabstract(English): There is a strong biological rationale for the use of hyperthermia as an oncological treatment modality. Fifteen randomized trials have shown significant improvement in clinical outcome when hyperthermia was added to radiotherapy, chemotherapy or both. At temperatures ≥ 40

  11. Reirradiation + hyperthermia for recurrent breast cancer en cuirasse

    Oldenborg, Sabine; Rasch, Coen R.N.; Os, Rob van; Kusumanto, Yoka H.; Voerde Sive Voerding, Paul J. zum; Crezee, Hans; Tienhoven, Geertjan van [University of Amsterdam (AMC), Department of Radiation Oncology, Z1-215, Academic Medical Center, Amsterdam (Netherlands); Oei, Bing S.; Venselaar, Jack L. [Institute Verbeeten (BVI), Department of Radiation Oncology, Tilburg (Netherlands); Heymans, Martijn W. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands)

    2018-03-15

    Patients with irresectable locoregional recurrent breast cancer en cuirasse (BCEC) do not have effective curative treatment options. Hyperthermia, the elevation of tumor temperature to 40-45 C, is a well-established radio- and chemotherapy sensitizer. A total of 196 patients were treated with reirradiation and hyperthermia (reRT+HT) at two Dutch institutes from 1982-2005. The palliative effect was evaluated in terms of clinical outcome and toxicity. All patients received previous irradiation to a median dose of 50 Gy. In all, 75% of patients received 1-6 treatment modalities for previous tumor recurrences. ReRT consisted of 8 x 4 Gy given twice a week or 12 x 3 Gy given four times a week. Superficial hyperthermia was added once or twice a week. Tumor area comprised ≥1/2 of the ipsilateral chest wall. Overall clinical response rate was 72% (complete response [CR] 30%, partial response [PR] 42%, stable disease [SD] 22%, progressive disease [PD] 6%). The local progression-free rate at 1 year was 24%. Median survival was 6.9 months. Forty-three percent of our patients with CR, PR, SD after treatment remained infield progression-free until death or last follow-up. Acute ≥grade 3 toxicity occurred in 33% of patients, while late ≥grade 3 toxicity was recorded in 14% of patients. Tumor ulceration prior to treatment had a negative impact on both clinical outcome and toxicity. ReRT+HT provides sustainable palliative tumor control, despite refractory, extensive tumor growth. Compared to currently available systemic treatment options, reRT+HT is more effective with less toxicity. (orig.) [German] Fuer Patienten mit inoperablen lokoregionalen Rueckfaellen von Brustkrebs in Form eines Cancer en cuirasse (BCEC) gibt es keine effektiven kurativen Behandlungsoptionen. Die Hyperthermie, bei der die Tumortemperatur auf 40-45 C erhoeht wird, ist eine etablierte Methode zur Radio- und Chemotherapiesensibilisierung. Insgesamt 161 Patientinnen wurden in zwei niederlaendischen

  12. Hyperthermia of locally advanced or recurrent gynecological cancer. The effect of combination with irradiation or chemotherapy

    Terashima, Hiromi; Imada, Hajime; Egashira, Kanji; Nakata, Hajime; Kunugita, Naoki; Matsuura, Yuusuke; Kashimura, Masamichi

    1995-01-01

    Between May 1986 and April 1994, 15 patients with advanced or recurrent gynecological cancer were treated with combined therapy of hyperthermia and irradiation or chemotherapy at UOEH Hospital. Initial cases were treated by hyperthermia combined with irradiation in 4 and with chemotherapy in 2. Recurrent 9 cases were treated by hyperthermia combined with chemotherapy or by hyperthermia alone. Radiotherapy was given in a conventional way 5 fractions per week and hyperthermia was performed using RF capacitive heating equipment, Thermotron RF-8, once or twice a week. Intratumoral temperature was measured by thermocouple inserted into the tumor and kept at 42-44degC for 30-40 minutes. Complete response (CR) and partial response (PR), defined as 50% or more regression, was obtained in 8/15 (53%). Response rates (CR+PR/all cases) were good in initially treated cases (5/6, 83%), irradiated cases (7/8, 88%) and cases hearted over 42degC (7/9, 78%). Combined therapy of hyperthermia and radiotherapy seemed to be useful for controlling advanced gynecological cancers. (author)

  13. Curcumin and 5-Fluorouracil-loaded, folate- and transferrin-decorated polymeric magnetic nanoformulation: a synergistic cancer therapeutic approach, accelerated by magnetic hyperthermia

    Balasubramanian S

    2014-01-01

    Full Text Available Sivakumar Balasubramanian,1 Aswathy Ravindran Girija,1 Yutaka Nagaoka,1 Seiki Iwai,1 Masashi Suzuki,1 Venugopal Kizhikkilot,2 Yasuhiko Yoshida,1 Toru Maekawa,1 Sakthikumar Dasappan Nair1 1Bio Nano Electronics Research Center, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Japan; 2Department of Respiratory Medicine, Sooriya Hospital, Chennai, India Abstract: The efficient targeting and therapeutic efficacy of a combination of drugs (curcumin and 5-Fluorouracil [5FU] and magnetic nanoparticles encapsulated poly(D,L-lactic-co-glycolic acid nanoparticles, functionalized with two cancer-specific ligands are discussed in our work. This multifunctional, highly specific nanoconjugate resulted in the superior uptake of nanoparticles by cancer cells. Upon magnetic hyperthermia, we could harness the advantages of incorporating magnetic nanoparticles that synergistically acted with the drugs to destroy cancer cells within a very short period of time. The remarkable multimodal efficacy attained by this therapeutic nanoformulation offers the potential for targeting, imaging, and treatment of cancer within a short period of time (120 minutes by initiating early and late apoptosis. Keywords: nanotechnology, curcumin, 5FU, folate, transferrin, PLGA nanoparticle, magnetic hyperthermia

  14. A/C magnetic hyperthermia of melanoma mediated by iron(0)/iron oxide core/shell magnetic nanoparticles: a mouse study

    Balivada, Sivasai; Koper, Olga B; Tamura, Masaaki; Chikan, Viktor; Bossmann, Stefan H; Troyer, Deryl L; Rachakatla, Raja Shekar; Wang, Hongwang; Samarakoon, Thilani N; Dani, Raj Kumar; Pyle, Marla; Kroh, Franklin O; Walker, Brandon; Leaym, Xiaoxuan

    2010-01-01

    There is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy. The influence of bimagnetic nanoparticles (MNPs) combined with short external alternating magnetic field (AMF) exposure on the growth of subcutaneous mouse melanomas (B16-F10) was evaluated. Bimagnetic Fe/Fe 3 O 4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin) units were attached to the dopamine-oligoethylene glycol ligands. The magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe 3 O 4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. We also observed a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure 24 hrs after the MNPs injection. These results indicate that intratumoral administration of surface modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, we have found that after intravenous administration of micromolar concentrations, these MNPs are capable of causing an anti-tumor effect in a mouse melanoma model after only a short AMF exposure time. This is a clear improvement to state of the art

  15. RGD-conjugated iron oxide magnetic nanoparticles for magnetic resonance imaging contrast enhancement and hyperthermia.

    Zheng, S W; Huang, M; Hong, R Y; Deng, S M; Cheng, L F; Gao, B; Badami, D

    2014-03-01

    The purpose of this study was to develop a specific targeting magnetic nanoparticle probe for magnetic resonance imaging and therapy in the form of local hyperthermia. Carboxymethyl dextran-coated ultrasmall superparamagnetic iron oxide nanoparticles with carboxyl groups were coupled to cyclic arginine-glycine-aspartic peptides for integrin α(v)β₃ targeting. The particle size, magnetic properties, heating effect, and stability of the arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide were measured. The arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide demonstrates excellent stability and fast magneto-temperature response. Magnetic resonance imaging signal intensity of Bcap37 cells incubated with arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide was significantly decreased compared with that incubated with plain ultrasmall superparamagnetic iron oxide. The preferential uptake of arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide by target cells was further confirmed by Prussian blue staining and confocal laser scanning microscopy.

  16. Optimal size for heating efficiency of superparamagnetic dextran-coated magnetite nanoparticles for application in magnetic fluid hyperthermia

    Shaterabadi, Zhila; Nabiyouni, Gholamreza; Soleymani, Meysam

    2018-06-01

    Dextran-coated magnetite (Fe3O4) nanoparticles with average particle sizes of 4 and 19 nm were synthesized through in situ and semi-two-step co-precipitation methods, respectively. The experimental results confirm the formation of pure phase of magnetite as well as the presence of dextran layer on the surface of modified magnetite nanoparticles. The results also reveal that both samples have the superparamagnetic behavior. Furthermore, calorimetric measurements show that the dextran-coated Fe3O4 nanoparticles with an average size of 4 nm cannot produce any appreciable heat under a biologically safe alternating magnetic field used in hyperthermia therapy; whereas, the larger ones (average size of 19 nm) are able to increase the temperature of their surrounding medium up to above therapeutic range. In addition, measured specific absorption rate (SAR) values confirm that magnetite nanoparticles with an average size of 19 nm are very excellent candidates for application in magnetic hyperthermia therapy.

  17. Local hyperthermia and artificial hyperglycemia in combined treatment of patients with rectum cancer

    Bezmen, V.A.; Illarionov, A.A.; Novokhrost, V.I.; Shilov, N.I.; Ospishchev, A.A.; Kejs, G.D.

    1990-01-01

    To study prospects of application of local hyperthermia, artificial hyperglycemia and radiotherapy in a preoperative period, 31 patients with rectum cancer were studied. The treatment included 3-hour artificial hyperglycemia first, then local SHF hyperthermia and telegamma irradiation using large-fractioned doses (ROD is 5 Gy, COD is 20 Gy). No serious side-effects were observed during the preoperative treatment period. The immediate and early results of combined treatment promise to improve the effectiveness of treatment of patients with rectum cancer. 3 refs

  18. Numerical analysis of temperature field improvement with nanoparticles designed to achieve critical power dissipation in magnetic hyperthermia

    Tang, Yundong; Flesch, Rodolfo C. C.; Jin, Tao

    2017-07-01

    Magnetic nanoparticle (MNP) hyperthermia is a promising emerging therapy for cancer treatment that is minimally invasive and has been successfully used to treat different types of tumors. The power dissipation of MNPs, which is one of the most important factors during a hyperthermia treatment, is determined by the properties of MNPs and characteristics of the magnetic field. This paper proposes a method based on the finite element analysis for determining the value of the power dissipation of particles (PDP) that can maximize the average temperature of the tumor during treatment and at the same time guarantee that the maximum temperature is within the therapeutic range. The application of the critical PDP value can improve the effectiveness of the treatment since it increases the average temperature in the tumor region while limiting the damage to the healthy tissue that surrounds it. After the critical PDP is determined for a specific model, it is shown how the properties of the MNPs can be chosen to achieve the desired PDP value. The transient behavior of the temperature distribution for two different models considering blood vessels is analyzed as a case study, showing that the presence of a blood vessel inside the tumor region can significantly decrease the uniformity of the temperature field and also increase the treatment duration given its cooling effects. To present a solution that does not depend upon a good model of the tumor region, an alternative method that uses MNPs with low Curie temperature is proposed, given the temperature self-regulating properties of such MNPs. The results demonstrate that the uniformity of the temperature field can be significantly increased by combining the optimization procedure proposed in this paper with the use of low-Curie-temperature MNPs.

  19. Evaluation of magnetic fluid hyperthermia (MFH) combined with external radiation in an orthotopic rat model of prostate cancer

    Johannsen, M.; Thiesen, B.; Taymoorian, K.; Gneveckow, U.; Waldoefner, N.; Koch, M.; Scholz, R.; Lein, M.; Jung, K.; Loening, S.A.; Jordan, A.

    2005-01-01

    Full text: Magnetic fluid hyperthermia (MFH) is a new concept of cancer treatment based on AC magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. Preliminary studies of MFH using nanoscaled aminosilan-coated magnetites have demonstrated the feasibility of minimally invasive MFH in the Dunning tumor model. Here we evaluated the effect of two sequential MFH treatments, combined with external radiation, in an orthotopic Dunning R3327-MatLyLu prostate cancer model. MFH led to a significant growth inhibition in this orthotopic model of the aggressive MatLyLu tumor variant. Furthermore, combined MFH and radiation with 20 Gy equally effective in inhibiting tumor growth as radiation with 60 Gy, suggesting a significant synergistic effect. Intratumoral deposition of magnetic fluids was found to be stable, allowing for serial MFH treatments without repeated injection. The optimal treatment schedules of this combination regarding temperatures, sequencing and fractionation need to be defined in further experimental studies. (author)

  20. Specific absorption rate determination of magnetic nanoparticles through hyperthermia measurements in non-adiabatic conditions

    Coïsson, M. [INRIM, strada delle Cacce 91, 10135 Torino (Italy); Barrera, G. [INRIM, strada delle Cacce 91, 10135 Torino (Italy); University of Torino, Chemistry Department, via P. Giuria 7, 10125 Torino (Italy); Celegato, F.; Martino, L.; Vinai, F. [INRIM, strada delle Cacce 91, 10135 Torino (Italy); Martino, P. [Politronica srl, via Livorno 60, 10144 Torino (Italy); Ferraro, G. [Center for Space Human Robotics, Istituto Italiano di Tecnologia - IIT, corso Trento 21, 10129 Torino (Italy); Tiberto, P. [INRIM, strada delle Cacce 91, 10135 Torino (Italy)

    2016-10-01

    An experimental setup for magnetic hyperthermia operating in non-adiabatic conditions is described. A thermodynamic model that takes into account the heat exchanged by the sample with the surrounding environment is developed. A suitable calibration procedure is proposed that allows the experimental validation of the model. Specific absorption rate can then be accurately determined just from the measurement of the sample temperature at the equilibrium steady state. The setup and the measurement procedure represent a simplification with respect to other systems requiring calorimeters or crucial corrections for heat flow. Two families of magnetic nanoparticles, one superparamagnetic and one characterised by larger sizes and static hysteresis, have been characterised as a function of field intensity, and specific absorption rate and intrinsic loss power have been obtained. - Highlights: • Development and thermodynamic modelling of a hyperthermia setup operating in non-adiabatic conditions. • Calibration of the experimental setup and validation of the model. • Accurate measurement of specific absorption rate and intrinsic loss power in non-adiabatic conditions.

  1. Magnetic hyperthermia properties of iron oxide nanoparticles: The effect of concentration

    Ebrahimisadr, Saeid; Aslibeiki, Bagher; Asadi, Reza

    2018-06-01

    We investigated the effect of concentration on magnetic hyperthermia properties of Fe3O4 nanoparticles (NPs). The NPs were synthesized by co-precipitation method at 80 °C. Scanning electron microscope image showed that the mean diameter of NPs is about 18 nm. The XRD pattern indicated that the sample is pure Fe3O4 with spinel structure and the FT-IR spectroscopy confirmed formation of metal-oxygen bonds in the octahedral and tetrahedral spinel sub-lattice which further confirmed crystalline structure of the sample. The hyperthermia property of Fe3O4 NPs was investigated via an induction heater generating alternating magnetic field with frequency of 92 kHz. The temperature rise (ΔT) of suspension in the AC magnetic field was studied on different concentrations of NPs and the specific absorption rate (SAR) was obtained from Box-Lucas equation and linear fitting of ΔT-time curve. The results showed that the ΔT sharply increases with increasing the NPs concentration while the SAR remains almost constant.

  2. Magnetic nanoparticles with high specific absorption rate of electromagnetic energy at low field strength for hyperthermia therapy

    Shubitidze, Fridon; Kekalo, Katsiaryna; Stigliano, Robert; Baker, Ian

    2015-03-01

    Magnetic nanoparticles (MNPs), referred to as the Dartmouth MNPs, which exhibit high specific absorption rate at low applied field strength have been developed for hyperthermia therapy applications. The MNPs consist of small (2-5 nm) single crystals of gamma-Fe2O3 with saccharide chains implanted in their crystalline structure, forming 20-40 nm flower-like aggregates with a hydrodynamic diameter of 110-120 nm. The MNPs form stable (>12 months) colloidal solutions in water and exhibit no hysteresis under an applied quasistatic magnetic field, and produce a significant amount of heat at field strengths as low as 100 Oe at 99-164 kHz. The MNP heating mechanisms under an alternating magnetic field (AMF) are discussed and analyzed quantitatively based on (a) the calculated multi-scale MNP interactions obtained using a three dimensional numerical model called the method of auxiliary sources, (b) measured MNP frequency spectra, and (c) quantified MNP friction losses based on magneto-viscous theory. The frequency responses and hysteresis curves of the Dartmouth MNPs are measured and compared to the modeled data. The specific absorption rate of the particles is measured at various AMF strengths and frequencies, and compared to commercially available MNPs. The comparisons demonstrate the superior heating properties of the Dartmouth MNPs at low field strengths (therapy to deeper tumors that were previously non-viable targets, potentially enabling the treatment of some of the most difficult cancers, such as pancreatic and rectal cancers, without damaging normal tissue.

  3. Improvement of drug delivery by hyperthermia treatment using magnetic cubic cobalt ferrite nanoparticles

    Dey, Chaitali, E-mail: chaitalidey29@gmail.com [Centre for Research in Nanoscience & Nanotechnology, Block-JD-2, Sector-III, Salt Lake, Kolkata 700106 (India); Baishya, Kaushik [S.N. Bose National Centre for Basic Sciences, Block-JD, Sector-III, Salt Lake, Kolkata 700106 (India); Ghosh, Arup [S.N. Bose National Centre for Basic Sciences, Block-JD, Sector-III, Salt Lake, Kolkata 700106 (India); Department of Physics, Indian Institute of Science Education and Research (IISER) Pune, Dr. Homi Bhabha Road, Pashan, Pune 411008 (India); Goswami, Madhuri Mandal, E-mail: madhuri@bose.res.in [S.N. Bose National Centre for Basic Sciences, Block-JD, Sector-III, Salt Lake, Kolkata 700106 (India); Ghosh, Ajay [Dept. of Applied Optics and Photonics, University of Calcutta, Block-JD-2, Sector-III, Salt Lake, Kolkata 700106 (India); Mandal, Kalyan [S.N. Bose National Centre for Basic Sciences, Block-JD, Sector-III, Salt Lake, Kolkata 700106 (India)

    2017-04-01

    In this study, we report a novel synthesis method, characterization and application of a new class of ferromagnetic cubic cobalt ferrite magnetic nanoparticles (MNPs) for hyperthermia therapy and temperature triggered drug release. The MNPs are characterized by XRD, TEM, FESEM, AC magnetic hysteresis and VSM. These MNPs were coated with folic acid and loaded with an anticancer drug. The drug release studies were done at two different temperatures (37 °C and 44 °C) with progress of time. It was found that higher release of drug took place at elevated temperature (44 °C). We have developed a temperature sensitive drug delivery system which releases the heat sensitive drug selectively as the particles are heated up under AC magnetic field and controlled release is possible by changing the external AC magnetic field.

  4. Magnetic hyperthermia heating of cobalt ferrite nanoparticles prepared by low temperature ferrous sulfate based method

    Tejabhiram Yadavalli

    2016-05-01

    Full Text Available A facile low temperature co-precipitation method for the synthesis of crystalline cobalt ferrite nanostructures using ferrous sulfate salt as the precursor has been discussed. The prepared samples were compared with nanoparticles prepared by conventional co-precipitation and hydrothermal methods using ferric nitrate as the precursor. X-ray diffraction studies confirmed the formation of cubic spinel cobalt ferrites when dried at 110 °C as opposed to conventional methods which required higher temperatures/pressure for the formation of the same. Field emission scanning electron microscope studies of these powders revealed the formation of nearly spherical nanostructures in the size range of 20-30 nm which were comparable to those prepared by conventional methods. Magnetic measurements confirmed the ferromagnetic nature of the cobalt ferrites with low magnetic remanance. Further magnetic hyperthermia studies of nanostructures prepared by low temperature method showed a rise in temperature to 50 °C in 600 s.

  5. Rib fractures after reirradiation plus hyperthermia for recurrent breast cancer: Predictive factors

    Oldenborg, Sabine; Valk, Christel; van Os, Rob; Oei, Bing; Venselaar, Jack; Vörding, Paul Zum Vörde Sive; van Randen, Adriënne; Crezee, Hans; van Tienhoven, Geertjan; Rasch, Coen

    2016-01-01

    Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors

  6. Measurement of the distribution of anisotropy constants in magnetic nanoparticles for hyperthermia applications

    McGhie, A. A.; Marquina, C.; O'Grady, K.; Vallejo-Fernandez, G.

    2017-11-01

    In this work, we have applied theoretical calculations to new experimental measurements of the effect of the anisotropy distribution in magnetite nanoparticles, which in turn controls hysteresis heating for hyperthermia applications. Good agreement between theory and experiment is reported where the theoretical calculation is based upon the detailed measurement of the particle elongation generally observed in the nanoparticles. The elongation has been measured from studies via transmission electron microscopy. We find that particle elongation is responsible for the anisotropy dispersion, which can be obtained by analysis and fitting to a measurement of the temperature decay of remanence. A median value of the anisotropy constant of 1.5  ×  105 erg/cc was obtained. A very wide distribution of anisotropy constants is present with a Gaussian standard deviation of 1.5  ×  105 erg/cc. From our measurements, deviations in the value of the saturation magnetisation from particle to particle are most likely the main factor giving rise to this large distribution, with 33% arising from the error in the measured elongation. The lower limit to the anisotropy constant of the nanoparticles is determined by the magnetocrystalline anisotropy of the material, 1.1  ×  105 erg/cc for magnetite, which was studied in this work.

  7. Exchange-coupled Fe3O4/CoFe2O4 nanoparticles for advanced magnetic hyperthermia

    Glassell, M.; Robles, J.; Das, R.; Phan, M. H.; Srikanth, H.

    Iron oxide nanoparticles especially Fe3O4, γ-Fe2O3 have been extensively studied for magnetic hyperthermia because of their tunable magnetic properties and stable suspension in superparamagnetic regime. However, their relatively low heating capacity hindered practical application. Recently, a large improvement in heating efficiency has been reported in exchange-coupled nanoparticles with exchange coupling between soft and hard magnetic phases. Here, we systematically studied the effect of core and shell size on the heating efficiency of the Fe3O4/CoFe2O4 core/shell nanoparticles. The nanoparticles were synthesized using thermal decomposition of organometallic precursors. Transmission electron microscopy (TEM) showed formation of spherical shaped Fe3O4 and Fe3O-/CoFe2O4 nanoparticles. Magnetic measurements showed high magnetization (≅70 emu/g) and superparamagnetic behavior for the nanoparticles at room temperature. Magnetic hyperthermia results showed a large increase in specific absorption rate (SAR) for 8nm Fe3O4/CoFe2O4 compared to Fe3O4 nanoparticles of the same size. The heating efficiency of the Fe3O4/CoFe2O4 with 1 nm CoFe2O4 (shell) increased from 207 to 220 W/g (for 800 Oe) with increase in core size from 6 to 8 nm. The heating efficiency of the Fe3O4/CoFe2O4 with 2 nm CoFe2O4 (shell) and core size of 8 nm increased from 220 to 460 W/g (for 800 Oe). These exchange-coupled Fe3O4/CoFe2O4 core/shell nanoparticles can be a good candidate for advanced hyperthermia application.

  8. Magnetic hyperthermia studies on water-soluble polyacrylic acid-coated cobalt ferrite nanoparticles

    Krishna Surendra, M. [Indian Institute of Technology Madras, Department of Physics, Nano Functional Materials Technology Centre, Materials Research Centre (India); Annapoorani, S. [Anna University of Technology, Department of Nanotechnology (India); Ansar, Ereath Beeran; Harikrishna Varma, P. R. [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Bioceramics Laboratory (India); Ramachandra Rao, M. S., E-mail: msrrao@iitm.ac.in [Indian Institute of Technology Madras, Department of Physics, Nano Functional Materials Technology Centre, Materials Research Centre (India)

    2014-12-15

    We report on synthesis and hyperthermia studies in the water-soluble ferrofluid made of polyacrylic acid-coated cobalt ferrite (CoFe{sub 2}O{sub 4}) nanoparticles with different particle sizes. Magnetic nanoparticles were synthesized using co-precipitation method and particle size was varied as 6, 10, and 14 nm by varying the precursor to surfactant concentration. PAA surfactant bonding and surfactant thickness were studied by FTIR and thermogravimetric analysis. At room temperature, nanoparticles show superparamagnetism and saturation magnetization was found to vary from 33 to 44 emu/g with increase in the particle size from 6 to 14 nm, and this increase was attributed to the presence of a magnetic inert layer of 4 Å thick. Effect of particle size, concentration, and alternating magnetic field strength at 275 kHz on specific absorption rate were studied by preparing ferrofluids in deionized water at different concentrations. Ferrofluids at a concentration of 1.25 g/L, with 10 min of AMF exposure of strength ∼15.7 kA/m show stable temperatures ∼48, 58, and 68 °C with increase in the particle sizes 6, 10, and 14 nm. A maximum specific absorption rate of 251 W/g for ferrofluid with a particle size of 10 nm at 1.25 g/L, 15.7 kA/m, and 275 kHz was observed. Viability of L929 fibroblasts is measured by MTT assay cytotoxicity studies using the polyacrylic acid-coated CoFe{sub 2}O{sub 4} nanoparticles.

  9. Dynamical Origin of Highly Efficient Energy Dissipation in Soft Magnetic Nanoparticles for Magnetic Hyperthermia Applications

    Kim, Min-Kwan; Sim, Jaegun; Lee, Jae-Hyeok; Kim, Miyoung; Kim, Sang-Koog

    2018-05-01

    We explore robust magnetization-dynamic behaviors in soft magnetic nanoparticles in single-domain states and find their related high-efficiency energy-dissipation mechanism using finite-element micromagnetic simulations. We also make analytical derivations that provide deeper physical insights into the magnetization dynamics associated with Gilbert damping parameters under applications of time-varying rotating magnetic fields of different strengths and frequencies and static magnetic fields. Furthermore, we find that the mass-specific energy-dissipation rate at resonance in the steady-state regime changes remarkably with the strength of rotating fields and static fields for given damping constants. The associated magnetization dynamics are well interpreted with the help of the numerical calculation of analytically derived explicit forms. The high-efficiency energy-loss power can be obtained using soft magnetic nanoparticles in the single-domain state by tuning the frequency of rotating fields to the resonance frequency; what is more, it is controllable via the rotating and static field strengths for a given intrinsic damping constant. We provide a better and more efficient means of achieving specific loss power that can be implemented in magnetic hyperthermia applications.

  10. Shielding of Sensitive Electronic Devices in Magnetic Nanoparticle Hyperthermia Using Arrays of Coils

    Spirou, S V; Tsialios, P; Loudos, G

    2015-01-01

    In Magnetic Nanoparticle Hyperthermia (MNH) an externally applied electromagnetic field transfers energy to the magnetic nanoparticles in the body, which in turn convert this energy into heat, thus locally heating the tissue they are located in. This external electromagnetic field is sufficiently strong so as to cause interference and affect sensitive electronic equipment. Standard shielding of magnetic fields involves Faraday cages or coating with high-permeability shielding alloys; however, these techniques cannot be used with optically sensitive devices, such as those employed in Optical Coherence Tomography or radionuclide imaging. In this work we present a method to achieve magnetic shielding using an array of coils. The magnetic field generated by a single coil was calculated using the COMSOL physics simulation toolkit. Software was written in C/C++ to import the single-coil data, and then calculate the positions, number of turns and currents in the shielding coils in order to minimize the magnetic field strength at the desired location. Simulations and calculations have shown that just two shielding coils can reduce the magnetic field by 2-3 orders of magnitude. (paper)

  11. Shielding of Sensitive Electronic Devices in Magnetic Nanoparticle Hyperthermia Using Arrays of Coils

    Spirou, S. V.; Tsialios, P.; Loudos, G.

    2015-09-01

    In Magnetic Nanoparticle Hyperthermia (MNH) an externally applied electromagnetic field transfers energy to the magnetic nanoparticles in the body, which in turn convert this energy into heat, thus locally heating the tissue they are located in. This external electromagnetic field is sufficiently strong so as to cause interference and affect sensitive electronic equipment. Standard shielding of magnetic fields involves Faraday cages or coating with high-permeability shielding alloys; however, these techniques cannot be used with optically sensitive devices, such as those employed in Optical Coherence Tomography or radionuclide imaging. In this work we present a method to achieve magnetic shielding using an array of coils. The magnetic field generated by a single coil was calculated using the COMSOL physics simulation toolkit. Software was written in C/C++ to import the single-coil data, and then calculate the positions, number of turns and currents in the shielding coils in order to minimize the magnetic field strength at the desired location. Simulations and calculations have shown that just two shielding coils can reduce the magnetic field by 2-3 orders of magnitude.

  12. Combined transperineal radiofrequency (RF) interstitial hyperthermia and brachytherapy for localized prostate cancer (PC)

    Urakami, Shinji; Gonda, Nobuko; Kikuno, Nobuyuki

    2001-01-01

    Hyperthermia has been used effectively as a radiation sensitizer. Interstitial hyperthermoradiotherapy has been therefore utilized as a minimal invasive therapy in attempts to improve local tumor control for various cancers, but not for urological cancer. The purpose of this study was to investigate the safety and feasibility of transperineal hyperthermoradiotherapy for localized PC. Based on our basic study of hyperthermoradiotherapy, we devised the procedure of combined transperineal RF interstitial hyperthermia and brachytherapy for localized prostate cancer. Two patients with localized PC underwent transperineal RF interstitial hyperthermia combined with brachytherapy operation the 192-Ir remote after-loading system (RALS). Under transrectal ultrasound guidance, a total number of 12-18 stainless steel needles for 192-Ir RALS were implanted into the prostatic gland and seminal vesicles (SV) in an optimized pattern. Eight of the needles were used as electrodes for hyperthermia, and were electrically insultated using the vinyl catheter along the length of the subdermal fatty tissue to protect from overheating. Three other needles were utilized for continuous temperature mapping in the prostate. Rectal temperature was also monitored. Total radiation doses of 70 Gy to the prostate and SV were planned as a combination of brachytherapy (24 Gy/4 fraction) and external irradiation using a four-field box technique (46 Gy/23 fraction). Hyperthermic treatment (goal of 42 to 43 deg C for 60 minutes) was performed twice following the 1st and 4th brachytherapy at an interval of more than 48 hours for the recovery of cancer cells from thermotolerance. Both patients reached the treatment goal of all intraprostatic temperatures >43.0 deg C, which was considered favorable for hyperthermia, and the rectal temperatures of both patients remained <38 deg C during hyperthermia. In serial PSA measurements of both patients, serum PSA was less than 1.0 ng/ml within 3 months and has since

  13. A/C magnetic hyperthermia of melanoma mediated by iron(0/iron oxide core/shell magnetic nanoparticles: a mouse study

    Koper Olga B

    2010-03-01

    Full Text Available Abstract Background There is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy. Methods The influence of bimagnetic nanoparticles (MNPs combined with short external alternating magnetic field (AMF exposure on the growth of subcutaneous mouse melanomas (B16-F10 was evaluated. Bimagnetic Fe/Fe3O4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin units were attached to the dopamine-oligoethylene glycol ligands. Results The magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe3O4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. We also observed a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure 24 hrs after the MNPs injection. Conclusions These results indicate that intratumoral administration of surface modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, we have found that after intravenous administration of micromolar concentrations, these MNPs are capable of causing an anti-tumor effect in a mouse melanoma model after only a short AMF exposure time. This is a clear improvement to state of the art.

  14. Re-irradiation and hyperthermia after surgery for recurrent breast cancer

    Linthorst, Marianne; Geel, Albert N. van; Baaijens, Margreet; Ameziane, Ali; Ghidey, Wendim; Rhoon, Gerard C. van; Zee, Jacoba van der

    2013-01-01

    Purpose: Evaluation of efficacy and side effects of combined re-irradiation and hyperthermia electively or for subclinical disease in the management of locoregional recurrent breast cancer. Methods and materials: Records of 198 patients with recurrent breast cancer treated with re-irradiation and hyperthermia from 1993 to 2010 were reviewed. Prior treatments included surgery (100%), radiotherapy (100%), chemotherapy (42%), and hormonal therapy (57%). Ninety-one patients were treated for microscopic residual disease following resection or systemic therapy and 107 patients were treated electively for areas at high risk for local recurrences. All patients were re-irradiated to 28–36 Gy (median 32) and treated with 3–8 hyperthermia treatments (mean 4.36). Forty percent of the patients received concurrent hormonal therapy. Patient and tumor characteristics predictive for actuarial local control (LC) and toxicity were studied in univariate and multivariate analysis. Results: The median follow-up was 42 months. Three and 5 year LC-rates were 83% and 78%. Mean of T90 (tenth percentile of temperature distribution), maximum and average temperatures were 39.8 °C, 43.6 °C, and 41.2 °C, respectively. Mean of the cumulative equivalent minutes (CEM43) at T90 was 4.58 min. Number of previous chemotherapy and surgical procedures were most predictive for LC. Cumulative incidence of grade 3 and 4 late toxicity at 5 years was 11.9%. The number of thermometry sensors and depth of treatment volume were associated with acute hyperthermia toxicity. Conclusions: The combination of re-irradiation and hyperthermia results in a high LC-rate with acceptable toxicity

  15. A system for the treatment of cancer by magnetically mediated arterial embolisation hyperthermia

    Jones, S.; Moroz, P.

    2002-01-01

    Full text: Sirtex Medical Limited is developing new technology to treat cancer by induced hyperthermia. A wealth of scientific data from laboratory and animal experimentation has shown that if the temperature of cancerous tissue is maintained for some time above about 42 deg C then that cancer will be destroyed. In current clinical practice, hyperthermia therapy is mostly used as an adjunct to radiotherapy in the treatment of superficial and other easily accessible tumour sites. Restrictions to the wider application of hyperthermia to the treatment of tumours located at deep body sites are technological in nature. There are presently no reliable non-invasive techniques that can be used to deliver an adequate heat dose to a deep seated tumour in an organ such as the liver without risking unacceptable heating of overlying and surrounding normal tissue. The Sirtex technology uses the heat generated in small magnetic particles when exposed to a high frequency magnetic field. The particles are delivered to the tumour via arterially infused microspheres which eventually embolise the tumour vasculature. The enhanced concentration of microspheres around the tumour ensures only the diseased tissue is heated. This paper reviews the current status of this research and presents recent experimental results including the differential heating and consequent destruction of experimental animal tumours. The pathway to clinical application will be discussed in light of these results

  16. Properties of nanoparticles prepared from NdFeB-based compound for magnetic hyperthermia application.

    Périgo, E A; Silva, S C; de Sousa, E M B; Freitas, A A; Cohen, R; Nagamine, L C C M; Takiishi, H; Landgraf, F J G

    2012-05-04

    Nanoparticles were prepared from a NdFeB-based alloy using the hydrogen decrepitation process together with high-energy ball milling and tested as heating agent for magnetic hyperthermia. In the milling time range evaluated (up to 10 h), the magnetic moment per mass at H = 1.59 MA m(-1) is superior than 70 A m(2) kg(-1); however, the intrinsic coercivity might be inferior than 20 kA m(-1). The material presents both ferromagnetic and superparamagnetic particles constituted by a mixture of phases due to the incomplete disproportionation reaction of Nd(2)Fe(14)BH(x) during milling. Solutions prepared with deionized water and magnetic particles exposed to an AC magnetic field (H(max) ~ 3.7 kA m(-1) and f = 228 kHz) exhibited 26 K ≤ ΔT(max) ≤ 44 K with a maximum estimated specific absorption rate (SAR) of 225 W kg(-1). For the pure magnetic material milled for the longest period of time (10 h), the SAR was estimated as ~2500 W kg(-1). In vitro tests indicated that the powders have acceptable cytotoxicity over a wide range of concentration (0.1-100 µg ml(-1)) due to the coating applied during milling.

  17. Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia

    Wang, Q.; Deng, Z. S.; Liu, J.

    2012-01-01

    The large blood vessels surrounding the tumor would significantly result in heat sink, and thus seriously limit the thermal ablative area during tumor hyperthermia. Magnetic nanoparticle (MNP) was recently identified as an important heating enhancer to improve the treatment efficiency. It will not only help to absorb more energy under the irradiation of external magnetic field, but also can block the blood flow and subsequently weaken the heat sink effect of large vessels. In this study, these two critical factors, reserved to be undisclosed before in theory, were comprehensively investigated through three-dimensional numerical simulation. The results suggested that concerning the contribution to temperature increase in the tissues surrounding large vessel, the factor of blood flow blocking is more effective than that of energy absorption. Therefore, selective loading of MNPs to the target sites is expected to serve as a promising method to perform successful hyperthermia treatment for tumor tissues embedded with large blood vessels.

  18. Theoretical evaluations of magnetic nanoparticle-enhanced heating on tumor embedded with large blood vessels during hyperthermia

    Wang, Q. [Tsinghua University, Department of Biomedical Engineering, School of Medicine (China); Deng, Z. S. [Chinese Academy of Sciences, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry (China); Liu, J., E-mail: jliubme@tsinghua.edu.cn [Tsinghua University, Department of Biomedical Engineering, School of Medicine (China)

    2012-07-15

    The large blood vessels surrounding the tumor would significantly result in heat sink, and thus seriously limit the thermal ablative area during tumor hyperthermia. Magnetic nanoparticle (MNP) was recently identified as an important heating enhancer to improve the treatment efficiency. It will not only help to absorb more energy under the irradiation of external magnetic field, but also can block the blood flow and subsequently weaken the heat sink effect of large vessels. In this study, these two critical factors, reserved to be undisclosed before in theory, were comprehensively investigated through three-dimensional numerical simulation. The results suggested that concerning the contribution to temperature increase in the tissues surrounding large vessel, the factor of blood flow blocking is more effective than that of energy absorption. Therefore, selective loading of MNPs to the target sites is expected to serve as a promising method to perform successful hyperthermia treatment for tumor tissues embedded with large blood vessels.

  19. Synthesis of Gold Nanoparticles by Electro-reduction Method and Their Application as an Electro-hyperthermia System

    Yoon, Young Il; Kim, Kwangsoo; Kwon, Yongsoo; Cho, Heesang; Yoon, Changjin; Yoon, Taejong; Lee, Hak Jong

    2014-01-01

    We report the successful preparation of gold nanoparticles (Au NPs) using a novel electroreduction process, which is simple, fast, and environmentally friendly (toxic chemicals such as strong reducing agents are not required). Our process allows for the mass production of Au NPs and adequate particle size control. The Au NPs prepared show high biocompatibility and are non-toxic to healthy human cells. By applying radiofrequency (RF) ablation, we monitored the electro-hyperthermia effect of the Au NPs at different RFs. The Au NPs exhibit a fast increase in temperature to 55 .deg. C within 5 min during the application of an RF of 13 MHz. This temperature rise is sufficient to promote apoptosis through thermal stress. Our work suggests that the selective Au NP-mediated electro-hyperthermia therapy for tumor cells under an RF of 13 MHz has great potential as a clinical treatment for specific tumor ablation

  20. ‘Smart’ gold nanoshells for combined cancer chemotherapy and hyperthermia

    Liang, Zhongshi; Xie, Yegui; Liu, Shunying; Li, Xingui

    2014-01-01

    Nanomaterials that circulate in the body have great potential in the diagnosis and treatment of diseases. Here we report that ‘smart’ gold nanoshells can carry a drug payload, and that their intrinsic near-infrared (NIR) plasmon resonance enables the combination of chemotherapeutic and hyperthermia therapies. The ‘smart’ gold nanoshells (named DOX/A54@GNs) consist of (a) gold nanoshells (GNs) with NIR plasmon resonance, which not only act as nanoblocks but also produce local heat to allow hyperthermia; (b) an anticancer drug, doxorubicin (DOX), which was conjugated onto the nanoblocks by pH-dependent biodegradable copolymer thiol poly(ethylene glycol) derivatives via carbamate linkage; and (c) the targeting peptide A54 (AGKGTPSLETTP) to facilitate its orientation to liver cancer cells and enhance cellular uptake. The conjugated DOX was released from the DOX/A54@GNs much more rapidly in an acidic environment (pH 5.3) than in a neutral environment (pH 7.4), which is a desirable characteristic for intracellular tumor drug release. DOX-modified GNs showed pH-dependent release behavior, and the in vitro cell uptake experiment using ICP-AES and microscopy showed greater internalization of A54-modified GNs in the human liver cancer cell line BEL-7402 than of those without A54. Flow cytometry and fluoroscopy analysis were conducted to reveal the enhanced cell apoptosis caused by the A54-modified GNs under combined chemotherapeutic and hyperthermia therapies. These results imply that DOX/A54@GNs could be used as a multifunctional nanomaterial system with pH-triggered drug-releasing properties for tumor-targeted chemotherapy and hyperthermia. (paper)

  1. A new mild hyperthermia device to treat vascular involvement in cancer surgery.

    Ware, Matthew J; Nguyen, Lam P; Law, Justin J; Krzykawska-Serda, Martyna; Taylor, Kimberly M; Cao, Hop S Tran; Anderson, Andrew O; Pulikkathara, Merlyn; Newton, Jared M; Ho, Jason C; Hwang, Rosa; Rajapakshe, Kimal; Coarfa, Cristian; Huang, Shixia; Edwards, Dean; Curley, Steven A; Corr, Stuart J

    2017-09-12

    Surgical margin status in cancer surgery represents an important oncologic parameter affecting overall prognosis. The risk of disease recurrence is minimized and survival often prolonged if margin-negative resection can be accomplished during cancer surgery. Unfortunately, negative margins are not always surgically achievable due to tumor invasion into adjacent tissues or involvement of critical vasculature. Herein, we present a novel intra-operative device created to facilitate a uniform and mild heating profile to cause hyperthermic destruction of vessel-encasing tumors while safeguarding the encased vessel. We use pancreatic ductal adenocarcinoma as an in vitro and an in vivo cancer model for these studies as it is a representative model of a tumor that commonly involves major mesenteric vessels. In vitro data suggests that mild hyperthermia (41-46 °C for ten minutes) is an optimal thermal dose to induce high levels of cancer cell death, alter cancer cell's proteomic profiles and eliminate cancer stem cells while preserving non-malignant cells. In vivo and in silico data supports the well-known phenomena of a vascular heat sink effect that causes high temperature differentials through tissues undergoing hyperthermia, however temperatures can be predicted and used as a tool for the surgeon to adjust thermal doses delivered for various tumor margins.

  2. Manganese doped-iron oxide nanoparticle clusters and their potential as agents for magnetic resonance imaging and hyperthermia

    Casula, Maria F.

    2016-06-10

    A simple, one pot method to synthesize water-dispersible Mn doped iron oxide colloidal clusters constructed of nanoparticles arranged into secondary flower-like structures was developed. This method allows the successful incorporation and homogeneous distribution of Mn within the nanoparticle iron oxide clusters. The formed clusters retain the desired morphological and structural features observed for pure iron oxide clusters, but possess intrinsic magnetic properties that arise from Mn doping. They show distinct performance as imaging contrast agents and excellent characteristics as heating mediators in magnetic fluid hyperthermia. It is expected that the outcomes of this study will open up new avenues for the exploitation of doped magnetic nanoparticle assemblies in biomedicine. © the Owner Societies 2016.

  3. Manganese doped-iron oxide nanoparticle clusters and their potential as agents for magnetic resonance imaging and hyperthermia

    Casula, Maria F.; Conca, Erika; Bakaimi, Ioanna; Sathya, Ayyappan; Materia, Maria Elena; Casu, Alberto; Falqui, Andrea; Sogne, Elisa; Pellegrino, Teresa; Kanaras, Antonios G.

    2016-01-01

    A simple, one pot method to synthesize water-dispersible Mn doped iron oxide colloidal clusters constructed of nanoparticles arranged into secondary flower-like structures was developed. This method allows the successful incorporation and homogeneous distribution of Mn within the nanoparticle iron oxide clusters. The formed clusters retain the desired morphological and structural features observed for pure iron oxide clusters, but possess intrinsic magnetic properties that arise from Mn doping. They show distinct performance as imaging contrast agents and excellent characteristics as heating mediators in magnetic fluid hyperthermia. It is expected that the outcomes of this study will open up new avenues for the exploitation of doped magnetic nanoparticle assemblies in biomedicine. © the Owner Societies 2016.

  4. Prospective phase II trial of regional hyperthermia and whole liver irradiation for numerous chemorefratory liver metastases from colerectal cancer

    Yu, Jeong Il; Park, Hee Chul; Choi, Doo Ho [Dept. of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); and others

    2016-03-15

    A prospective phase II trial was conducted to evaluate the effectiveness and toxicity of regional hyperthermia and whole liver irradiation (WLI) for numerous chemorefractory liver metastases from colorectal cancer. Enrolled patients had numerous chemorefractory hepatic metastases from colorectal cancer. Five sessions of hyperthermia and seven fractions of 3-gray WLI were planned. Health-related quality of life (HRQoL) was determined using the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire C-30 and the Functional Assessment of Cancer Therapy-Hepatobiliary version 4.0. Objective and pain response was evaluated. A total of 12 patients consented to the study and the 10 who received WLI and hyperthermia were analyzed. WLI was completed as planned in nine patients and hyperthermia in eight. Pain response was partial in four patients and stable in four. Partial objective response was achieved in three patients (30.0%) and stable disease was seen in four patients at the 1-month follow-up. One patient died 1 month after treatment because of respiratory failure related to pleural metastasis progression. Other grade III or higher toxicities were detected in three patients; however, all severe toxicities were related to disease progression rather than treatment. No significant difference in HRQoL was noted at the time of assessment for patients who were available for questionnaires. Combined WLI and hyperthermia were well tolerated without severe treatment-related toxicity with a promising response from numerous chemorefractory hepatic metastases from colorectal cancer.

  5. Iron oxide and gold nanoparticles in cancer therapy

    Gotman, Irena, E-mail: gotman@technion.ac.il; Gutmanas, Elazar Y., E-mail: gutmanas@technion.ac.il [Department of Materials Science and Engineering, Technion-Israel Institute of Technology, Haifa, 32000 Israel (Israel); Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Psakhie, Sergey G. [Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation); Institute of Strength Physics and Materials Science SB RAS, Tomsk, 634055 (Russian Federation); Lozhkomoev, Aleksandr S. [Tomsk Polytechnic University, Tomsk, 634050 (Russian Federation)

    2016-08-02

    Continuous research activities in the field of nanomedicine in the past decade have, to a great extent, been focused on nanoparticle technologies for cancer therapy. Gold and iron oxide nanoparticles (NP) are two of the most studied inorganic nanomaterials due to their unique optical and magnetic properties. Both types of NPs are emerging as promising systems for anti-tumor drug delivery and for nanoparticle-mediated thermal therapy of cancer. In thermal therapy, localized heating inside tumors or in proximity of tumor cells can be induced, for example, with Au NPs by radiofrequency ablation heating or conversion of photon energy (photothermal therapy) and in iron oxide magnetic NPs by heat generation through relaxation in an alternating magnetic field (magnetic hyperthermia). Furthermore, the superparamagnetic properties of iron oxide nanoparticles have led to their use as potent MRI (magnetic resonance imaging) contrast agents. Surface modification/coating can produce NPs with tailored and desired properties, such as enhanced blood circulation time, stability, biocompatibility and water solubility. To target nanoparticles to specific tumor cells, NPs should be conjugated with targeting moieties on the surface which bind to receptors or other molecular structures on the cell surface. The article presents several approaches to enhancing the specificity of Au and iron oxide nanoparticles for tumor tissue by appropriate surface modification/functionalization, as well as the effect of these treatments on the saturation magnetization value of iron oxide NPs. The use of other nanoparticles and nanostructures in cancer treatment is also briefly reviewed.

  6. A wide-frequency range AC magnetometer to measure the specific absorption rate in nanoparticles for magnetic hyperthermia

    Garaio, E.; Collantes, J.M.; Garcia, J.A.; Plazaola, F.; Mornet, S.; Couillaud, F.; Sandre, O.

    2014-01-01

    Measurement of specific absorption rate (SAR) of magnetic nanoparticles is crucial to assert their potential for magnetic hyperthermia. To perform this task, calorimetric methods are widely used. However, those methods are not very accurate and are difficult to standardize. In this paper, we present AC magnetometry results performed with a lab-made magnetometer that is able to obtain dynamic hysteresis-loops in the AC magnetic field frequency range from 50 kHz to 1 MHz and intensities up to 24 kA m −1 . In this work, SAR values of maghemite nanoparticles dispersed in water are measured by AC magnetometry. The so-obtained values are compared with the SAR measured by calorimetric methods. Both measurements, by calorimetry and magnetometry, are in good agreement. Therefore, the presented AC magnetometer is a suitable way to obtain SAR values of magnetic nanoparticles. - Highlights: • We propose AC magnetometry as a method to measure the specific absorption rate (SAR) of magnetic nanoparticles suitable for magnetic hyperthermia therapy. • We have built a lab-made AC magnetometer, which is able to measure magnetic dynamic hysteresis-loops of nanoparticle dispersions. • The device works with AC magnetic field intensities up to 24 kA m −1 in a frequency range from 75 kHz to 1 MHz. • The SAR values of maghemite nanoparticles around 12 nm in magnetic diameter dispersed in water are measured by the lab-made magnetometer and different calorimetric methods. • Although all methods are in good agreement, several factors (probe location, thermal inertia, losses, etc.) make calorimetric method less accurate than AC magnetometry

  7. Folic acid-conjugated Fe3O4 magnetic nanoparticles for hyperthermia and MRI in vitro and in vivo

    Jiang, Q.L.; Zheng, S.W.; Hong, R.Y.; Deng, S.M.; Guo, L.; Hu, R.L.; Gao, B.; Huang, M.; Cheng, L.F.; Liu, G.H.; Wang, Y.Q.

    2014-01-01

    The folic acid (FA)-conjugated Fe 3 O 4 magnetic nanoparticles (MNPs) were synthesized by co-precipitation of Fe 3+ and Fe 2+ solution followed by surface modification with carboxymethyl dextran (CMD) to form carboxymethyl group terminated MNPs, then FA was conjugated with the carboxyl group functionalized MNPs. The morphology and properties of obtained nanoparticles were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), UV–visible spectra (UV–vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), vibrating sample magnetometer (VSM) and thermogravimetric analysis (TGA). The FA-conjugated MNPs exhibited relatively high saturation magnetization and fast magneto-temperature response which could be applied to hyperthermia therapy. To determine the accurate targeting effect of FA, we chose FA-conjugated MNPs as MRI contrast enhancement agent for detection of KB cells with folate receptor over-expression in vitro and in vivo. The results show that these magnetic nanoparticles appear to be the promising materials for local hyperthermia and MRI.

  8. Nano-magnetite coated with gold: alternative oncological therapy with magnetic hyperthermia

    Cordova F, T.; Jimenez G, O.; Basurto I, G.; Martinez E, J. C.

    2017-10-01

    Localized hyperthermia performed through the use of nanoparticles is one of the most promising procedures for the cancer treatment. In this work, the synthesis of magnetite nanoparticles (Fe 2 O 3 ) was carried out using the thermal decomposition method. Subsequently, these nanoparticles were coated with gold and suspended in aqueous phase. As a result, nanoparticles capable of being heated by the application of an alternating magnetic field or through the use of infrared radiation were obtained. As an additional feature, these nanoparticles are biocompatible thanks to their golden coating. The synthesized nanoparticles can be functionalized by the conjugation of a molecule (aptamer, antibody, peptide, etc.) whose target is a cancer cell in order to adhere to it the nanoparticle-marker complex, to subsequently carry out a heating with the objective of induce cell death. In conclusion, the synthesized nanoparticles allow providing an alternative treatment for cancer through the use of localized hyperthermia, either using magnetic or infrared heating. (Author)

  9. Long-Term Improvement in Treatment Outcome After Radiotherapy and Hyperthermia in Locoregionally Advanced Cervix Cancer: An Update of the Dutch Deep Hyperthermia Trial

    Franckena, Martine; Stalpers, Lukas J.A.; Koper, Peter C.M.; Wiggenraad, Ruud G.J.; Hoogenraad, Wim J.; Dijk, Jan D.P. van; Warlam-Rodenhuis, Carla C.; Jobsen, Jan J.; Rhoon, Gerard C. van; Zee, Jacoba van der

    2008-01-01

    Purpose: The local failure rate in patients with locoregionally advanced cervical cancer is 41-72% after radiotherapy (RT) alone, whereas local control is a prerequisite for cure. The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia (HT) improved 3-year local control rates of 41-61%, as we reported earlier. In this study, we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up. Methods and Materials: From 1990 to 1996, a total of 114 women with locoregionally advanced cervical carcinoma were randomly assigned to RT or RT + HT. The RT was applied to a median total dose of 68 Gy. The HT was given once weekly. The primary end point was local control. Secondary end points were overall survival and late toxicity. Results: At the 12-year follow-up, local control remained better in the RT + HT group (37% vs. 56%; p = 0.01). Survival was persistently better after 12 years: 20% (RT) and 37% (RT + HT; p = 0.03). World Health Organization (WHO) performance status was a significant prognostic factor for local control. The WHO performance status, International Federation of Gynaecology and Obstetrics (FIGO) stage, and tumor diameter were significant for survival. The benefit of HT remained significant after correction for these factors. European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups. Conclusions: For locoregionally advanced cervical cancer, the addition of HT to RT resulted in long-term major improvement in local control and survival without increasing late toxicity. This combined treatment should be considered for patients who are unfit to receive chemotherapy. For other patients, the optimal treatment strategy is the subject of ongoing research

  10. Targeted nanoparticles for colorectal cancer

    Cisterna, Bruno A.; Kamaly, Nazila; Choi, Won Il

    2016-01-01

    Colorectal cancer (CRC) is highly prevalent worldwide, and despite notable progress in treatment still leads to significant morbidity and mortality. The use of nanoparticles as a drug delivery system has become one of the most promising strategies for cancer therapy. Targeted nanoparticles could...

  11. Improved delivery of magnetic nanoparticles with chemotherapy cancer treatment

    Petryk, Alicia A.; Giustini, Andrew J.; Gottesman, Rachel E.; Hoopes, P. Jack

    2013-02-01

    Most nanoparticle-based cancer therapeutic strategies seek to develop an effective individual cancer cell or metastatic tumor treatment. Critical to the success of these therapies is to direct as much of the agent as possible to the targeted tissue while avoiding unacceptable normal tissue complications. In this light, three different cisplatinum/magnetic nanoparticle (mNP) administration regimens were investigated. The most important finding suggests that clinically relevant doses of cisplatinum result in a significant increase in the tumor uptake of systemically delivered mNP. This enhancement of mNP tumor uptake creates the potential for an even greater therapeutic ratio through the addition of mNP based, intracellular hyperthermia.

  12. Hyperthermia enhances radiosensitivity of colorectal cancer cells through ROS inducing autophagic cell death.

    Ba, Ming-Chen; Long, Hui; Wang, Shuai; Wu, Yin-Bing; Zhang, Bo-Huo; Yan, Zhao-Fei; Yu, Fei-Hong; Cui, Shu-Zhong

    2018-04-01

    Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC). After four weeks of treatment, cancer growth inhibition, rate and mitochondrial membrane potential were measured with MTT and JC-1 assays, respectively, while ROS were estimated fluorimetrically. The relationship of these parameters to expressions of autophagy-related genes Beclin1, LC3B, and mTOR was analyzed. Gene expression was measured by Real-Time polymerase chain reaction (RT-PCR). There were significant increases in ROS levels and mitochondrial membrane potential in the HT + RT group. ROS levels in the HT + RT group increased more significantly than in any other group. In contrast, ROS levels in the HT + RT + NAC group were significantly decreased relative to the HT + RT group. The number of autophagic bodies in HT + RT group was higher than that of mock group. There were significant increases in the expression of Beclin1 and LC3B genes, while mTOR expression was significantly decreased in the HT + CT group. Treatment with NAC reversed the pattern of these changes. These results indicate that HT enhances the radiosensitivity of colorectal cancer cells to RT through ROS inducing autophagic cell death. © 2017 Wiley Periodicals, Inc.

  13. Gold nanoparticles for cancer detection and treatment: The role of adhesion

    Oni, Y.; Hao, K.; Dozie-Nwachukwu, S.; Odusanya, O. S.; Obayemi, J.D.; Anuku, N.; Soboyejo, W. O.

    2014-01-01

    This paper presents the results of an experimental study of the effects of adhesion between gold nanoparticles and surfaces that are relevant to the potential applications in cancer detection and treatment. Adhesion is measured using a dip coating/atomic force microscopy (DC/AFM) technique. The adhesion forces are obtained for dip-coated gold nanoparticles that interact with peptide or antibody-based molecular recognition units (MRUs) that attach specifically to breast cancer cells. They include MRUs that attach specifically to receptors on breast cancer cells. Adhesion forces between anti-cancer drugs such as paclitaxel, and the constituents of MRU-conjugated Au nanoparticle clusters, are measured using force microscopy techniques. The implications of the results are then discussed for the design of robust gold nanoparticle clusters and for potential applications in localized drug delivery and hyperthermia

  14. Gold nanoparticles for cancer detection and treatment: The role of adhesion

    Oni, Y. [Princeton Institute for Science and Technology of Materials (PRISM), Princeton University, 70 Prospect Street, Princeton, New Jersey 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544 (United States); Hao, K. [Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 (United States); Dozie-Nwachukwu, S.; Odusanya, O. S. [African University of Science and Technology (AUST), Kilometer 10, Airport Road, Abuja, Federal Capital Territory (Nigeria); Sheda Science and Technology Complex (SHESTCO), Gwagwalada, Abuja, Federal Capital Territory (Nigeria); Obayemi, J.D. [African University of Science and Technology (AUST), Kilometer 10, Airport Road, Abuja, Federal Capital Territory (Nigeria); Anuku, N. [Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544 (United States); Department of Chemistry and Chemical Technology, Bronx Community College, New York, New York 10453 (United States); Soboyejo, W. O. [Princeton Institute for Science and Technology of Materials (PRISM), Princeton University, 70 Prospect Street, Princeton, New Jersey 08544 (United States); Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544 (United States); African University of Science and Technology (AUST), Kilometer 10, Airport Road, Abuja, Federal Capital Territory (Nigeria)

    2014-02-28

    This paper presents the results of an experimental study of the effects of adhesion between gold nanoparticles and surfaces that are relevant to the potential applications in cancer detection and treatment. Adhesion is measured using a dip coating/atomic force microscopy (DC/AFM) technique. The adhesion forces are obtained for dip-coated gold nanoparticles that interact with peptide or antibody-based molecular recognition units (MRUs) that attach specifically to breast cancer cells. They include MRUs that attach specifically to receptors on breast cancer cells. Adhesion forces between anti-cancer drugs such as paclitaxel, and the constituents of MRU-conjugated Au nanoparticle clusters, are measured using force microscopy techniques. The implications of the results are then discussed for the design of robust gold nanoparticle clusters and for potential applications in localized drug delivery and hyperthermia.

  15. Radionuclide investigations of the hormonal reflection of warm stress in cancer patients under whole body guided hyperthermia

    Prokhorova, V.I.; Zhavrid, Eh.A.; Fradkin, S.Z.; Tsyrus', T.P.; Shitikov, B.D.; Kosheleva, M.I.

    1991-01-01

    The results of the radioimmunoassay of ACTH, ST, hydrocortisone, glucagon, C-peptide, insulin and cyclic nucleotides in 180 patients with advanced and metastatic melanomas, soft tissue sarcomas, lung cancers and renal cell carcinomas testify to the development of the syndrome of endocrine hyperfunction in patients under whole-body guided hyperthermia and artificial hyperglycemia as well as of functional pancreas insufficiency. The data presented form a biochemical basis for working out measures to optimally carry out whole-body hyperthermia and artificial hyperglycemia treatment, aimed at increasing the range of indications for its use in clinical oncology

  16. THE FIRST EXPERIENCE OF USING LOCAL HYPERTHERMIA IN COMBINED MODALITY TREATMENT OF OPERABLE NON-SMALL CELL LUNG CANCER

    A. Yu. Dobrodeev

    2015-01-01

    Full Text Available The paper presents the first experience in treating 5 patients with stage II–III non-small cell lung cancer using combined modality treatment including 40 Gy preoperative hyperfractionated radiotherapy with concurrent 2 cycles of paclitaxel/carboplatin chemotherapy and local hyperthermia (10 sessions followed by radical surgery. The overal response rate to preoperative treatment was 80 %. Chemotherapy was well tolerated and hyperthermia resulted no in adverse effects. All patients underwent surgery (4 lobectomies and 1 pneumonectomy. No complications were observed in the postoperative period. The follow-up period ranged from 6 to 20 months. No evidence of disease progression and radiation-induced damages were observed.

  17. Threshold heating temperature for magnetic hyperthermia: Controlling the heat exchange with the blocking temperature of magnetic nanoparticles

    Pimentel, B.; Caraballo-Vivas, R. J.; Checca, N. R.; Zverev, V. I.; Salakhova, R. T.; Makarova, L. A.; Pyatakov, A. P.; Perov, N. S.; Tishin, A. M.; Shtil, A. A.; Rossi, A. L.; Reis, M. S.

    2018-04-01

    La0.75Sr0.25MnO3 nanoparticles with average diameter close to 20.9 nm were synthesized using a sol-gel method. Measurements showed that the heating process stops at the blocking temperaturesignificantly below the Curie temperature. Measurements of Specific Absorption Rate (SAR) as a function of AC magnetic field revealed a superquadratic power law, indicating that, in addition to usual Néel and Brown relaxation, the hysteresis also plays an important role in the mechanism of heating. The ability to control the threshold heating temperature, a low remanent magnetization and a low field needed to achieve the magnetic saturation are the advantages of this material for therapeutic magnetic hyperthermia.

  18. Magnetic Hyperthermia and Radiation Therapy: Radiobiological Principles and Current Practice †

    Spiridon V. Spirou

    2018-06-01

    Full Text Available Hyperthermia, though by itself generally non-curative for cancer, can significantly increase the efficacy of radiation therapy, as demonstrated by in vitro, in vivo, and clinical results. Its limited use in the clinic is mainly due to various practical implementation difficulties, the most important being how to adequately heat the tumor, especially deep-seated ones. In this work, we first review the effects of hyperthermia on tissue, the limitations of radiation therapy and the radiobiological rationale for combining the two treatment modalities. Subsequently, we review the theory and evidence for magnetic hyperthermia that is based on magnetic nanoparticles, its advantages compared with other methods of hyperthermia, and how it can be used to overcome the problems associated with traditional techniques of hyperthermia.

  19. Conventional and microwave combustion synthesis of optomagnetic CuFe2O4 nanoparticles for hyperthermia studies

    Kombaiah, K.; Vijaya, J. Judith; Kennedy, L. John; Bououdina, M.; Al-Najar, Basma

    2018-04-01

    Nanosized copper ferrite (CuFe2O4) nanoparticles have been prepared by conventional (CCM) and microwave (MCM) combustion methods using Hibiscus rosa sinensis plant extract as a fuel. XRD and rietveld analysis confirmed the formation of single cubic phase and with crystallite size varying from 25 to 62 nm owing to grain growth after calcination. FT-IR analysis confirms the modes of the cubic CuFe2O4 phase, due to the stretching and bending vibrations. Spherical shaped particles are observed by scanning electron microscopy and the average particle size is found to be in the range of 50-200 nm. The chemical composition is confirmed by energy dispersive X-ray analysis. The optical band gap energy estimated using Kubelka-Munk function with the help of UV-Visible diffused reflectance spectroscopy, is found to be 2.34 and 2.22 eV for CCM and MCM respectively. Photoluminescence analysis indicates that both samples absorb light in the UV-visible region and exhibit emissions at 360, 376, and 412 nm. Magnetic measurements indicate a ferromagnetic behavior, where both magnetic properties very much influenced by the preparation method and calcination temperature: both saturation magnetization and coercivity are found higher when using CCM and MCM; from 29.40 to 34.09 emu/g while almost double from 224.4 to 432.2 Oe. The observed changes in physical properties are mainly associated with crystallinity, particle size, better chemical homogeneity, and cations distribution among tetrahedral/octahedral sites. The maximum specific absorption rate obtained was 14.63 W/g, which can be considered suitable and favorable for magnetic hyperthermia. This study highlighted the benefits of green synthesis of CuFe2O4 nanoparticles providing better magnetic properties for the platform of hyperthermia application.

  20. Hyperthermia quality assurance

    Shrivastava, P.N.; Paliwal, B.R.

    1984-01-01

    Hyperthermia Physics Center (HPC) operating under contract with the National Cancer Institute is developing a Quality Assurance program for local and regional hyperthermia. The major clinical problem in hyperthermia treatments is that they are extremely difficult to plan, execute, monitor and reproduce. A scientific basis for treatment planning can be established only after ensuring that the performance of heat generating and temperature monitoring systems are reliable. The HPC is presently concentrating on providing uniform NBS traceable calibration of thermometers and evaluation of reproducibility for power generator operation, applicator performance, phanta compositions, system calibrations and personnel shielding. The organizational plan together with recommended evaluation measurements, procedures and criteria are presented

  1. Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation

    Chu, William, E-mail: William.Chu@sunnybrook.ca [Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario (Canada); Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Staruch, Robert M. [Clinical Sites Research Program, Philips Research, Cambridge, Massachusetts (United States); Pichardo, Samuel [Thunder Bay Regional Research Institute, Thunder Bay, Ontario (Canada); Physics and Electrical Engineering, Lakehead University, Thunder Bay, Ontario (Canada); Tillander, Matti; Köhler, Max O. [MR Therapy, Philips Healthcare, Vantaa (Finland); Huang, Yuexi [Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Ylihautala, Mika [MR Therapy, Philips Healthcare, Vantaa (Finland); McGuffin, Merrylee [Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario (Canada); Czarnota, Gregory [Department of Radiation Oncology, Sunnybrook Health Sciences Centre and the University of Toronto, Toronto, Ontario (Canada); Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada); Hynynen, Kullervo [Physical Sciences, Sunnybrook Research Institute, Toronto, Ontario (Canada)

    2016-07-15

    Purpose: To evaluate the feasibility of magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. Methods and Materials: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. Results: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. Conclusions: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.

  2. Magnetic Resonance–Guided High-Intensity Focused Ultrasound Hyperthermia for Recurrent Rectal Cancer: MR Thermometry Evaluation and Preclinical Validation

    Chu, William; Staruch, Robert M.; Pichardo, Samuel; Tillander, Matti; Köhler, Max O.; Huang, Yuexi; Ylihautala, Mika; McGuffin, Merrylee; Czarnota, Gregory; Hynynen, Kullervo

    2016-01-01

    Purpose: To evaluate the feasibility of magnetic resonance–guided high-intensity focused ultrasound (MR-HIFU) mild hyperthermia in deep tissue targets for enhancing radiation therapy and chemotherapy in the context of recurrent rectal cancer. A preclinical study was performed to evaluate the safety and performance of MR-HIFU mild hyperthermia. A prospective imaging study was performed in volunteers with rectal cancer to evaluate MR thermometry quality near the rectum and accessibility of rectal tumors using MR-HIFU. Methods and Materials: Mild hyperthermia was performed in pig thigh (9 sonications, 6 pigs) using a clinical MR-HIFU system. Targets near the rectal wall and deep thigh were evaluated. Thermal maps obtained in 6 planes every 3.2 seconds were used to control sonications in 18-mm diameter treatment regions at temperatures of 42°C to 42.5°C for 10 to 60 minutes. Volunteer imaging-only studies to assess the quality of MR thermometry (without heating) were approved by the institutional research ethics board. Anatomic and MR thermometry images were acquired in consenting volunteers with rectal cancer. In 3 of 6 study participants, rectal filling with saline was used to reduce motion-related MR thermometry artifacts near the tumor. Results: In pigs, mean target temperature matched the desired hyperthermia temperature within 0.2°C; temporal standard deviation ≤0.5°C. With optimized control thresholds, no undesired tissue damage was observed. In human volunteers, MR temperature measurements had adequate precision and stability, especially when rectal filling was used to reduce bowel motion. Conclusions: In pigs, MR-HIFU can safely deliver mild hyperthermia (41°C-43°C) to a targeted volume for 30 minutes. In humans, careful patient selection and preparation will enable adequate targeting for recurrent rectal cancers and sufficient MR temperature mapping stability to control mild hyperthermia. These results enable human trials of MR-HIFU hyperthermia.

  3. Nanomedicine for cancer therapy from chemotherapeutic to hyperthermia-based therapy

    Kumar, Piyush

    2017-01-01

    This Brief focuses on the cancer therapy available till date, from conventional drug delivery to nanomedicine in clinical trial. In addition, it reports on future generation based nanotherapeutics and cancer theranostic agent for effective therapeutic diagnosis and treatment. Breast cancer was chosen as the model system in this review. The authors give emphasis to multiple drug resistance (MDR) and its mechanism and how to overcome it using the nanoparticle approach. .

  4. Hyperthermia enhances mapatumumab-induced apoptotic death through ubiquitin-mediated degradation of cellular FLIP(long) in human colon cancer cells.

    Song, X; Kim, S-Y; Zhou, Z; Lagasse, E; Kwon, Y T; Lee, Y J

    2013-04-04

    Colorectal cancer is the third leading cause of cancer-related mortality in the world; the main cause of death of colorectal cancer is hepatic metastases, which can be treated with hyperthermia using isolated hepatic perfusion (IHP). In this study, we report that mild hyperthermia potently reduced cellular FLIP(long), (c-FLIP(L)), a major regulator of the death receptor (DR) pathway of apoptosis, thereby enhancing humanized anti-DR4 antibody mapatumumab (Mapa)-mediated mitochondria-independent apoptosis. We observed that overexpression of c-FLIP(L) in CX-1 cells abrogated the synergistic effect of Mapa and hyperthermia, whereas silencing of c-FLIP in CX-1 cells enhanced Mapa-induced apoptosis. Hyperthermia altered c-FLIP(L) protein stability without concomitant reductions in FLIP mRNA. Ubiquitination of c-FLIP(L) was increased by hyperthermia, and proteasome inhibitor MG132 prevented heat-induced downregulation of c-FLIP(L). These results suggest the involvement of the ubiquitin-proteasome system in this process. We also found lysine residue 195 (K195) to be essential for c-FLIP(L) ubiquitination and proteolysis, as mutant c-FLIP(L) lysine 195 arginine (arginine replacing lysine) was left virtually un-ubiquitinated and was refractory to hyperthermia-triggered degradation, and thus partially blocked the synergistic effect of Mapa and hyperthermia. Our observations reveal that hyperthermia transiently reduced c-FLIP(L) by proteolysis linked to K195 ubiquitination, which contributed to the synergistic effect between Mapa and hyperthermia. This study supports the application of hyperthermia combined with other regimens to treat colorectal hepatic metastases.

  5. Hyperthermia-enhanced TRAIL- and mapatumumab-induced apoptotic death is mediated through mitochondria in human colon cancer cells.

    Song, Xinxin; Kim, Han-Cheon; Kim, Seog-Young; Basse, Per; Park, Bae-Hang; Lee, Byeong-Chel; Lee, Yong J

    2012-05-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world; death usually results from uncontrolled metastatic disease. Previously, we developed a novel strategy of TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) in combination with hyperthermia to treat hepatic colorectal metastases. However, previous studies suggest a potential hepatocyte cytotoxicity with TRAIL. Unlike TRAIL, anti-human TRAIL receptor antibody induces apoptosis without hepatocyte toxicity. In this study, we evaluated the anti-tumor efficacy of humanized anti-death receptor 4 (DR4) antibody mapatumumab (Mapa) by comparing it with TRAIL in combination with hyperthermia. TRAIL, which binds to both DR4 and death receptor 5 (DR5), was approximately tenfold more effective than Mapa in inducing apoptosis. However, hyperthermia enhances apoptosis induced by either agent. We observed that the synergistic effect was mediated through elevation of reactive oxygen species, c-Jun N-terminal kinase activation, Bax oligomerization, and translocalization to the mitochondria, loss of mitochondrial membrane potential, release of cytochrome c to cytosol, activation of caspases, and increase in poly(ADP-ribose) polymerase cleavage. We believe that the successful outcome of this study will support the application of Mapa in combination with hyperthermia to colorectal hepatic metastases. Copyright © 2011 Wiley Periodicals, Inc.

  6. Intraoperative radio-frequency capacitive hyperthermia and radiation therapy for unresectable pancreatic cancer

    Nakazawa, M.; Yamashita, T.; Hashida, I.

    1988-01-01

    The authors have initiated intraoperative radiation therapy (IORT) and intraoperative radio-frequency capacitive hyperthermia (IOHT) for unresectable pancreatic cancer. After gastric (corpus) resection, IORT and IOHT were conducted and gastro-duodenostomy was performed IORT was delivered with 12 meV electron (25 Gy) and 10 MV Linac x-ray (7.5 Gy). IOHT was done with 13.56 MHz capacitive equipment aiming 43 0 C for over 30 min along with concurrent administration of 500 mg 5-FU. Five cases were heated by the conventional method and two additional cases were heated with a newly fabricated applicator. Attained temperatures monitored directly from tumor were 38.5 0 C-44.3 0 C (over 43 0 C in four cases, 40 0 C in one case, and below 40 0 C in two cass.) Pain relief was achieved in most cases. Using the new applicators, the authors could avoid unexpected hot spots and insufficient heating

  7. Mathematical modelling of the destruction degree of cancer under the influence of a RF hyperthermia

    Paruch, Marek; Turchan, Łukasz

    2018-01-01

    The article presents the mathematical modeling of the phenomenon of artificial hyperthermia which is caused by the interaction of an electric field. The electric field is induced by the applicator positioned within the biological tissue with cancer. In addition, in order to estimate the degree of tumor destruction under the influence of high temperature an Arrhenius integral has been used. The distribution of electric potential in the domain considered is described by the Laplace system of equations, while the temperature field is described by the Pennes system of equations. These problems are coupled by source function being the additional component in the Pennes equation and resulting from the electric field action. The boundary element method is applied to solve the coupled problem connected with the heating of biological tissues.

  8. A method to obtain the thermal parameters and the photothermal transduction efficiency in an optical hyperthermia device based on laser irradiation of gold nanoparticles.

    Sánchez López de Pablo, Cristina; Olmedo, José Javier Serrano; Rosales, Alejandra Mina; Ramírez Hernández, Norma; Del Pozo Guerrero, Francisco

    2014-01-01

    Optical hyperthermia systems based on the laser irradiation of gold nanorods seem to be a promising tool in the development of therapies against cancer. After a proof of concept in which the authors demonstrated the efficiency of this kind of systems, a modeling process based on an equivalent thermal-electric circuit has been carried out to determine the thermal parameters of the system and an energy balance obtained from the time-dependent heating and cooling temperature curves of the irradiated samples in order to obtain the photothermal transduction efficiency. By knowing this parameter, it is possible to increase the effectiveness of the treatments, thanks to the possibility of predicting the response of the device depending on the working configuration. As an example, the thermal behavior of two different kinds of nanoparticles is compared. The results show that, under identical conditions, the use of PEGylated gold nanorods allows for a more efficient heating compared with bare nanorods, and therefore, it results in a more effective therapy.

  9. Core-shell La.sub.1-x./sub.Sr.sub.x./sub.MnO.sub.3./sub. nanoparticles as colloidal mediators for magnetic fluid hyperthermia

    Pollert, Emil; Kaman, Ondřej; Veverka, Pavel; Veverka, Miroslav; Maryško, Miroslav; Závěta, Karel; Kačenka, M.; Lukeš, I.; Jendelová, Pavla; Kašpar, P.; Burián, M.; Herynek, V.

    2010-01-01

    Roč. 368, č. 1927 (2010), s. 4389-4405 ISSN 1364-503X R&D Projects: GA AV ČR KAN200200651; GA AV ČR KAN201110651 Institutional research plan: CEZ:AV0Z10100521; CEZ:AV0Z50390512 Keywords : magnetic fluid hyperthermia * manganese perovskites * nanoparticles Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.457, year: 2010

  10. Rib fractures after reirradiation plus hyperthermia for recurrent breast cancer. Predictive factors

    Oldenborg, Sabine; Valk, Christel; Os, Rob van; Voerde Sive Voerding, Paul zum; Crezee, Hans; Tienhoven, Geertjan van; Rasch, Coen; Oei, Bing; Venselaar, Jack; Randen, Adrienne van

    2016-01-01

    Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors on the occurrence of rib fractures. From 1982-2005, 234 patients were treated with adjuvant reRT + HT after surgery for LR. ReRT consisted typically of 8 fractions of 4 Gy twice a week, or 12 fractions of 3 Gy four times a week. A total of 118 patients were irradiated with abutted photon and electron fields. In all, 60 patients were irradiated using either one or alternating combinations of abutted AP electron fields. Hyperthermia was given once or twice a week. The 5-year infield local control (LC) rate was 70 %. Rib fractures were detected in 16 of 234 patients (actuarial risk: 7 % at 5 years). All rib fractures occurred in patients treated with a combination of photon and abutted electron fields (p = 0.000); in 15 of 16 patients fractures were located in the abutment regions. The other significant predictive factors for rib fractures were a higher fraction dose (p = 0.040), large RT fields, and treatment before the year 2000. ReRT + HT results in long-term LC. The majority of rib fractures were located in the photon/electron abutment area, emphasizing the disadvantage of field overlap. Large abutted photon/electron fields combined with 4 Gy fractions increase the number of rib fractures in this study group. However, as these factors were highly correlated no relative importance of the individual factors could be estimated. Increasing the number of HT sessions a week does not increase the risk of rib fractures. (orig.) [de

  11. Preoperative radiochemotherapy in locally advanced or recurrent rectal cancer: regional radiofrequency hyperthermia correlates with clinical parameters

    Rau, B.; Wust, P.; Tilly, W.; Gellermann, J.; Harder, C.; Riess, H.; Budach, V.; Felix, R.; Schlag, P.M.

    2000-01-01

    Purpose: Preoperative radiochemotherapy (RCT) is a widely used means of treatment for patients suffering from primary, locally advanced, or recurrent rectal cancer. We evaluated the efficacy of treatment due to additional application of regional hyperthermia (HRCT) to this conventional therapy regime in a Phase II study, employing the annular phased-array system BSD-2000 (SIGMA-60 applicator). The clinical results of the trial were encouraging. We investigated the relationship between a variety of thermal and clinical parameters in order to assess the adequacy of thermometry, the effectiveness of hyperthermia therapy, and its potential contribution to clinical endpoints. Methods and Materials: A preoperative combination of radiotherapy (1.8 Gy for 5 days a week, total dose 45 Gy applied over 5 weeks) and chemotherapy (low-dose 5-fluorouracil [5-FU] plus leucovorin in the first and fourth week) was administered to 37 patients with primary rectal cancer (PRC) and 18 patients with recurrent rectal cancer (RRC). Regional hyperthermia (RHT) was applied once a week prior to the daily irradiation fraction of 1.8 Gy. Temperatures were registered along rectal catheters using Bowman thermistors. Measurement points related to the tumor were specified after estimating the section of the catheter in near contact with the tumor. Three patients with local recurrence after abdominoperineal resection, had their catheters positioned transgluteally under CT guidance, where the section of the catheter related to the tumor was estimated from the CT scans. Index temperatures (especially T max , T 90 ) averaged over time, cumulative minutes (cum min) (here for T 90 > reference temperature 40.5 deg. C), and equivalent minutes (equ min) (with respect to 43 deg. C) were derived from repetitive temperature-position scans (5- to 10-min intervals) utilizing software specially developed for this purpose on a PC platform. Using the statistical software package SPSS a careful analysis was

  12. Association of rectal toxicity with thermal dose parameters in treatment of locally advanced prostate cancer with radiation and hyperthermia

    Hurwitz, Mark D.; Kaplan, Irving D.; Hansen, Jorgen L.; Prokopios-Davos, Savina; Topulos, George P.; Wishnow, Kenneth; Manola, Judith; Bornstein, Bruce A.; Hynynen, Kullervo

    2002-01-01

    Purpose: Although hyperthermia has been used for more than two decades in the treatment of pelvic tumors, little is known about the potential impact of heat on rectal toxicity when combined with other treatment modalities. Because rectal toxicity is a concern with radiation and may be exacerbated by hyperthermia, definition of the association of thermal dose parameters with rectal toxicity is important. In this report, we correlate rectal toxicity with thermal dose parameters for patients treated with hyperthermia and radiation for prostate cancer. Methods and Materials: Thirty patients with T2b-T3b disease (1992 American Joint Committee On Cancer criteria) enrolled in a Phase II study of external beam radiation ± androgen-suppressive therapy with two transrectal ultrasound hyperthermia treatments were assessed for rectal toxicity. Prostatic and anterior rectal wall temperatures were monitored for all treatments. Rectal wall temperatures were limited to 40 deg. C in 19 patients, 41 deg. C in 3 patients, and 42 deg. C in 8 patients. Logistic regression was used to estimate the log hazard of developing National Cancer Institute Common Toxicity Criteria Grade 2 toxicity based on temperature parameters. The following were calculated: hazard ratios, 95% confidence intervals, p values for statistical significance of each parameter, and proportion of variability explained for each parameter. Results: Gastrointestinal toxicity was limited to Grade 2. The rate of acute Grade 2 proctitis was greater for patients with an allowable rectal wall temperature of >40 deg. C. In this group, 7 of 11 patients experienced acute Grade 2 proctitis, as opposed to 3 of 19 patients in the group with rectal wall temperatures limited to 40 deg. C (p=0.004). Preliminary assessment of long-term toxicity revealed no differences in toxicity. Hazard ratios for acute Grade 2 proctitis for allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax were 9.33 (p=0.01), 3

  13. A multicentre randomised clinical trial of chemoradiotherapy plus hyperthermia versus chemoradiotherapy alone in patients with locally advanced cervical cancer

    Harima, Yoko; Ohguri, Takayuki; Imada, Hajime; Sakurai, Hideyuki; Ohno, Tatsuya; Hiraki, Yoshiyuki; Tuji, Koh; Tanaka, Masahiro; Terashima, Hiromi

    2016-01-01

    Purpose: To evaluate the effectiveness of whole-pelvic hyperthermia (HT) added to standard chemoradiotherapy (CRT) in locally advanced cervical cancer (CC), by investigating the clinical response and survival of patients treated with cisplatin-based CRT vs. CRT with HT (CRT + HT).Materials and methods: This study was conducted at five hospitals in Japan between September 2001 and March 2015 in patients with the International Federation of Gynecology and Obstetrics stage IB (bulky)–IVA CC unde...

  14. Study on the usefulness of high-frequency analysis of the combined treatment of cancer with hyperthermia

    Ji, Youn Sang; Dong, Kyung Rae; Yeo, Hwa Yeon

    2016-01-01

    In order to understand the usefulness to the high-frequency thermal therapy of cancer staging according to the TNM classification treatment, was to evaluate the effect of high frequency hyperthermia treatment approach through other means and whether other organs, according to the combined presence of transition. Targeted to receive more than a total of 1 cycle high frequency heat treatment at C hospital that performed the high-frequency hyperthermia cancer patients 92 people out stage, depending on the presence or absence of metastasis, combined hyperthermia patients for statistics before and after treatment the therapeutic effect of the therapeutic classification. Out of a total of 92 patients decrease 11 patients, stable 71 patients, with increase 10 patients, the rate of increase is the result of about 11% patients showed a decrease of about 89% is occupied by patients and a stable rate. There is strong evidence for the usefulness as a secondary therapy to maintain the quality of life, while slowing the progression of cancer by a high-frequency heat treatment

  15. Study on the usefulness of high-frequency analysis of the combined treatment of cancer with hyperthermia

    Ji, Youn Sang; Dong, Kyung Rae [Dept. of Radiological Technology, Gwangju Health University, Gwangju (Korea, Republic of); Yeo, Hwa Yeon [Dept. of of Radiology, Nambu University, Gwangju (Korea, Republic of)

    2016-11-15

    In order to understand the usefulness to the high-frequency thermal therapy of cancer staging according to the TNM classification treatment, was to evaluate the effect of high frequency hyperthermia treatment approach through other means and whether other organs, according to the combined presence of transition. Targeted to receive more than a total of 1 cycle high frequency heat treatment at C hospital that performed the high-frequency hyperthermia cancer patients 92 people out stage, depending on the presence or absence of metastasis, combined hyperthermia patients for statistics before and after treatment the therapeutic effect of the therapeutic classification. Out of a total of 92 patients decrease 11 patients, stable 71 patients, with increase 10 patients, the rate of increase is the result of about 11% patients showed a decrease of about 89% is occupied by patients and a stable rate. There is strong evidence for the usefulness as a secondary therapy to maintain the quality of life, while slowing the progression of cancer by a high-frequency heat treatment.

  16. Assessment of the efficacy of laser hyperthermia and nanoparticle-enhanced therapies by heat shock protein analysis

    Tang, Fei [Department of Precision Instrument, Tsinghua University, Beijing, 100084 (China); Zhang, Ye; Zhang, Juan; Liu, Ran, E-mail: liuran@tsinghua.edu.cn [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 100084 (China); Guo, Junwei [Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084 (China)

    2014-03-15

    Tumor thermotherapy is a method of cancer treatment wherein cancer cells are killed by exposing the body tissues to high temperatures. Successful clinical implementation of this method requires a clear understanding and assessment of the changes of the tumor area after the therapy. In this study, we evaluated the effect of near-infrared laser tumor thermotherapy at the molecular, cellular, and physical levels. We used single-walled carbon nanotubes (SWNTs) in combination with this thermotherapy. We established a mouse model for breast cancer and randomly divided the mice into four groups: mice with SWNT-assisted thermotherapy; mice heat treated without SWNT; mice injected with SWNTs without thermotherapy; and a control group. Tumors were irradiated using a near-infrared laser with their surface temperature remaining at approximately 45 °C. We monitored the tumor body growth trend closely by daily physical measurements, immunohistochemical staining, and H and E (hematoxylin-eosin) staining by stage. Our results showed that infrared laser hyperthermia had a significant inhibitory effect on the transplanted breast tumor, with an inhibition rate of 53.09%, and also significantly reduced the expression of the heat shock protein Hsp70. Furthermore, we have found that protein analysis and histological analysis can be used to assess therapeutic effects effectively, presenting broad application prospects for determining the effect of different treatments on tumors. Finally, we discuss the effects of SWNT-assisted near-infrared laser tumor thermotherapy on tumor growth at the molecular, cellular, and physical levels.

  17. MgFe{sub 2}O{sub 4}/ZrO{sub 2} composite nanoparticles for hyperthermia applications

    Rashid, Amin ur [Magnetism Laboratory, Department of Physics, COMSATS Institute of Information Technology, Islamabad (Pakistan); Department of Applied Physical and Material Sciences, University of Swat, Khyber Pakhtunkhwa (Pakistan); Humayun, Asif [Magnetism Laboratory, Department of Physics, COMSATS Institute of Information Technology, Islamabad (Pakistan); Manzoor, Sadia, E-mail: sadia_manzoor@comsats.edu.pk [Magnetism Laboratory, Department of Physics, COMSATS Institute of Information Technology, Islamabad (Pakistan)

    2017-04-15

    MgFe{sub 2}O{sub 4}/ZrO{sub 2} composites containing ZrO{sub 2} in different weight percentages from 0% to 80% were prepared via the citrate gel technique as potential candidate materials for magnetic hyperthermia. The biocompatible ceramic ZrO{sub 2} was introduced to prevent MgFe{sub 2}O{sub 4} nanoparticles from aggregation and to reduce their dipolar interactions in order to enhance the specific absorption rate (SAR). Structural and magnetic properties of the samples were studied using powder X-ray diffraction (XRD), transmission electron microscopy (TEM) and a vibrating sample magnetometer (VSM). Magnetically induced heating in radio frequency (RF) magnetic fields was observed in all samples. Most significantly, the sample with only 20 wt% MgFe{sub 2}O{sub 4} has been found to have a SAR that is larger than that of pure MgFe{sub 2}O{sub 4}. This is an important finding from the point of view of biomedical applications, because ZrO{sub 2} in known to have low toxicity and a higher biocompatibility as compared to ferrites. - Highlights: • MgFe{sub 2}O{sub 4} and ZrO{sub 2} composite nanoparticles with different weight percentages of ZrO{sub 2} were prepared via the citrate gel technique. • Significant variation in magnetic properties was observed with increasing the weight % of ZrO{sub 2}. • Magnetically induced heating was observed when the composites were subjected to RF magnetic field. • Most significantly, the sample 80 wt% ZrO{sub 2} has been found to have SAR that is larger than that of pure MgFe{sub 2}O{sub 4}. • The SAR was found to have a strong dependence on magnetic dipolar interactions.

  18. Magnetic nanoparticles for cancer therapy; Nanoparticulas magneticas para o tratamento do cancer

    Bakuzis, Andris F. [Universidade Federal de Goias (UFG), Goiania, GO (Brazil). Instituto de Fisica

    2014-07-01

    Full text: Magnetic nanoparticles have been used in several biomedical applications, spanning from cell separation, early diagnosis of metastasis to even the treatment of cancer via magnetic hyperthermia (MH). This last technique consists in the increase of temperature of nanoparticles when their magnetic moments interact with a magnetic alternating field. This effect has been suggested as an innovative therapy to cancer treatment, due to the delivery of heat or therapeutic agents, such as drugs, genes, and others. In addition, several clinical studies has demonstrated synergetic effects between hyperthermia and radiotherapy [1]. This indicates a great therapeutic potential for this noninvasive and targeted technique. In this talk we will discuss results from the literature and from our own group in the treatment of cancer via magnetic hyperthermia. Several types of magnetic nanoparticles suggested for this application will be discussed, as well as the historical evolution of this procedure, which although suggested in the late 50' only recently was approved in Europe for treatment of humans with brain tumors. (author) [Portuguese] Full text: Nanoparticulas magneticas tem sido utilizadas em diversas aplicacoes biomedicas, desde a separacao de celulas, marcacao de celulas-tronco, diagnostico precoce de metastases ao tratamento do cancer via hipertermia magnetica (HM). Esta ultima tecnica consiste no aumento da temperatura de nanoparticulas quando seus momentos magneticos interagem de forma adequada com um campo magnetico alternado. Este efeito tem sido idealizado como uma nova terapia para o tratamento do cancro, seja via entrega seletiva de calor ou mesmo pela liberacao de farmacos, genes ou outros agentes terapeuticos por meio desta acao externa. Adicionalmente, diversos estudos clinicos tem demonstrado efeitos sinergicos entre a hipertermia e tecnicas tradicionais de tratamento oncologico, como quimioterapia e radioterapia. Isto indica um forte potencial

  19. Field dependent transition to the non-linear regime in magnetic hyperthermia experiments: Comparison between maghemite, copper, zinc, nickel and cobalt ferrite nanoparticles of similar sizes

    E. L. Verde

    2012-09-01

    Full Text Available Further advances in magnetic hyperthermia might be limited by biological constraints, such as using sufficiently low frequencies and low field amplitudes to inhibit harmful eddy currents inside the patient's body. These incite the need to optimize the heating efficiency of the nanoparticles, referred to as the specific absorption rate (SAR. Among the several properties currently under research, one of particular importance is the transition from the linear to the non-linear regime that takes place as the field amplitude is increased, an aspect where the magnetic anisotropy is expected to play a fundamental role. In this paper we investigate the heating properties of cobalt ferrite and maghemite nanoparticles under the influence of a 500 kHz sinusoidal magnetic field with varying amplitude, up to 134 Oe. The particles were characterized by TEM, XRD, FMR and VSM, from which most relevant morphological, structural and magnetic properties were inferred. Both materials have similar size distributions and saturation magnetization, but strikingly different magnetic anisotropies. From magnetic hyperthermia experiments we found that, while at low fields maghemite is the best nanomaterial for hyperthermia applications, above a critical field, close to the transition from the linear to the non-linear regime, cobalt ferrite becomes more efficient. The results were also analyzed with respect to the energy conversion efficiency and compared with dynamic hysteresis simulations. Additional analysis with nickel, zinc and copper-ferrite nanoparticles of similar sizes confirmed the importance of the magnetic anisotropy and the damping factor. Further, the analysis of the characterization parameters suggested core-shell nanostructures, probably due to a surface passivation process during the nanoparticle synthesis. Finally, we discussed the effect of particle-particle interactions and its consequences, in particular regarding discrepancies between estimated

  20. Radiochemotherapy in combination with regional hyperthermia in preirradiated patients with recurrent rectal cancer

    Milani, V.; Issels, R.D.; Buecklein, V.; Institute of Molecular Immunology, Muenchen; Pazos, M.; Schaffer, P.; Wilkowski, R.; Duehmke, E.; Rahman, S.; Tschoep, K.; Schaffer, M.

    2008-01-01

    Background and Purpose: Encouraging results of phase II studies combining chemotherapy with radiotherapy have been published. In this study, the results of a multimodal salvage therapy including radiochemotherapy (RCT) and regional hyperthermia (RHT) in preirradiated patients with recurrent rectal cancer are reported. Patients and Methods: All patients enrolled had received previous pelvic irradiation (median dose 50.4 Gy). The median time interval between prior radiotherapy and the onset of local recurrence was 34 months. The combined treatment consisted of reirradiation with a median dose of 39.6 Gy (30.0-45.0 Gy), delivered in fractions of 1.8 Gy/day. 5-fluorouracil was given as continuous infusion 350 mg/m2/day five times weekly, and RHT (BSD-2000 system) was applied twice a week within 1 h after radiotherapy. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were overall survival, symptom control, and toxicity. Results: 24 patients (median age 59 years) with a previously irradiated locally recurrent adenocarcinoma of the rectum were enrolled. The median LPFS was 15 months (95% confidence interval 12-18 months) with a median follow-up of 27 months (16-37 months). The overall 1-year and 3-year survival rates were 87% and 30%, respectively. Pain was the main symptom in 17 patients. Release of pain was achieved in 12/17 patients (70%). No grade 3 or 4 hematologic or skin toxicity occurred. Grade 3 gastrointestinal acute toxicity was observed in 12.5% of the patients. Paratumoral thermometry revealed a homogeneous distribution of temperatures. Conclusion: RCT combined with RHT is an efficient salvage therapy showing high efficacy with acceptable toxicity and can be recommended as treatment option for this unfavorable group of preirradiated patients with local recurrence of rectal cancer. (orig.)

  1. Radiochemotherapy in combination with regional hyperthermia in preirradiated patients with recurrent rectal cancer

    Milani, V.; Issels, R.D.; Buecklein, V. [Ludwig-Maximilians-Univ., Muenchen (Germany). Univ. Hospital Grosshadern, Dept. of Internal Medicine III; Institute of Molecular Immunology, Muenchen (Germany). KKG Hyperthermie GSF-Haematologikum; Pazos, M.; Schaffer, P.; Wilkowski, R.; Duehmke, E. [Ludwig-Maximilians-Univ., Muenchen (Germany). Univ. Hospital Grosshadern, Dept. of Radiation Oncology; Rahman, S.; Tschoep, K.; Schaffer, M. [Ludwig-Maximilians-Univ., Muenchen (Germany). Univ. Hospital Grosshadern, Dept. of Internal Medicine III

    2008-03-15

    Background and Purpose: Encouraging results of phase II studies combining chemotherapy with radiotherapy have been published. In this study, the results of a multimodal salvage therapy including radiochemotherapy (RCT) and regional hyperthermia (RHT) in preirradiated patients with recurrent rectal cancer are reported. Patients and Methods: All patients enrolled had received previous pelvic irradiation (median dose 50.4 Gy). The median time interval between prior radiotherapy and the onset of local recurrence was 34 months. The combined treatment consisted of reirradiation with a median dose of 39.6 Gy (30.0-45.0 Gy), delivered in fractions of 1.8 Gy/day. 5-fluorouracil was given as continuous infusion 350 mg/m2/day five times weekly, and RHT (BSD-2000 system) was applied twice a week within 1 h after radiotherapy. The primary endpoint was local progression-free survival (LPFS); secondary endpoints were overall survival, symptom control, and toxicity. Results: 24 patients (median age 59 years) with a previously irradiated locally recurrent adenocarcinoma of the rectum were enrolled. The median LPFS was 15 months (95% confidence interval 12-18 months) with a median follow-up of 27 months (16-37 months). The overall 1-year and 3-year survival rates were 87% and 30%, respectively. Pain was the main symptom in 17 patients. Release of pain was achieved in 12/17 patients (70%). No grade 3 or 4 hematologic or skin toxicity occurred. Grade 3 gastrointestinal acute toxicity was observed in 12.5% of the patients. Paratumoral thermometry revealed a homogeneous distribution of temperatures. Conclusion: RCT combined with RHT is an efficient salvage therapy showing high efficacy with acceptable toxicity and can be recommended as treatment option for this unfavorable group of preirradiated patients with local recurrence of rectal cancer. (orig.)

  2. Chemo-radiotherapy plus hyperthermia in locally advanced cervical cancer: preliminary results of an institutional phase II study

    Gabbani, M.; Marciai, N.; Maluta, S.; Griso, C.; Merlin, F.; Cassandrini, P.; Giudici, S.; Franchi, M.; Zanini, L.

    2005-01-01

    Full text: Radiotherapy given concurrently with a cisplatin-based regimen has shown a benefit in patients with locally advanced cervical cancer so becoming the new standard treatment according to EBM criteria. Addition of hyperthermia to radiotherapy has also been proved to yield an advantage in survival and local control in pts affected by recurrent and local advanced cervical cancer in the Dutch Phase III trial so that the Consensus Forum of Kadota (Osaha June 2004) included cervical cancer among tumors treatable with hyperthermia. In our institutional multidisciplinary team a pilot study has been designed in order to evaluate feasibility, outcome and toxicity of tri-modality treatment in pts with locally advanced cervical cancer in our daily practice. Since January 2003 to now eight patients affected by cervical cancer with stage IB2 through IVA N0-N+ pelvic or paraaortic were entered the study. Six patients were treated at initial diagnosis and two patients after chemotherapy which had achieved stable disease. Treatment regimen consisted in 5 courses of weekly chemotherapy (cisplatin 40 mg/mq) with concurrent external radiotherapy to a total dose of 64-66 Gy on CTV1 and 45 Gy on para-aortic nodes plus boost in pts with enlarged nodes identified by imaging. Five weekly sessions of hyperthermia were performed by using BSD 2000 system and sigma 60 applicator. No significant toxicity occurred and all of the patients completed tri-modality treatment in accordance with the study protocol. Seven pts experienced a complete clinical remission and one patient a partial remission as defined by clinical and imaging examinations. After four months from the end of the treatment a patient with Stage IIB bulky tumor plus one pelvic positive node who was in complete remission (Clinical examination, MRI and TAC-PET three months from the end of the treatment were negative for evidence of disease) developed a bleeding recto-vaginal fistula plus central pelvic necrosis for which an

  3. Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study.

    Ranieri, Girolamo; Ferrari, Cristina; Di Palo, Alessandra; Marech, Ilaria; Porcelli, Mariangela; Falagario, Gianmarco; Ritrovato, Fabiana; Ramunni, Luigi; Fanelli, Margherita; Rubini, Giuseppe; Gadaleta, Cosmo Damiano

    2017-07-06

    As an angiogenesis inhibitor, bevacizumab has been investigated in combination with different chemotherapeutic agents, achieving an established role for metastatic cancer treatment. However, potential synergic anti-angiogenic effects of hyperthermia have not tested to date in literature. The aim of our study was to analyze efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia (HT) in metastatic cancer patients. Twenty-three patients with metastatic colorectal ( n = 16), ovarian ( n = 5), and breast ( n = 2) cancer were treated with HT in addition to a standard bevacizumab-based chemotherapy regimen. Treatment response assessment was performed, according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST), at 80 days (timepoint-1) and at 160 days (timepoint-2) after therapy. Disease Response Rate (DRR), considered as the proportion of patients who had the best response rating (complete response (CR), partial response (PR), or stable disease (SD)), was assessed at timepoint-1 and timepoint-2. Chi-squared for linear trend test was performed to evaluated the association between response groups (R/NR) and the number of previous treatment (none, 1, 2, 3), number of chemotherapy cycles (12), number of hyperthermia sessions (24), and lines of chemotherapy (I, II). Survival curves were estimated by Kaplan-Meier method. DRR was 85.7% and 72.2% at timepoint-1 and timepoint-2, respectively. HT was well tolerated without additional adverse effects on chemotherapy-related toxicity. Chi-squared for linear trend test demonstrated that the percentage of responders grew in relation to the number of chemotherapy cycles ( p = 0.015) and to number of HT sessions ( p chemotherapy cycles ( p chemotherapy with HT has a favorable tumor response, is feasible and well tolerated, and offers a potentially promising option for metastatic cancer patients.

  4. Gold Nanoparticle Mediated Phototherapy for Cancer

    Yao, C.; Zhang, L.; Wang, J.; He, Y.; Xin, J.; Wang, S.; Xu, H.; Zhang, Z.

    2016-01-01

    Gold nanoparticles exhibit very unique physiochemical and optical properties, which now are extensively studied in range of medical diagnostic and therapeutic applications. In particular, gold nanoparticles show promise in the advancement of cancer treatments. This review will provide insights into the four different cancer treatments such as photothermal therapy, gold nanoparticle-aided photodynamic therapy, gold nanoparticle-aided radiation therapy, and their use as drug carrier. We also discuss the mechanism of every method and the adverse effects and its limitations

  5. Folic acid-conjugated Fe{sub 3}O{sub 4} magnetic nanoparticles for hyperthermia and MRI in vitro and in vivo

    Jiang, Q.L.; Zheng, S.W. [College of Chemistry, Chemical Engineering and Materials Science and Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China); Hong, R.Y., E-mail: rhong@suda.edu.cn [College of Chemistry, Chemical Engineering and Materials Science and Key Laboratory of Organic Synthesis of Jiangsu Province, Soochow University, SIP, Suzhou 215123 (China); College of Chemistry and Chemical Engineering, Fuzhou University, Fuzhou 350002 (China); Deng, S.M.; Guo, L. [The First Affiliated Hospital of Soochow University, Suzhou 215011 (China); Hu, R.L. [Department of Thoracic Surgery, Hangzhou First People' s Hospital, Hangzhou 310006 (China); Gao, B.; Huang, M.; Cheng, L.F. [College of Medicine, Soochow University, SIP, Suzhou 215123 (China); Liu, G.H. [Respiration Department, Suzhou Municipal Hospital (East-Section), Suzhou 215001 (China); Wang, Y.Q. [Key Laboratory of Environmental Materials and Engineering of Jiangsu Province, Yangzhou University, Yangzhou 225002 (China)

    2014-07-01

    The folic acid (FA)-conjugated Fe{sub 3}O{sub 4} magnetic nanoparticles (MNPs) were synthesized by co-precipitation of Fe{sup 3+} and Fe{sup 2+} solution followed by surface modification with carboxymethyl dextran (CMD) to form carboxymethyl group terminated MNPs, then FA was conjugated with the carboxyl group functionalized MNPs. The morphology and properties of obtained nanoparticles were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), UV–visible spectra (UV–vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), vibrating sample magnetometer (VSM) and thermogravimetric analysis (TGA). The FA-conjugated MNPs exhibited relatively high saturation magnetization and fast magneto-temperature response which could be applied to hyperthermia therapy. To determine the accurate targeting effect of FA, we chose FA-conjugated MNPs as MRI contrast enhancement agent for detection of KB cells with folate receptor over-expression in vitro and in vivo. The results show that these magnetic nanoparticles appear to be the promising materials for local hyperthermia and MRI.

  6. Magnetic nanoparticles for application in cancer therapy

    Rivas, J. [Department of Applied Physics, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Banobre-Lopez, M. [Department of Physical Chemistry, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Pineiro-Redondo, Y. [Department of Applied Physics, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Rivas, B., E-mail: jose.rivas@usc.es [Department of Operative Dentistry and Endodontics, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Lopez-Quintela, M.A. [Department of Physical Chemistry, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain)

    2012-10-15

    Magnetic particles play nowadays an important role in different technological areas with potential applications in fields such as electronics, energy and biomedicine. In this report we will focus on the hyperthermia properties of magnetite nanoparticles and the effect of several chemical/physical parameters on their heating properties. We will discuss about the need of searching new smaller magnetic systems in order to fulfill the required physical properties which allow treating tumoral tissues more efficiently by means of magnetically induced heat. Preliminary results will be shown about the effect of a biocompatible shell of core-shell magnetite NPs on the heating properties by application of a RF magnetic field.

  7. Water-dispersible sugar-coated iron oxide nanoparticles. An evaluation of their relaxometric and magnetic hyperthermia properties.

    Lartigue, Lenaic; Innocenti, Claudia; Kalaivani, Thangavel; Awwad, Azzam; Sanchez Duque, Maria del Mar; Guari, Yannick; Larionova, Joulia; Guérin, Christian; Montero, Jean-Louis Georges; Barragan-Montero, Véronique; Arosio, Paolo; Lascialfari, Alessandro; Gatteschi, Dante; Sangregorio, Claudio

    2011-07-13

    Synthesis of functionalized magnetic nanoparticles (NPs) for biomedical applications represents a current challenge. In this paper we present the synthesis and characterization of water-dispersible sugar-coated iron oxide NPs specifically designed as magnetic fluid hyperthermia heat mediators and negative contrast agents for magnetic resonance imaging. In particular, the influence of the inorganic core size was investigated. To this end, iron oxide NPs with average size in the range of 4-35 nm were prepared by thermal decomposition of molecular precursors and then coated with organic ligands bearing a phosphonate group on one side and rhamnose, mannose, or ribose moieties on the other side. In this way a strong anchorage of the organic ligand on the inorganic surface was simply realized by ligand exchange, due to covalent bonding between the Fe(3+) atom and the phosphonate group. These synthesized nanoobjects can be fully dispersed in water forming colloids that are stable over very long periods. Mannose, ribose, and rhamnose were chosen to test the versatility of the method and also because these carbohydrates, in particular rhamnose, which is a substrate of skin lectin, confer targeting properties to the nanosystems. The magnetic, hyperthermal, and relaxometric properties of all the synthesized samples were investigated. Iron oxide NPs of ca. 16-18 nm were found to represent an efficient bifunctional targeting system for theranostic applications, as they have very good transverse relaxivity (three times larger than the best currently available commercial products) and large heat release upon application of radio frequency (RF) electromagnetic radiation with amplitude and frequency close to the human tolerance limit. The results have been rationalized on the basis of the magnetic properties of the investigated samples.

  8. On the temperature control in self-controlling hyperthermia therapy

    Ebrahimi, Mahyar, E-mail: ebrahimi_m@mehr.sharif.ir

    2016-10-15

    In self-controlling hyperthermia therapy, once the desired temperature is reached, the heat generation ceases and overheating is prevented. In order to design a system that generates sufficient heat without thermal ablation of surrounding healthy tissue, a good understanding of temperature distribution and its change with time is imperative. This study is conducted to extend our understanding about the heat generation and transfer, temperature distribution and temperature rise pattern in the tumor and surrounding tissue during self-controlling magnetic hyperthermia. A model consisting of two concentric spheres that represents the tumor and its surrounding tissue is considered and temperature change pattern and temperature distribution in tumor and surrounding tissue are studied. After describing the model and its governing equations and constants precisely, a typical numerical solution of the model is presented. Then it is showed that how different parameters like Curie temperature of nanoparticles, magnetic field amplitude and nanoparticles concentration can affect the temperature change pattern during self-controlling magnetic hyperthermia. The model system herein discussed can be useful to gain insight on the self-controlling magnetic hyperthermia while applied to cancer treatment in real scenario and can be useful for treatment strategy determination. - Highlights: • Temperature change pattern in tumor and surrounding tissue are studied. • The model system herein can be useful for treatment strategy determination. • In the work described herein, emphasis is on the effect of low Curie temperature. • If the equilibrium temperature can be tuned appropriately, the stay time will be infinite.

  9. On the temperature control in self-controlling hyperthermia therapy

    Ebrahimi, Mahyar

    2016-01-01

    In self-controlling hyperthermia therapy, once the desired temperature is reached, the heat generation ceases and overheating is prevented. In order to design a system that generates sufficient heat without thermal ablation of surrounding healthy tissue, a good understanding of temperature distribution and its change with time is imperative. This study is conducted to extend our understanding about the heat generation and transfer, temperature distribution and temperature rise pattern in the tumor and surrounding tissue during self-controlling magnetic hyperthermia. A model consisting of two concentric spheres that represents the tumor and its surrounding tissue is considered and temperature change pattern and temperature distribution in tumor and surrounding tissue are studied. After describing the model and its governing equations and constants precisely, a typical numerical solution of the model is presented. Then it is showed that how different parameters like Curie temperature of nanoparticles, magnetic field amplitude and nanoparticles concentration can affect the temperature change pattern during self-controlling magnetic hyperthermia. The model system herein discussed can be useful to gain insight on the self-controlling magnetic hyperthermia while applied to cancer treatment in real scenario and can be useful for treatment strategy determination. - Highlights: • Temperature change pattern in tumor and surrounding tissue are studied. • The model system herein can be useful for treatment strategy determination. • In the work described herein, emphasis is on the effect of low Curie temperature. • If the equilibrium temperature can be tuned appropriately, the stay time will be infinite.

  10. Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials

    Vernon, Clare C.; Hand, Jeffrey W.; Field, Stanley B.; Machin, David; Whaley, Jill B.; Zee, Jacoba van der; Putten, Wim L.J. van; Rhoon, Gerard C. van; Dijk, Jan D.P. van; Gonzalez, Dionisio Gonzalez; Liu, F.-F.; Goodman, Phyllis; Sherar, Michael

    1996-01-01

    Purpose: Claims for the value of hyperthermia as an adjunct to radiotherapy in the treatment of cancer have mostly been based on small Phase I or II trials. To test the benefit of this form of treatment, randomized Phase III trials were needed. Methods and Materials: Five randomized trials addressing this question were started between 1988 and 1991. In these trials, patients were eligible if they had advanced primary or recurrent breast cancer, and local radiotherapy was indicated in preference to surgery. In addition, heating of the lesions and treatment with a prescribed (re)irradiation schedule had to be feasible and informed consent was obtained. The primary endpoint of all trials was local complete response. Slow recruitment led to a decision to collaborate and combine the trial results in one analysis, and report them simultaneously in one publication. Interim analyses were carried out and the trials were closed to recruitment when a previously agreed statistically significant difference in complete response rate was observed in the two larger trials. Results: We report on pretreatment characteristics, the treatments received, the local response observed, duration of response, time to local failure, distant progression and survival, and treatment toxicity of the 306 patients randomized. The overall CR rate for RT alone was 41% and for the combined treatment arm was 59%, giving, after stratification by trial, an odds ratio of 2.3. Not all trials demonstrated an advantage for the combined treatment, although the 95% confidence intervals of the different trials all contain the pooled odds ratio. The greatest effect was observed in patients with recurrent lesions in previously irradiated areas, where further irradiation was limited to low doses. Conclusion: The combined result of the five trials has demonstrated the efficacy of hyperthermia as an adjunct to radiotherapy for treatment of recurrent breast cancer. The implication of these encouraging results is that

  11. Rib fractures after reirradiation plus hyperthermia for recurrent breast cancer. Predictive factors

    Oldenborg, Sabine; Valk, Christel; Os, Rob van; Voerde Sive Voerding, Paul zum; Crezee, Hans; Tienhoven, Geertjan van; Rasch, Coen [University of Amsterdam, Department of Radiation Oncology, Z1-215, Academic Medical Center, Amsterdam (Netherlands); Oei, Bing; Venselaar, Jack [Institute Verbeeten (BVI), Tilburg (Netherlands); Randen, Adrienne van [University of Amsterdam (AMC), Department of Radiology Academic Medical Center, Amsterdam (Netherlands)

    2016-04-15

    Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors on the occurrence of rib fractures. From 1982-2005, 234 patients were treated with adjuvant reRT + HT after surgery for LR. ReRT consisted typically of 8 fractions of 4 Gy twice a week, or 12 fractions of 3 Gy four times a week. A total of 118 patients were irradiated with abutted photon and electron fields. In all, 60 patients were irradiated using either one or alternating combinations of abutted AP electron fields. Hyperthermia was given once or twice a week. The 5-year infield local control (LC) rate was 70 %. Rib fractures were detected in 16 of 234 patients (actuarial risk: 7 % at 5 years). All rib fractures occurred in patients treated with a combination of photon and abutted electron fields (p = 0.000); in 15 of 16 patients fractures were located in the abutment regions. The other significant predictive factors for rib fractures were a higher fraction dose (p = 0.040), large RT fields, and treatment before the year 2000. ReRT + HT results in long-term LC. The majority of rib fractures were located in the photon/electron abutment area, emphasizing the disadvantage of field overlap. Large abutted photon/electron fields combined with 4 Gy fractions increase the number of rib fractures in this study group. However, as these factors were highly correlated no relative importance of the individual factors could be estimated. Increasing the number of HT sessions a week does not increase the risk of rib fractures. (orig.) [German] Der kombinierte Einsatz von Rebestrahlung (reRT) und Hyperthermie (HT) zeigt eine hohe Wirksamkeit bei Patienten mit lokoregional rezidiviertem Brustkrebs (LR). Jedoch koennen zusaetzliche toxische Effekte von reRT (z. B. Rippenfrakturen

  12. 500 kHZ intracavitary hyperthermia in the treatment of patients with cervical and endometrial cancer - preliminary results and treatment description

    Piotrowicz, N.; Lyczek, J.; Zielinski, J.; Debicki, P.

    2002-01-01

    The effectiveness of elevated temperature (hyperthermia) in cancer treatment is a well-known issue. However, due to technical problems with generating hyperthermia within the tumour and, at the same time, sparing the healthy tissues, in practice this modality is not widely used. Local hyperthermia was induced by a computer-controlled generator (500 kHz) with three amplifiers transmitting energy to the lesion via a modified uterine brachytherapy applicator. Temperature was measured with 3 thermocouples.Total treatment time was 60-90 minutes. 10 patients with cervical and endometrial cancer were enrolled into this study and 11 procedures were performed. Prior to hyperthermia all patients were treated with external field irradiation to the pelvis to the dose of 45-46 Gy. Intracavitary LDR/HDR brachytherapy (dose of 45 Gy/point Ai n two fractions) with colpostat used for the hyperthermia procedure was than performed. In all cases, except one, caused by equipment failure, biologically stable temperature was observed. No severe side effects of treatment were observed. There was no need to terminate treatment due to high temperature intolerance. (author)

  13. Study of the therapeutic effect of 188Re labeled folate targeting albumin nanoparticle coupled with cis-diamminedichloroplatinum cisplatin on human ovarian cancer.

    Tang, Qiusha; Chen, Daozhen

    2014-01-01

    This paper aimed to investigate the treatment efficiency of 188Re labeled folate targeting albumin nanoparticles with cis-Diamminedichloroplatinum Cisplatin (188Re-folate-CDDP/HAS MNP) on human ovarian cancer. SKOV3 cells or tumor-bearing mice were divided into different groups and treated as follow: (A) negative control; (B) chemotherapy; (C) radiotherapy; (D) hyperthermia; (E) chemotherapy and radiotherapy; (F) chemotherapy and hyperthermia; (G) radiotherapy and hyperthermia; (H) chemotherapy, radiotherapy and hyperthermia. Treatment of B to H inhibited proliferation of SKOV3 cells, with the greatest inhibition being observed in group H (P<0.05). Obvious apoptotic hypodiploid peak appeared beside G1 phase in groups of B to H. The apoptotic rates of SKOV3 cells in groups of A to H were 0.08%, 7.56%, 8.64%, 17.14%, 21.64%, 23.77%, 33.94% and 57.16%, respectively. Our findings in vivo study showed that the mass of tumor in each group of B to H was significantly lower than that in the negative control (p <0.05). In addition, compared with each group of B to G, group H showed highest inhibition of tumor growth (p<0.05). In conclusion, the combination of magnetic induced hyperthermia, chemotherapy and targeted radionuclide of radiation exposure can effectively inhibit the growth of ovarian cancer, which indicates a potential applications in ovarian cancer treatment.

  14. A randomized clinical trial of hyperthermia and radiation versus radiation alone for superficially located cancers

    Egawa, Sunao; Tsukiyama, Iwao; Watanabe, Shaw

    1989-01-01

    A randomized clinical trial was performed in order to evaluate the effect of combined hyperthermia and radiation for superficially located tumors. Ten institutions participated in this study and 92 evaluable patients were entered from September 1985 to March 1987 (44 patients for radiation plus hyperthermia and 48 for radiation only). Superficially located tumors, more than 3x3 cm in diameter, regardless of whether they were primary or metastatic, and of their histology, were included in the study. Radiotherapy was performed by the conventional fractionation method (2 Gyx5/week). Hyperthermia was conducted once a week. There was no statistical difference between the two groups regarding age, sex, the distribution of tumors and treatment parameters. The complete response (CR) and partial response (PR) rate for the hyperthermia plus radiation group was 81.8%, while the rate for the radiation alone group was 62.6% (p<0.05). Six factors were selected for analysis of the above effect by a multiple logistic model. Sex contributed the most (p=0.001), then the site of the tumor (p=0.016) and the method of treatment (p=0.023). Sex and the site influenced the results. Age, irradiation dose and frequency and duration of heating were not significant factors for response to treatment. (author)

  15. The magnetic and hyperthermia studies of bare and silica-coated La.sub.0.75./sub.Sr.sub.0.25./sub.MnO.sub.3./sub. nanoparticles

    Kaman, Ondřej; Veverka, Pavel; Jirák, Zdeněk; Maryško, Miroslav; Knížek, Karel; Veverka, Miroslav; Kašpar, P.; Burian, M.; Šepelák, V.; Pollert, Emil

    2011-01-01

    Roč. 13, č. 3 (2011), s. 1237-1252 ISSN 1388-0764 R&D Projects: GA AV ČR KAN200200651 Institutional research plan: CEZ:AV0Z10100521 Keywords : perovskite manganite * magnetic nanoparticles * hyperthermia * size distribution * synthesis * nanomedicine Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.287, year: 2011

  16. Implant strategies for endocervical and interstitial ultrasound hyperthermia adjunct to HDR brachytherapy for the treatment of cervical cancer

    Wootton, Jeffery H.; Prakash, Punit; Hsu, I.-Chow Joe; Diederich, Chris J.

    2011-07-01

    Catheter-based ultrasound devices provide a method to deliver 3D conformable heating integrated with HDR brachytherapy delivery. Theoretical characterization of heating patterns was performed to identify implant strategies for these devices which can best be used to apply hyperthermia to cervical cancer. A constrained optimization-based hyperthermia treatment planning platform was used for the analysis. The proportion of tissue >=41 °C in a hyperthermia treatment volume was maximized with constraints Tmax 200 cm3) is possible using multiple sectored interstitial and endocervical ultrasound devices. The endocervical device can heat >41 °C to 4.6 cm diameter compared to 3.6 cm for the interstitial. Sectored applicators afford tight control of heating that is robust to perfusion changes in most regularly spaced configurations. T90 in example patient cases was 40.5-42.7 °C (1.9-39.6 EM43 °C) at 1 kg m-3 s-1 with 10/14 patients >=41 °C. Guidelines are presented for positioning of implant catheters during the initial surgery, selection of ultrasound applicator configurations, and tailored power schemes for achieving T90 >= 41 °C in clinically practical implant configurations. Catheter-based ultrasound devices, when adhering to the guidelines, show potential to generate conformal therapeutic heating ranging from a single endocervical device targeting small volumes local to the cervix (directional interstitial applicators in the lateral periphery to target much larger volumes (6 cm radial), while preferentially limiting heating of the bladder and rectum.

  17. A Reconstruction Method for the Estimation of Temperatures of Multiple Sources Applied for Nanoparticle-Mediated Hyperthermia

    Idan Steinberg

    2018-03-01

    Full Text Available Solid malignant tumors are one of the leading causes of death worldwide. Many times complete removal is not possible and alternative methods such as focused hyperthermia are used. Precise control of the hyperthermia process is imperative for the successful application of such treatment. To that end, this research presents a fast method that enables the estimation of deep tissue heat distribution by capturing and processing the transient temperature at the boundary based on a bio-heat transfer model. The theoretical model is rigorously developed and thoroughly validated by a series of experiments. A 10-fold improvement is demonstrated in resolution and visibility on tissue mimicking phantoms. The inverse problem is demonstrated as well with a successful application of the model for imaging deep-tissue embedded heat sources. Thereby, allowing the physician then ability to dynamically evaluate the hyperthermia treatment efficiency in real time.

  18. A Reconstruction Method for the Estimation of Temperatures of Multiple Sources Applied for Nanoparticle-Mediated Hyperthermia.

    Steinberg, Idan; Tamir, Gil; Gannot, Israel

    2018-03-16

    Solid malignant tumors are one of the leading causes of death worldwide. Many times complete removal is not possible and alternative methods such as focused hyperthermia are used. Precise control of the hyperthermia process is imperative for the successful application of such treatment. To that end, this research presents a fast method that enables the estimation of deep tissue heat distribution by capturing and processing the transient temperature at the boundary based on a bio-heat transfer model. The theoretical model is rigorously developed and thoroughly validated by a series of experiments. A 10-fold improvement is demonstrated in resolution and visibility on tissue mimicking phantoms. The inverse problem is demonstrated as well with a successful application of the model for imaging deep-tissue embedded heat sources. Thereby, allowing the physician then ability to dynamically evaluate the hyperthermia treatment efficiency in real time.

  19. Implant strategies for endocervical and interstitial ultrasound hyperthermia adjunct to HDR brachytherapy for the treatment of cervical cancer

    Wootton, Jeffery H; Prakash, Punit; Hsu, I-Chow Joe; Diederich, Chris J

    2011-01-01

    Catheter-based ultrasound devices provide a method to deliver 3D conformable heating integrated with HDR brachytherapy delivery. Theoretical characterization of heating patterns was performed to identify implant strategies for these devices which can best be used to apply hyperthermia to cervical cancer. A constrained optimization-based hyperthermia treatment planning platform was used for the analysis. The proportion of tissue ≥41 deg. C in a hyperthermia treatment volume was maximized with constraints T max ≤ 47 deg. C, T rectum ≤ 41.5 deg. C, and T bladder ≤ 42.5 deg. C. Hyperthermia treatment was modeled for generalized implant configurations and complex configurations from a database of patients (n = 14) treated with HDR brachytherapy. Various combinations of endocervical (360 0 or 2 x 180 0 output; 6 mm OD) and interstitial (180 0 , 270 0 , or 360 0 output; 2.4 mm OD) applicators within catheter locations from brachytherapy implants were modeled, with perfusion constant (1 or 3 kg m -3 s -1 ) or varying with location or temperature. Device positioning, sectoring, active length and aiming were empirically optimized to maximize thermal coverage. Conformable heating of appreciable volumes (>200 cm 3 ) is possible using multiple sectored interstitial and endocervical ultrasound devices. The endocervical device can heat >41 deg. C to 4.6 cm diameter compared to 3.6 cm for the interstitial. Sectored applicators afford tight control of heating that is robust to perfusion changes in most regularly spaced configurations. T 90 in example patient cases was 40.5-42.7 deg. C (1.9-39.6 EM 43deg.C ) at 1 kg m -3 s -1 with 10/14 patients ≥41 deg. C. Guidelines are presented for positioning of implant catheters during the initial surgery, selection of ultrasound applicator configurations, and tailored power schemes for achieving T 90 ≥ 41 deg. C in clinically practical implant configurations. Catheter-based ultrasound devices, when adhering to the guidelines, show

  20. Ultrasound guided pO2 measurement of breast cancer reoxygenation after neoadjuvant chemotherapy and hyperthermia treatment.

    Vujaskovic, Z; Rosen, E L; Blackwell, K L; Jones, E L; Brizel, D M; Prosnitz, L R; Samulski, T V; Dewhirst, M W

    2003-01-01

    The objective of this study was to determine whether neoadjuvant chemotherapy in combination with hyperthermia (HT) would improve oxygenation in locally advanced breast tumours. The study describes a new optimized ultrasound guided technique of pO2 measurement using Eppendorf polarographic oxygen probes in 18 stage IIB-III breast cancer patients. Prior to treatment, tumour hypoxia (median pO2pO2=3.2 mmHg). Seven patients had well oxygenated tumours (median pO2 of 48.3 mmHg). Eight patients with hypoxic tumours prior to treatment had a significant improvement (p=0.0008) in tumour pO2 after treatment (pO2 increased to 19.2 mmHg). In three patients, tumours remained hypoxic (average median pO2=4.5 mmHg). The advantages of the ultrasound guided pO2 probe are in the accuracy of the Eppendorf electrode placement in tumour tissue, the ability to monitor electrode movement through the tumour tissue during the measurement and the ability to avoid electrode placement near or in large blood vessels by using colour Doppler imaging. The results of this preliminary study suggest that the combination of neoadjuvant chemotherapy and hyperthermia improves oxygenation in locally advanced breast tumours that are initially hypoxic.

  1. Experimental ex-vivo validation of PMMA-based bone cements loaded with magnetic nanoparticles enabling hyperthermia of metastatic bone tumors

    Mariem Harabech

    2017-05-01

    Full Text Available Percutaneous vertebroplasty comprises the injection of Polymethylmethacrylate (PMMA bone cement into vertebrae and can be used for the treatment of compression fractures of vertebrae. Metastatic bone tumors can cause such compression fractures but are not treated when injecting PMMA-based bone cement. Hyperthermia of tumors can on the other hand be attained by placing magnetic nanoparticles (MNPs in an alternating magnetic field (AMF. Loading the PMMA-based bone cement with MNPs could both serve vertebra stabilization and metastatic bone tumor hyperthermia when subjecting this PMMA-MNP to an AMF. A dedicated pancake coil is designed with a self-inductance of 10 μH in series with a capacitance of 0.1 μF that acts as resonant inductor-capacitor circuit to generate the AMF. The thermal rise is appraised in beef vertebra placed at 10 cm from the AMF generating circuit using optical temperatures sensors, i.e. in the center of the PMMA-MNP bone cement, which is located in the vicinity of metastatic bone tumors in clinical applications; and in the spine, which needs to be safeguarded to high temperature exposures. Results show a temperature rise of about 7 °C in PMMA-MNP whereas the temperature rise in the spine remains limited to 1 °C. Moreover, multicycles heating of PMMA-MNP is experimentally verified, validating the technical feasibility of having PMMA-MNP as basic component for percutaneous vertebroplasty combined with hyperthermia treatment of metastatic bone tumors.

  2. Zinc substituted ferrite nanoparticles with Zn{sub 0.9}Fe{sub 2.1}O{sub 4} formula used as heating agents for in vitro hyperthermia assay on glioma cells

    Hanini, Amel [Interface Traitement Organisation et Dynamique des Systèmes (TODYS), Université Paris Diderot, Sorbonne Paris Cité, CNRS UMR-7086, 75013, Paris (France); Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS UMR-8104, INSERM U1016, 75005 Paris (France); Laboratoire de Physiologie Intégrée (LPI), Université de Carthage, 7021, Jarzouna (Tunisia); Lartigue, Lenaic [Matière et Systèmes Complexes (MSC), Université Paris Diderot, Sorbonne Paris Cité, CNRS UMR-7057, 75013, Paris (France); Gavard, Julie [Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS UMR-8104, INSERM U1016, 75005 Paris (France); Kacem, Kamel [Laboratoire de Physiologie Intégrée (LPI), Université de Carthage, 7021, Jarzouna (Tunisia); Wilhelm, Claire; Gazeau, Florence [Matière et Systèmes Complexes (MSC), Université Paris Diderot, Sorbonne Paris Cité, CNRS UMR-7057, 75013, Paris (France); Chau, François [Interface Traitement Organisation et Dynamique des Systèmes (TODYS), Université Paris Diderot, Sorbonne Paris Cité, CNRS UMR-7086, 75013, Paris (France); and others

    2016-10-15

    In this paper we investigate the ability of zinc rich ferrite nanoparticles to induce hyperthermia on cancer cells using an alternating magnetic field (AMF). First, we synthesized ferrites and then we analyzed their physico-chemical properties by transmission electron microscopy, X-ray diffraction and magnetic and magnetocalorimetric measurements. We found that the polyol-made magnetically diluted particles are of 11 nm in size. They are superparamagnetic at body temperature (310 K) with a low but non-negligible magnetization. Interestingly, as nano-ferrimagnets they exhibit a Curie temperature of 366 K, close to the therapeutic temperature range. Their effect on human healthy endothelial (HUVEC) and malignant glioma (U87-MG) cells was also evaluated using MTT viability assays. Incubated with the two cell lines, at doses ≤100 µg mL{sup −1} and contact times ≤4 h, they exhibit a mild in vitro toxicity. In these same operating biological conditions and coupled to AMF (700 kHz and 34.4 Oe) for 1 h, they rapidly induce a net temperature increase. In the case of tumor cells it reaches 4 K, making the produced particles particularly promising for self-regulated magnetically-induced heating in local glioma therapy. - Highlights: • Highly crystallized monodisperse 11 nm sized Zn{sub 0.9}Fe{sub 2.1}O{sub 4} particles were produced in polyol. • They exhibit a superparamagnetic behavior at 37 °C with a magnetization of 12 emu g{sup −1} at 50 kOe. • Their Curie temperature reaches 88 °C, close to the therapeutic hyperthermia temperatures. • Incubated with glioma cells and exposed to ac-magnetic field they induce a 4 °C temperature increase. • They can be considered as potential self-regulated heating probes for glioma therapy.

  3. Folate attached, curcumin loaded Fe_3O_4 nanoparticles: A novel multifunctional drug delivery system for cancer treatment

    Thu Huong, Le Thi; Nam, Nguyen Hoai; Doan, Do Hai; My Nhung, Hoang Thi; Quang, Bui Thuc; Nam, Pham Hong; Thong, Phan Quoc; Phuc, Nguyen Xuan; Thu, Ha Phuong

    2016-01-01

    Study and development of drug delivery nanosystem for cancer treatment are attracting great attention in recent years. In this work, we studied the role of folic acid as a targeting factor on magnetic nanoparticle Fe_3O_4 based curcumin loading nanosystem. Characteristics of the nanosystems were investigated by Fourier transform infrared spectroscopy (FTIR) and field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), thermal gravimetric analysis (TGA) and vibrating sample magnetometer (VSM), while targeting role of folic was accessed in vivo on tumor bearing mice. The results showed that folate attached Fe_3O_4 based curcumin loading nanosystem has very small size and exhibits better targeting effect compared to the counterpart without folate. In addition, magnetic induction heating of this nanosystem evidenced its potential for cancer hyperthermia. - Highlights: • Folate attached, curcumin loaded Fe3O4 nanoparticles were prepared and characterized. • The NPs have high curcumin loading capacity and good ability for hyperthermia. • Folate shows its bioactivity of effectively targeting the NPs to tumor tissues. • Chemotherapy, hyperthermia and targeting factor are all well combined in the NPs.

  4. A Nanotechnology-based Strategy to Increase the Efficiency of Cancer Diagnosis and Therapy: Folate-conjugated Gold Nanoparticles.

    Beik, Jaber; Khademi, Sara; Attaran, Neda; Sarkar, Saeed; Shakeri-Zadeh, Ali; Ghaznavi, Habib; Ghadiri, Hossein

    2017-01-01

    Gold nanoparticles (AuNPs), owing to their elegant physicochemical properties, have recently been introduced as promising theranostic nanoparticles. Folic acid is a necessary vitamin for cell proliferation. Accordingly, the surface functionalization of AuNP with folic acid may offer a great potential for the development of a strategy to increase the efficiency of cancer diagnosis and therapy based on the new nanotechnology. In this study, we have reviewed the recent progress made in the design and the biomedical application of various folate-conjugated gold nanoparticles (FAuNPs). We performed a structured search in bibliographic databases and made a comprehensive list of relevant papers. The main subjects considered in this review included (1) methods for the preparation of F-AuNPs, (2) applications of F-AuNPs in computed tomography (CT), and (3) the use of F-AuNPs in targeted cancer therapy. As many as 96 papers were selected for the review. Accordingly, we explained the noncovalent and the covalent methods of fabricating the various types of F-AuNPs. Particular applications of F-AuNP in cancer diagnosis using the CT scan modality were described. In addition, the applications of F-AuNPs in targeted radiation therapy, chemotherapy, and hyperthermia were elucidated in depth. In the hyperthermia section, we presented certain extra explanations on F-AuNP-based laser, radiofrequency, and ultrasoundbased hyperthermia methods. This review identifies the important roles of F-AuNPs in current cancer studies that are being undertaken worldwide. The findings of this review confirm that F-AuNP is a new theranostic agent, which has a great potential for simultaneous cancer therapy and diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Non-Invasive Radiofrequency-Induced Targeted Hyperthermia for the Treatment of Hepatocellular Carcinoma

    Mustafa Raoof

    2011-01-01

    Full Text Available Targeted biological therapies for hepatocellular cancer have shown minimal improvements in median survival. Multiple pathways to oncogenesis leading to rapid development of resistance to such therapies is a concern. Non-invasive radiofrequency field-induced targeted hyperthermia using nanoparticles is a radical departure from conventional modalities. In this paper we underscore the need for innovative strategies for the treatment of hepatocellular cancer, describe the central paradigm of targeted hyperthermia using non-invasive electromagnetic energy, review the process of characterization and modification of nanoparticles for the task, and summarize data from cell-based and animal-based models of hepatocellular cancer treated with non-invasive RF energy. Finally, future strategies and challenges in bringing this modality from bench to clinic are discussed.

  6. Magnetic hyperthermia properties of nanoparticles inside lysosomes using kinetic Monte Carlo simulations: Influence of key parameters and dipolar interactions, and evidence for strong spatial variation of heating power

    Tan, R. P.; Carrey, J.; Respaud, M.

    2014-12-01

    Understanding the influence of dipolar interactions in magnetic hyperthermia experiments is of crucial importance for fine optimization of nanoparticle (NP) heating power. In this study we use a kinetic Monte Carlo algorithm to calculate hysteresis loops that correctly account for both time and temperature. This algorithm is shown to correctly reproduce the high-frequency hysteresis loop of both superparamagnetic and ferromagnetic NPs without any ad hoc or artificial parameters. The algorithm is easily parallelizable with a good speed-up behavior, which considerably decreases the calculation time on several processors and enables the study of assemblies of several thousands of NPs. The specific absorption rate (SAR) of magnetic NPs dispersed inside spherical lysosomes is studied as a function of several key parameters: volume concentration, applied magnetic field, lysosome size, NP diameter, and anisotropy. The influence of these parameters is illustrated and comprehensively explained. In summary, magnetic interactions increase the coercive field, saturation field, and hysteresis area of major loops. However, for small amplitude magnetic fields such as those used in magnetic hyperthermia, the heating power as a function of concentration can increase, decrease, or display a bell shape, depending on the relationship between the applied magnetic field and the coercive/saturation fields of the NPs. The hysteresis area is found to be well correlated with the parallel or antiparallel nature of the dipolar field acting on each particle. The heating power of a given NP is strongly influenced by a local concentration involving approximately 20 neighbors. Because this local concentration strongly decreases upon approaching the surface, the heating power increases or decreases in the vicinity of the lysosome membrane. The amplitude of variation reaches more than one order of magnitude in certain conditions. This transition occurs on a thickness corresponding to approximately

  7. Investigation of magnetic properties of Fe{sub 3}O{sub 4} nanoparticles using temperature dependent magnetic hyperthermia in ferrofluids

    Nemala, H.; Thakur, J. S.; Lawes, G.; Naik, R., E-mail: rnaik@wayne.edu [Department of Physics and Astronomy, Wayne State University, Detroit, Michigan 48202 (United States); Naik, V. M. [Department of Natural Sciences, University of Michigan-Dearborn, Dearborn, Michigan 48128 (United States); Vaishnava, P. P. [Department of Physics, Kettering University, Flint, Michigan 48504 (United States)

    2014-07-21

    Rate of heat generated by magnetic nanoparticles in a ferrofluid is affected by their magnetic properties, temperature, and viscosity of the carrier liquid. We have investigated temperature dependent magnetic hyperthermia in ferrofluids, consisting of dextran coated superparamagnetic Fe{sub 3}O{sub 4} nanoparticles, subjected to external magnetic fields of various frequencies (188–375 kHz) and amplitudes (140–235 Oe). Transmission electron microscopy measurements show that the nanoparticles are polydispersed with a mean diameter of 13.8 ± 3.1 nm. The fitting of experimental dc magnetization data to a standard Langevin function incorporating particle size distribution yields a mean diameter of 10.6 ± 1.2 nm, and a reduced saturation magnetization (∼65 emu/g) compared to the bulk value of Fe{sub 3}O{sub 4} (∼95 emu/g). This is due to the presence of a finite surface layer (∼1 nm thickness) of non-aligned spins surrounding the ferromagnetically aligned Fe{sub 3}O{sub 4} core. We found the specific absorption rate, measured as power absorbed per gram of iron oxide nanoparticles, decreases monotonically with increasing temperature for all values of magnetic field and frequency. Using the size distribution of magnetic nanoparticles estimated from the magnetization measurements, we have fitted the specific absorption rate versus temperature data using a linear response theory and relaxation dissipation mechanisms to determine the value of magnetic anisotropy constant (28 ± 2 kJ/m{sup 3}) of Fe{sub 3}O{sub 4} nanoparticles.

  8. Theranostic nanoparticles for the treatment of cancer

    Moore, Thomas Lee

    The main focus of this research was to evaluate the ability of a novel multifunctional nanoparticle to mediate drug delivery and enable a non-invasive approach to measure drug release kinetics in situ for the treatment of cancer. These goals were approached by developing a nanoparticle consisting of an inorganic core (i.e. gadolinium sulfoxide doped with europium ions or carbon nanotubes). This was coated with an external amphiphilic polymer shell comprised of a biodegradable polyester (i.e. poly(lactide) or poly(glycolide)), and poly(ethylene glycol) block copolymer. In this system, the inorganic core mediates the imaging aspect, the relatively hydrophobic polyester encapsulates hydrophobic anti-cancer drugs, and poly(ethylene glycol) stabilizes the nanoparticle in an aqueous environment. The synthesis of this nanoparticle drug delivery system utilized a simple one-pot room temperature ring-opening polymerization that neglected the use of potentially toxic catalysts and reduced the number of washing steps. This functionalization approach could be applied across a number of inorganic nanoparticle platforms. Coating inorganic nanoparticles with biodegradable polymer was shown to decrease in vitro and in vivo toxicity. Nanoparticles could be further coated with multiple polymer layers to better control drug release characteristics. Finally, loading polymer coated radioluminescent nanoparticles with photoactive drugs enabled a mechanism for measuring drug concentration in situ. The work presented here represents a step forward to developing theranostic nanoparticles that can improve the treatment of cancer.

  9. Anisotropy effects in magnetic hyperthermia: A comparison between spherical and cubic exchange-coupled FeO/Fe{sub 3}O{sub 4} nanoparticles

    Khurshid, H., E-mail: khurshid@usf.edu, E-mail: sharihar@usf.edu; Nemati, Z.; Phan, M. H.; Mukherjee, P.; Srikanth, H., E-mail: khurshid@usf.edu, E-mail: sharihar@usf.edu [Department of Physics, University of South Florida, Tampa, Florida 33620 (United States); Alonso, J. [Department of Physics, University of South Florida, Tampa, Florida 33620 (United States); BCMaterials Edificio No. 500, Parque Tecnológico de Vizcaya, Derio 48160 (Spain); Fdez-Gubieda, M. L.; Barandiarán, J. M. [BCMaterials Edificio No. 500, Parque Tecnológico de Vizcaya, Derio 48160 (Spain); Depto. Electricidad y Electrónica, Universidad del País Vasco, Leioa 48940 (Spain)

    2015-05-07

    Spherical and cubic exchange-coupled FeO/Fe{sub 3}O{sub 4} nanoparticles, with different FeO:Fe{sub 3}O{sub 4} ratios, have been prepared by a thermal decomposition method to probe anisotropy effects on their heating efficiency. X-ray diffraction and transmission electron microscopy reveal that the nanoparticles are composed of FeO and Fe{sub 3}O{sub 4} phases, with an average size of ∼20 nm. Magnetometry and transverse susceptibility measurements show that the effective anisotropy field is 1.5 times larger for the cubes than for the spheres, while the saturation magnetization is 1.5 times larger for the spheres than for the cubes. Hyperthermia experiments evidence higher values of the specific absorption rate (SAR) for the cubes as compared to the spheres (200 vs. 135 W/g at 600 Oe and 310 kHz). These observations point to an important fact that the saturation magnetization is not a sole factor in determining the SAR and the heating efficiency of the magnetic nanoparticles can be improved by tuning their effective anisotropy.

  10. The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells

    Villanueva, Angeles; Canete, Magdalena; Calero, Macarena; Roca, Alejandro G; Veintemillas-Verdaguer, Sabino; Serna, Carlos J; Del Puerto Morales, Maria; Miranda, Rodolfo

    2009-01-01

    The internalization and biocompatibility of iron oxide nanoparticles surface functionalized with four differently charged carbohydrates have been tested in the human cervical carcinoma cell line (HeLa). Neutral, positive, and negative iron oxide nanoparticles were obtained by coating with dextran, aminodextran, heparin, and dimercaptosuccinic acid, resulting in colloidal suspensions stable at pH 7 with similar aggregate size. No intracellular uptake was detected in cells incubated with neutral charged nanoparticles, while negative particles showed different behaviour depending on the nature of the coating. Thus, dimercaptosuccinic-coated nanoparticles showed low cellular uptake with non-toxic effects, while heparin-coated particles showed cellular uptake only at high nanoparticle concentrations and induced abnormal mitotic spindle configurations. Finally, cationic magnetic nanoparticles show excellent properties for possible in vivo biomedical applications such as cell tracking by magnetic resonance imaging (MRI) and cancer treatment by hyperthermia: (i) they enter into cells with high effectiveness, and are localized in endosomes; (ii) they can be easily detected inside cells by optical microscopy, (iii) they are retained for relatively long periods of time, and (iv) they do not induce any cytotoxicity.

  11. Imaging and modification of the tumor vascular barrier for improvement in magnetic nanoparticle uptake and hyperthermia treatment efficacy

    Hoopes, P. Jack; Petryk, Alicia A.; Tate, Jennifer A.; Savellano, Mark S.; Strawbridge, Rendall R.; Giustini, Andrew J.; Stan, Radu V.; Gimi, Barjor; Garwood, Michael

    2013-02-01

    The predicted success of nanoparticle based cancer therapy is due in part to the presence of the inherent leakiness of the tumor vascular barrier, the so called enhanced permeability and retention (EPR) effect. Although the EPR effect is present in varying degrees in many tumors, it has not resulted in the consistent level of nanoparticle-tumor uptake enhancement that was initially predicted. Magnetic/iron oxide nanoparticles (mNPs) have many positive qualities, including their inert/nontoxic nature, the ability to be produced in various sizes, the ability to be activated by a deeply penetrating and nontoxic magnetic field resulting in cell-specific cytotoxic heating, and the ability to be successfully coated with a wide variety of functional coatings. However, at this time, the delivery of adequate numbers of nanoparticles to the tumor site via systemic administration remains challenging. Ionizing radiation, cisplatinum chemotherapy, external static magnetic fields and vascular disrupting agents are being used to modify the tumor environment/vasculature barrier to improve mNP uptake in tumors and subsequently tumor treatment. Preliminary studies suggest use of these modalities, individually, can result in mNP uptake improvements in the 3-10 fold range. Ongoing studies show promise of even greater tumor uptake enhancement when these methods are combined. The level and location of mNP/Fe in blood and normal/tumor tissue is assessed via histopathological methods (confocal, light and electron microscopy, histochemical iron staining, fluorescent labeling, TEM) and ICP-MS. In order to accurately plan and assess mNP-based therapies in clinical patients, a noninvasive and quantitative imaging technique for the assessment of mNP uptake and biodistribution will be necessary. To address this issue, we examined the use of computed tomography (CT), magnetic resonance imaging (MRI), and Sweep Imaging With Fourier Transformation (SWIFT), an MRI technique which provides a

  12. Characterization of physicochemical and colloidal properties of hydrogel chitosan-coated iron-oxide nanoparticles for cancer therapy

    Catalano, E; Di Benedetto, A

    2017-01-01

    Superparamagnetic iron oxide nanoparticles have recently been investigated for their potential to kill cancer cells with promising results, owing to their ability to be targeted and heated by magnetic fields. In this study, novel hydrogel, chitosan Fe 3 O 4 magnetic nanoparticles were synthesized to induce magnetic hyperthermia, and targeted delivering of chemotherapeutics in the cancer microenvironment. The characteristic properties of synthesized bare and CS-MNPs were analyzed by various analytical methods: X-ray diffraction, Fourier transformed infrared spectroscopy, Scanning electron microscopy and Thermo-gravimetric analysis/differential thermal analysis. Magnetic nanoparticles were successfully synthesized using the co-precipitation method. This synthesis technique resulted in nanoparticles with an average particle size of 16 nm. The pure obtained nanoparticles were then successfully encapsulated with 4-nm-thick chitosan coating. The formation of chitosan on the surface of nanoparticles was confirmed by physicochemical analyses. Heating experiments at safe magnetic field (f = 100 kHz, H =10-20 kA m -1 ) revealed that the maximum achieved temperature of water stable chitosan-coated nanoparticles (50 mg ml -1 ) is fully in agreement with cancer therapy and biomedical applications. (paper)

  13. Characterization of physicochemical and colloidal properties of hydrogel chitosan-coated iron-oxide nanoparticles for cancer therapy

    Catalano, E.; Di Benedetto, A.

    2017-05-01

    Superparamagnetic iron oxide nanoparticles have recently been investigated for their potential to kill cancer cells with promising results, owing to their ability to be targeted and heated by magnetic fields. In this study, novel hydrogel, chitosan Fe3O4 magnetic nanoparticles were synthesized to induce magnetic hyperthermia, and targeted delivering of chemotherapeutics in the cancer microenvironment. The characteristic properties of synthesized bare and CS-MNPs were analyzed by various analytical methods: X-ray diffraction, Fourier transformed infrared spectroscopy, Scanning electron microscopy and Thermo-gravimetric analysis/differential thermal analysis. Magnetic nanoparticles were successfully synthesized using the co-precipitation method. This synthesis technique resulted in nanoparticles with an average particle size of 16 nm. The pure obtained nanoparticles were then successfully encapsulated with 4-nm-thick chitosan coating. The formation of chitosan on the surface of nanoparticles was confirmed by physicochemical analyses. Heating experiments at safe magnetic field (f = 100 kHz, H =10-20 kA m-1) revealed that the maximum achieved temperature of water stable chitosan-coated nanoparticles (50 mg ml-1) is fully in agreement with cancer therapy and biomedical applications.

  14. Cancer nanomedicine: gold nanoparticle mediated combined cancer therapy

    Yang, C.; Bromma, Kyle; Chithrani, B. D.

    2018-02-01

    Recent developments in nanotechnology has provided new tools for cancer therapy and diagnosis. Among other nanomaterial systems, gold nanoparticles are being used as radiation dose enhancers and anticancer drug carriers in cancer therapy. Fate of gold nanoparticles within biological tissues can be probed using techniques such as TEM (transmission electron microscopy) and SEM (Scanning Electron Microscopy) due to their high electron density. We have shown for the first time that cancer drug loaded gold nanoparticles can reach the nucleus (or the brain) of cancer cells enhancing the therapeutic effect dramatically. Nucleus of the cancer cells are the most desirable target in cancer therapy. In chemotherapy, smart delivery of highly toxic anticancer drugs through packaging using nanoparticles will reduce the side effects and improve the quality and care of cancer patients. In radiation therapy, use of gold nanoparticles as radiation dose enhancer is very promising due to enhanced localized dose within the cancer tissue. Recent advancement in nanomaterial characterization techniques will facilitate mapping of nanomaterial distribution within biological specimens to correlate the radiobiological effects due to treatment. Hence, gold nanoparticle mediated combined chemoradiation would provide promising tools to achieve personalized and tailored cancer treatments in the near future.

  15. Three-Dimensional Microwave Hyperthermia for Breast Cancer Treatment in a Realistic Environment Using Particle Swarm Optimization.

    Nguyen, Phong Thanh; Abbosh, Amin; Crozier, Stuart

    2017-06-01

    In this paper, a technique for noninvasive microwave hyperthermia treatment for breast cancer is presented. In the proposed technique, microwave hyperthermia of patient-specific breast models is implemented using a three-dimensional (3-D) antenna array based on differential beam-steering subarrays to locally raise the temperature of the tumor to therapeutic values while keeping healthy tissue at normal body temperature. This approach is realized by optimizing the excitations (phases and amplitudes) of the antenna elements using the global optimization method particle swarm optimization. The antennae excitation phases are optimized to maximize the power at the tumor, whereas the amplitudes are optimized to accomplish the required temperature at the tumor. During the optimization, the technique ensures that no hotspots exist in healthy tissue. To implement the technique, a combination of linked electromagnetic and thermal analyses using MATLAB and the full-wave electromagnetic simulator is conducted. The technique is tested at 4.2 GHz, which is a compromise between the required power penetration and focusing, in a realistic simulation environment, which is built using a 3-D antenna array of 4 × 6 unidirectional antenna elements. The presented results on very dense 3-D breast models, which have the realistic dielectric and thermal properties, validate the capability of the proposed technique in focusing power at the exact location and volume of tumor even in the challenging cases where tumors are embedded in glands. Moreover, the models indicate the capability of the technique in dealing with tumors at different on- and off-axis locations within the breast with high efficiency in using the microwave power.

  16. Modification of radiosensitivity of mammalian cells by means of hyperthermia and chemical agent. Coordinated programme on improvement of cancer therapy by the combination of treatment by conventional radiation and physical or chemical means

    Djordjevic, O.

    1984-11-01

    The effect of the treatment of the cultured mammalian cells with a relatively new anti-cancer drug teniposide (VM26), radiation (4 Gy), hyperthermia (42 deg. C and 45 deg. C) and caffeine, in various combinations, has been studied. The following conclusions can be drawn from the data obtained: The cultured mammalian cells respond to the anti-cancer drug VM26 treatment in a dose and time dependent manner. Significant potentiation of cell killing was demonstrated when they are exposed simultaneously to VM26 and hyperthermia. Post-treatment incubation of the cells in non-toxic concentration of caffeine (2 mM) has produced a marked potentiation of the lethal effect, indicating that caffeine interferes with the repair processes in these cells. Combination of VM26, hyperthermia and caffeine produced a maximum killing effect compared to VM26 treatment only. When the cells are exposed to initial (90 min. at 42 deg. C or 40 min. at 45 deg. C) and subsequent hyperthermia (60 min. at 42 deg. C or 60 min. at 45 deg. C) the thermotolerance will develop depending on the degree of initial and subsequent temperature. The combination of hyperthermia with irradiation results in a potentiation of the effect of treatment compared to the treatment with only irradiation or hyperthermia. Maximum killing of the cells will be obtained when irradiation is applied immediately after hyperthermia. The results obtained should be regarded as useful in case of clinical application of the tested agents

  17. Re-irradiation of the chest wall for local breast cancer recurrence. Results of salvage brachytherapy with hyperthermia

    Auoragh, A. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Hospital Fuerth, Department of Radiation Oncology, Fuerth (Germany); Strnad, V.; Ott, O.J.; Fietkau, R. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Beckmann, M.W. [University Hospital Erlangen, Department of Gynecology and Obstetrics, Erlangen (Germany)

    2016-09-15

    Following mastectomy and adjuvant external beam radiation therapy in patients with breast cancer, the incidence of local or locoregional recurrence is approximately 9 % (2-20 %). Alongside the often limited possibilities of surgical treatment, radiation therapy combined with superficial hyperthermia is the most effective local therapy. In the present work, a retrospective analysis of salvage brachytherapy combined with superficial hyperthermia for chest wall recurrences is presented. Between 2004 and 2011, 18 patients with a total of 23 target volumes resulting from chest wall recurrences after previously mastectomy and external beam radiation therapy (median 56 Gy, range 50-68 Gy) were treated with superficial brachytherapy as salvage treatment: 8 patients (44 %) had macroscopic tumor, 3 (17 %) had microscopic tumor (R1), and 7 (39 %) had undergone R0 resection and were treated due to risk factors. A dose of 50 Gy was given (high-dose rate [HDR] and pulsed-dose rate [PDR] procedures). In all, 5 of 23 patients (22 %) received additional concurrent chemotherapy, and in 20 of 23 (87 %) target volumes additional superficial hyperthermia was carried out twice weekly. The 5-year local recurrence-free survival was 56 %, the disease-free survival was 28 %, and a 5-year overall survival was 22 %. Late side effects Common Toxicity Criteria (CTC) grade 3 were reported in 17 % of the patients: 2 of 18 (11 %) had CTC grade 3 fibrosis, and 1 of 18 (6 %) had a chronic wound healing disorder. Re-irradiation as salvage brachytherapy with superficial hyperthermia for chest wall recurrences is a feasible and safe treatment with good local control results and acceptable late side effects. (orig.) [German] Nach einer Mastektomie und adjuvanter Strahlentherapie bei Patientinnen mit Mammakarzinom kommt es bei 9 % (2-20 %) zum lokalen bzw. lokoregionaeren Rezidiv. Neben den oft limitierten operativen Behandlungsmoeglichkeiten ist die Strahlentherapie mit Oberflaechenhyperthermie die

  18. Synthesis and magnetic properties of Co.sub.1-x./sub.Zn.sub.x./sub.Fe.sub.2./sub.O.sub.4+γ./sub. nanoparticles as materials for magnetic fluid hyperthermia

    Veverka, Miroslav; Veverka, Pavel; Jirák, Zdeněk; Kaman, Ondřej; Knížek, Karel; Maryško, Miroslav; Pollert, Emil; Závěta, Karel

    2010-01-01

    Roč. 322, č. 16 (2010), s. 2386-2389 ISSN 0304-8853 R&D Projects: GA AV ČR KAN200200651; GA AV ČR KJB100100701; GA MŠk MEB090901 Institutional research plan: CEZ:AV0Z10100521 Keywords : magnetic nanoparticle * cobalt zinc ferrite * precipitation * magnetic behavior * magnetic fluid hyperthermia Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.689, year: 2010

  19. Hyperthermia and radiotherapy

    Fitspatrick, C.

    1990-01-01

    Hyperthermia and radiotherapy have for long been used to assist in the control of tumours, either as separate entities, or, in a combined treatment scheme. This paper outlines why hyperthermia works, thermal dose and the considerations required in the timing when hyperthermia is combined with radiotherapy. Previously reported results for hyperthermia and radiotherapy used together are also presented. 8 refs., 8 tabs

  20. Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease

    Feyerabend, Thomas; Wiedemann, Guenter Joseph; Jaeger, Birgit; Vesely, Hugo; Mahlmann, Birgit; Richter, Eckart

    2001-04-01

    Purpose: To investigate the feasibility and effectiveness of radiochemothermotherapy (triple-modality therapy) in patients with inoperable recurrent breast cancer. Patients and Methods: Patients with inoperable recurrent lesions, World Health Organization (WHO) performance status of 2 or greater, life expectancy of more than 3 months, adequate bone marrow, hepatic and renal function were eligible for this Phase I/II study. Conventionally fractionated or hyperfractionated radiotherapy (RT) was performed. Once-weekly local hyperthermia (HT) combined with chemotherapy (CT; epirubicin 20 mg/m{sup 2}, ifosfamide 1.5 g/m{sup 2}) was applied within 30 min after RT. Results: Twenty-five patients, all heavily pretreated (18/25 preirradiated), received a mean total dose of 49 Gy. The median number of HT/CT sessions was 4. Skin toxicity was low, whereas bone marrow toxicity was significant (leucopenia Grade 3/4 in 14/1 patients). The overall response rate was 80% with a complete response (CR) rate of 44%. Response rates in patients with noninflammatory disease (n=14; CR 10 patients, partial response [PR] 3 patients) were far better than in patients with inflammatory disease (n=11; CR 1 patient, PR 6 patients). Conclusions: In patients with recurrent breast cancer, triple-modality therapy is feasible with acceptable toxicity. High remission rates can be achieved in noninflammatory disease, however, local control is limited to a few months. Whether the addition of chemotherapy has a clear-cut advantage to radiothermotherapy alone remains an open question.

  1. Local hyperthermia, radiation, and chemotherapy in recurrent breast cancer is feasible and effective except for inflammatory disease

    Feyerabend, Thomas; Wiedemann, Guenter Joseph; Jaeger, Birgit; Vesely, Hugo; Mahlmann, Birgit; Richter, Eckart

    2001-01-01

    Purpose: To investigate the feasibility and effectiveness of radiochemothermotherapy (triple-modality therapy) in patients with inoperable recurrent breast cancer. Patients and Methods: Patients with inoperable recurrent lesions, World Health Organization (WHO) performance status of 2 or greater, life expectancy of more than 3 months, adequate bone marrow, hepatic and renal function were eligible for this Phase I/II study. Conventionally fractionated or hyperfractionated radiotherapy (RT) was performed. Once-weekly local hyperthermia (HT) combined with chemotherapy (CT; epirubicin 20 mg/m 2 , ifosfamide 1.5 g/m 2 ) was applied within 30 min after RT. Results: Twenty-five patients, all heavily pretreated (18/25 preirradiated), received a mean total dose of 49 Gy. The median number of HT/CT sessions was 4. Skin toxicity was low, whereas bone marrow toxicity was significant (leucopenia Grade 3/4 in 14/1 patients). The overall response rate was 80% with a complete response (CR) rate of 44%. Response rates in patients with noninflammatory disease (n=14; CR 10 patients, partial response [PR] 3 patients) were far better than in patients with inflammatory disease (n=11; CR 1 patient, PR 6 patients). Conclusions: In patients with recurrent breast cancer, triple-modality therapy is feasible with acceptable toxicity. High remission rates can be achieved in noninflammatory disease, however, local control is limited to a few months. Whether the addition of chemotherapy has a clear-cut advantage to radiothermotherapy alone remains an open question

  2. Induction of Localized Hyperthermia by Millisecond Laser Pulses in the Presence of Gold-Gold Sulphide Nanoparticles in a Phantom

    Zahra Shahamat

    2015-05-01

    Full Text Available Introduction Application of near-infrared absorbing nanostructures can induce hyperthermia, in addition to providing more efficient  photothermal effects. Gold-gold sulfide (GGS is considered as one of these nanostructures. This study was performed on a tissue-equivalent optical-thermal phantom to determine the temperature profile in the presence and absence of GGS and millisecond pulses of a near-infrared laser. Moreover, the feasibility of hyperthermia induction was investigated in a simulated tumor. Materials and Methods A tumor with its surrounding tissues was simulated in a phantom made of Agarose and Intralipid. The tumor was irradiated by 30 laser pulses with durations of 30, 100, and 400 ms and fluences of 40 and 60 J/cm2. Temperature variations in the phantom with and without GGS were recorded, using fast-response sensors of a digital thermometer, placed at different distances from the central axis at three depths. The temperature rise was recorded by varying duration and fluence of the laser pulses. Results The rise in temperature was recorded by increasing laser fluence and number of pulses for three durations. The temperature profile was obtained at each depth. The presence of GGS resulted in a significant increase in temperature in all cases (P

  3. Improvement of locoregional hyperthermia treatments of oesophageal cancer using treatment planning

    Kok, H.P.; Haaren Van, P.M.A.; Kamer Van de, J.B.; Zum Voerde Sive Voerding, P.J.; Wiersma, J.; Hulshof, M.C.C.M; Geijsen, E.D.; Crezee, J.

    2005-01-01

    Full text: The thermal dose achieved in the clinic often remains too low due to the incidence of treatment limiting hot spots, which are difficult to avoid intuitively due to the large number of degrees of freedom (amplitudes and phases) of the heating device. To improve hyperthermia treatments of oesophagus carcinoma patients with the 70 MHz AMC-4 waveguide system we performed hyperthermia treatment planning (HTP) with high resolution temperature based optimization. With this optimization we obtain amplitude (A) and phase (p) settings for the antennas for optimal tumor heating (> 43 o C) while preventing hot spots in normal tissue ( o C) and maintaining the spinal cord temperature below 40 o C to prevent neurotoxicity. With the mixed A/P settings the highest absolute ΔT's were achieved, while the ratio was not much different from the other two configurations. This implies that with these settings the same tumor heating can be obtained with less applied power, resulting in more efficient heating. The fact that the combined numerical A/clinical P settings resulted in the highest absolute temperature rises in the oesophagus might be due to the difference in patient positioning between the planning and the actual treatment, since the location of the SAR focus in the tumor is constructed mainly by phase steering. The temperature rise near the spinal cord depends mainly on the power of the top antenna. The correlation coefficient was R=0.37, which was considerably higher than the correlation with the powers or phases of the other antennas. The temperature rise in the oesophagus depends mainly on the power of the top and bottom antenna together. The correlation coefficient was only R=0.12 but this was still more than 2 times higher than the correlation with the power of the left and right antenna. The relation between the temperature rise due to a power pulse of 30 seconds and the achieved steady state temperature was more or less linear, implying a higher T 90 and T 50

  4. Improvement of locoregional hyperthermia treatments of oesophageal cancer using treatment planning

    Kok, H P; Haaren Van, P M.A.; Kamer Van de, J B; Zum Voerde Sive Voerding, P.J.; Wiersma, J; Hulshof, M C.C.M; Geijsen, E D; Crezee, J [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam (Netherlands)

    2005-07-01

    Full text: The thermal dose achieved in the clinic often remains too low due to the incidence of treatment limiting hot spots, which are difficult to avoid intuitively due to the large number of degrees of freedom (amplitudes and phases) of the heating device. To improve hyperthermia treatments of oesophagus carcinoma patients with the 70 MHz AMC-4 waveguide system we performed hyperthermia treatment planning (HTP) with high resolution temperature based optimization. With this optimization we obtain amplitude (A) and phase (p) settings for the antennas for optimal tumor heating (> 43 {sup o}C) while preventing hot spots in normal tissue (< 42 {sup o}C) and maintaining the spinal cord temperature below 40 {sup o}C to prevent neurotoxicity. With the mixed A/P settings the highest absolute {delta}T's were achieved, while the ratio was not much different from the other two configurations. This implies that with these settings the same tumor heating can be obtained with less applied power, resulting in more efficient heating. The fact that the combined numerical A/clinical P settings resulted in the highest absolute temperature rises in the oesophagus might be due to the difference in patient positioning between the planning and the actual treatment, since the location of the SAR focus in the tumor is constructed mainly by phase steering. The temperature rise near the spinal cord depends mainly on the power of the top antenna. The correlation coefficient was R=0.37, which was considerably higher than the correlation with the powers or phases of the other antennas. The temperature rise in the oesophagus depends mainly on the power of the top and bottom antenna together. The correlation coefficient was only R=0.12 but this was still more than 2 times higher than the correlation with the power of the left and right antenna. The relation between the temperature rise due to a power pulse of 30 seconds and the achieved steady state temperature was more or less linear

  5. Noble Metal Nanoparticles Applications in Cancer

    João Conde

    2012-01-01

    Full Text Available Nanotechnology has prompted new and improved materials for biomedical applications with particular emphasis in therapy and diagnostics. Special interest has been directed at providing enhanced molecular therapeutics for cancer, where conventional approaches do not effectively differentiate between cancerous and normal cells; that is, they lack specificity. This normally causes systemic toxicity and severe and adverse side effects with concomitant loss of quality of life. Because of their small size, nanoparticles can readily interact with biomolecules both at surface and inside cells, yielding better signals and target specificity for diagnostics and therapeutics. This way, a variety of nanoparticles with the possibility of diversified modification with biomolecules have been investigated for biomedical applications including their use in highly sensitive imaging assays, thermal ablation, and radiotherapy enhancement as well as drug and gene delivery and silencing. Here, we review the available noble metal nanoparticles for cancer therapy, with particular focus on those already being translated into clinical settings.

  6. Microwave beamforming for non-invasive patient-specific hyperthermia treatment of pediatric brain cancer

    Burfeindt, Matthew J; Zastrow, Earl; Hagness, Susan C; Van Veen, Barry D; Medow, Joshua E

    2011-01-01

    We present a numerical study of an array-based microwave beamforming approach for non-invasive hyperthermia treatment of pediatric brain tumors. The transmit beamformer is designed to achieve localized heating-that is, to achieve constructive interference and selective absorption of the transmitted electromagnetic waves at the desired focus location in the brain while achieving destructive interference elsewhere. The design process takes into account patient-specific and target-specific propagation characteristics at 1 GHz. We evaluate the effectiveness of the beamforming approach using finite-difference time-domain simulations of two MRI-derived child head models from the Virtual Family (IT'IS Foundation). Microwave power deposition and the resulting steady-state thermal distribution are calculated for each of several randomly chosen focus locations. We also explore the robustness of the design to mismatch between the assumed and actual dielectric properties of the patient. Lastly, we demonstrate the ability of the beamformer to suppress hot spots caused by pockets of cerebrospinal fluid (CSF) in the brain. Our results show that microwave beamforming has the potential to create localized heating zones in the head models for focus locations that are not surrounded by large amounts of CSF. These promising results suggest that the technique warrants further investigation and development.

  7. Combination (RaHPP) of radiotherapy, hyperthermia and chemotherapy (peplomycin and picibanil) for bladder cancer

    Washida, Hiroto; Tsugaya, Masayuki; Hirao, Noriaki; Hachisuka, Yusuke

    1984-09-01

    Four patients with urinary bladder carcinoma were treated by combination therapy which consisted of hyperthermia vesical irrigation of two anticancer drugs (peplomycin and picibanil), intravesical instillation of those drugs and radiation. Following the therapeutic method we planned, 40 mg of peplomycin and 10 KE of picibanil in 1,500 ml of sterile distilled water was irrigated at 42 to 43/sup 0/C into the bladder for 3 hours; 40 mg of peplomycin and 10 KE of picibanil in 40 ml of sterile distilled water was instilled into the bladder; and, the focus was irradiated with /sup 60/Co to a focal dose of 200 rad 30 minutes later. This pattern of treatment was repeated once a week, 3 to 5 times in total. On the days this pattern was not taken, 5 KE of picibanil in 20 ml of sterile distilled water was instilled into the bladder cavity. Complete response was observed in one patient and partial response in 3 patients. The side effect was temporary irritable bladder symptom. (author).

  8. Combination (RaHPP) of radiotherapy, hyperthermia and chemotherapy (peplomycin and picibanil) for bladder cancer

    Washida, Hiroto; Tsugaya, Masayuki; Hirao, Noriaki; Hachisuka, Yusuke

    1984-01-01

    Four patients with urinary bladder carcinoma were treated by combination therapy which consisted of hyperthermia vesical irrigation of two anticancer drugs (peplomycin and picibanil), intravesical instillation of those drugs and radiation. Following the therapeutic method we planned, 40 mg of peplomycin and 10 KE of picibanil in 1,500 ml of sterile distilled water was irrigated at 42 to 43 0 C into the bladder for 3 hours; 40 mg of peplomycin and 10 KE of picibanil in 40 ml of sterile distilled water was instilled into the bladder; and, the focus was irradiated with 60 Co to a focal dose of 200 rad 30 minutes later. This pattern of treatment was repeated once a week, 3 to 5 times in total. On the days this pattern was not taken, 5 KE of picibanil in 20 ml of sterile distilled water was instilled into the bladder cavity. Complete response was observed in one patient and partial response in 3 patients. The side effect was temporary irritable bladder symptom. (author)

  9. The Role of Bcl-xL in Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia on Human Colon Cancer

    Song, Xinxin; Kim, Seog-Young; Lee, Yong J.

    2012-01-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world. The main cause of death of colorectal cancer is hepatic metastases which can be treated using isolated hepatic perfusion (IHP), allowing treatment of colorectal metastasis with various methods. In this study we present a novel potent multimodality strategy comprising humanized death receptor 4 (DR4) antibody mapatumumab (Mapa) in combination with oxaliplatin and hyperthermia to treat human colon cancer cells. Oxaliplatin and hyperthermia sensitized colon cancer cells to Mapa in the mitochondrial dependent apoptotic pathway and increased reactive oxygen species production, leading to Bcl-xL phosphorylation at Serine 62 in a c-Jun N-terminal kinase (JNK)-dependent manner. Overexpression of Bcl-xL reduced the efficacy of the multimodality treatment, while phosphorylation of Bcl-xL decreased its anti-apoptotic activity. The multimodality treatment dissociated Bcl-xL from Bax, allowing Bax oligomerization to induce cytochrome c release from mitochondria. In addition, the multimodality treatment significantly inhibited colorectal cancer xenografts’ tumor growth. The successful outcome of this study will support the application of multimodality strategy to colorectal hepatic metastases. PMID:23051936

  10. Influence of the aggregation, concentration, and viscosity on the nanomagnetism of iron oxide nanoparticle colloids for magnetic hyperthermia

    Cabrera, David; Camarero, Julio; Ortega, Daniel; Teran, Francisco J.

    2015-01-01

    Iron oxide nanoparticles have become ubiquitous in many biomedical applications, acting as core elements in an increasing number of therapeutic and diagnostic modalities. These applications mainly rely on their static and dynamic magnetic properties, through which they can be remotely actuated. However, little attention has been paid to understand the variation of the magnetic response of nanoparticles inside cells or tissues, despite of the remarkable changes reported to date. In this article, we provide some hints to analyze the influence of the biological matrix on the magnetism of iron oxide nanoparticles. To this aim, we propose the assessment of the heating efficiency of magnetic colloids against nanoparticle aggregation, concentration, and viscosity in order to mimic the fate of nanoparticles upon cell internalization

  11. Influence of the aggregation, concentration, and viscosity on the nanomagnetism of iron oxide nanoparticle colloids for magnetic hyperthermia

    Cabrera, David; Camarero, Julio; Ortega, Daniel; Teran, Francisco J., E-mail: francisco.teran@imdea.org [Ciudad Universitaria de Cantoblanco, IMDEA Nanociencia (Spain)

    2015-03-15

    Iron oxide nanoparticles have become ubiquitous in many biomedical applications, acting as core elements in an increasing number of therapeutic and diagnostic modalities. These applications mainly rely on their static and dynamic magnetic properties, through which they can be remotely actuated. However, little attention has been paid to understand the variation of the magnetic response of nanoparticles inside cells or tissues, despite of the remarkable changes reported to date. In this article, we provide some hints to analyze the influence of the biological matrix on the magnetism of iron oxide nanoparticles. To this aim, we propose the assessment of the heating efficiency of magnetic colloids against nanoparticle aggregation, concentration, and viscosity in order to mimic the fate of nanoparticles upon cell internalization.

  12. Folate attached, curcumin loaded Fe{sub 3}O{sub 4} nanoparticles: A novel multifunctional drug delivery system for cancer treatment

    Thu Huong, Le Thi [Institute of Materials Science, Ha Noi 844 (Viet Nam); Vietnam National University of Agriculture, Ha Noi 844 (Viet Nam); Nam, Nguyen Hoai, E-mail: nhnam@ims.vast.ac.vn [Institute of Materials Science, Ha Noi 844 (Viet Nam); Doan, Do Hai [Institute of Materials Science, Ha Noi 844 (Viet Nam); My Nhung, Hoang Thi [Hanoi University of Science, Vietnam National University, Ha Noi 844 (Viet Nam); Quang, Bui Thuc [National Gegiatrics Hospital, Ha Noi 844 (Viet Nam); Nam, Pham Hong; Thong, Phan Quoc; Phuc, Nguyen Xuan [Institute of Materials Science, Ha Noi 844 (Viet Nam); Thu, Ha Phuong, E-mail: thuhp@ims.vast.ac.vn [Institute of Materials Science, Ha Noi 844 (Viet Nam)

    2016-04-01

    Study and development of drug delivery nanosystem for cancer treatment are attracting great attention in recent years. In this work, we studied the role of folic acid as a targeting factor on magnetic nanoparticle Fe{sub 3}O{sub 4} based curcumin loading nanosystem. Characteristics of the nanosystems were investigated by Fourier transform infrared spectroscopy (FTIR) and field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), thermal gravimetric analysis (TGA) and vibrating sample magnetometer (VSM), while targeting role of folic was accessed in vivo on tumor bearing mice. The results showed that folate attached Fe{sub 3}O{sub 4} based curcumin loading nanosystem has very small size and exhibits better targeting effect compared to the counterpart without folate. In addition, magnetic induction heating of this nanosystem evidenced its potential for cancer hyperthermia. - Highlights: • Folate attached, curcumin loaded Fe3O4 nanoparticles were prepared and characterized. • The NPs have high curcumin loading capacity and good ability for hyperthermia. • Folate shows its bioactivity of effectively targeting the NPs to tumor tissues. • Chemotherapy, hyperthermia and targeting factor are all well combined in the NPs.

  13. Application and possible mechanisms of combining LLLT (low level laser therapy), infrared hyperthermia and ionizing radiation in the treatment of cancer

    Abraham, Edward H.; Woo, Van H.; Harlin-Jones, Cheryl; Heselich, Anja; Frohns, Florian

    2014-02-01

    Benefit of concomitant infrared hyperthermia and low level laser therapy and ionizing radiation is evaluated in this study. The purpose/objectives: presentation with locally advanced bulky superficial tumors is clinically challenging. To enhance the efficacy of chemotherapy and IMRT (intensity-modulated radiation therapy) and/or electron beam therapy we have developed an inexpensive and clinically effective infrared hyperthermia approach that combines black-body infrared radiation with halogen spectrum radiation and discrete wave length infrared clinical lasers LLLT. The goal is to produce a composite spectrum extending from the far infrared to near infrared and portions of the visible spectrum with discrete penetrating wavelengths generated by the clinical infrared lasers with frequencies of 810 nm and/or 830 nm. The composite spectrum from these sources is applied before and after radiation therapy. We monitor the surface and in some cases deeper temperatures with thermal probes, but use an array of surface probes as the limiting safe thermal constraint in patient treatment while at the same time maximizing infrared entry to deeper tissue layers. Fever-grade infrared hyperthermia is produced in the first centimeters while non-thermal infrared effects act at deeper tissue layers. The combination of these effects with ionizing radiation leads to improved tumor control in many cancers.

  14. Regional hyperthermia combined with radiotherapy for locally advanced non-small cell lung cancers. A multi-institutional prospective randomized trial of the International Atomic Energy Agency

    Mitsumori, Michihide; Hiraoka, Masahiro; Zeng Zhifan; Oliynychenko, P.; Park, Jeong-Ho; Choi, Ihl-Bohng; Tatsuzaki, Hideo; Tanaka, Yoshiaki

    2007-01-01

    An International Atomic Energy Agency (IAEA)-sponsored, multi-institutional prospective randomized trial was conducted to clarify whether the combination of hyperthermia and radiotherapy improves the local response rate of locally advanced non-small cell lung cancer (NSCLC) compared with that obtained by radiotherapy alone. Between October 1998 and April 2002, 80 patients with locally advanced NSCLC were randomized to receive either standard radiation therapy alone (RT) or radiation therapy combined with hyperthermia (RT+HT). The primary endpoint was the local response rate. The secondary endpoints were local progression-free survival and overall survival. The median follow-up period was 204 days for all patients and 450 days for surviving patients. There were no significant differences between the two arms with regard to local response rate (P=0.49) or overall survival rate (P=0.868). However, local progression-free survival was significantly better in the RT+HT arm (P=0.036). Toxicity was generally mild and no grade 3 late toxicity was observed in either arm. Although improvement of local progression-free survival was observed in the RT+HT arm, this prospective randomized study failed to show any substantial benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced NSCLC. (author)

  15. Drug loaded magnetic nanoparticles for cancer therapy

    Jurgons, R; Seliger, C; Hilpert, A; Trahms, L; Odenbach, S; Alexiou, C

    2006-01-01

    Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. In medicine they are used for several approaches such as magnetic cell separation or magnetic resonance imaging (MRI). The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is the focus of medical research, especially for the treatment of cancer and diseases of the vascular system. In an experimental cancer model, we performed targeted drug delivery and used magnetic iron oxide nanoparticles, bound to a chemotherapeutic agent, which were attracted to an experimental tumour in rabbits by an external magnetic field (magnetic drug targeting). Complete tumour remission could be achieved. An important advantage of these carriers is the possibility for detecting these nanoparticles after treatment with common imaging techniques (i.e. x-ray-tomography, magnetorelaxometry, magnetic resonance imaging), which can be correlated to histology

  16. Optimizing magnetic anisotropy of La{sub 1−x}Sr{sub x}MnO{sub 3} nanoparticles for hyperthermia applications

    Rashid, Amin ur [Magnetism Laboratory, Department of Physics, COMSATS Institute of Information Technology, Islamabad (Pakistan); Department of Applied Physical and Material Sciences, University of Swat, Khyber Pakhtunkhwa (Pakistan); Manzoor, Sadia, E-mail: sadia_manzoor@comsats.edu.pk [Magnetism Laboratory, Department of Physics, COMSATS Institute of Information Technology, Islamabad (Pakistan)

    2016-12-15

    Maximizing the magnetothermal response of magnetic nanoparticles (MNP's) for hyperthermia applications is a complex problem, because it depends sensitively upon interrelated magnetic and structural parameters. The task is somewhat simpler for systems with fixed composition, e.g. Fe{sub 3}O{sub 4} or CoFe{sub 2}O{sub 4}, in which the particle size is the only means of modifying the magnetic anisotropy, and hence the magnetothermal response. In the La{sub 1−x}Sr{sub x}MnO{sub 3} system however, the magnetic interactions as well as the particle size both change with the Sr concentration x, which makes it a much more complex system for which to optimize the hyperthermia response. We have investigated the effect of magnetic anisotropy on the magnetothermal response of La{sub 1−x}Sr{sub x}MnO{sub 3} nanoparticles as a function of the particle size as well as the Sr concentration x where 0.20≤x≤0.45. The optimum particle size range is 25–30 nm for all concentrations, where the specific absorption rate (SAR) has a maximum. The linear response theory (LRT) has been applied to this system and good agreement has been found between the experimental and theoretically determined values of the SAR for samples lying in the single domain regime and having large enough anisotropy energies. The agreement is much better for the intermediate concentrations of 0.27 and 0.33, because of their large anisotropy as compared to other concentrations. It is concluded that the LRT can be successfully used to predict the SAR of these nanoparticles, provided they possess large enough effective anisotropies. Values of the ILP have been obtained for these samples and found to be comparable to those of magnetite and some commercial ferrofluids. - Highlights: • For La{sub 1-x}Sr{sub x}MnO{sub 3} system, the magnetic anisotropy is determined not only by the particle size, but also by the strontium content x, we made a systematic study of both these parameters on its magnetothermal

  17. Advances in cancer therapy through the use of carbon nanotube-mediated targeted hyperthermia

    Iancu C

    2011-08-01

    Full Text Available Cornel Iancu, Lucian Mocan3rd Surgery Clinic, Department of Nanomedicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, RomaniaAbstract: Carbon nanotubes (CNTs are emerging versatile tools in nanomedicine applications, particularly in the field of cancer targeting. Due to diverse surface chemistry and unique thermal properties, CNTs can act as strong optical absorbers in near infrared light where biological systems prove to be highly transparent. The process of laser-mediated ablation of cancer cells marked with biofunctionalized CNTs is frequently termed “nanophotothermolysis.” This paper illustrates the potential of engineered CNTs as laser-activated photothermal agents for the selective nanophotothermolysis of cancer cells.Keywords: carbon nanotubes, cancer targeting, functionalization, optical excitation, cancer treatment

  18. Physical mechanism and modeling of heat generation and transfer in magnetic fluid hyperthermia through Néelian and Brownian relaxation: a review.

    Suriyanto; Ng, E Y K; Kumar, S D

    2017-03-23

    Current clinically accepted technologies for cancer treatment still have limitations which lead to the exploration of new therapeutic methods. Since the past few decades, the hyperthermia treatment has attracted the attention of investigators owing to its strong biological rationales in applying hyperthermia as a cancer treatment modality. Advancement of nanotechnology offers a potential new heating method for hyperthermia by using nanoparticles which is termed as magnetic fluid hyperthermia (MFH). In MFH, superparamagnetic nanoparticles dissipate heat through Néelian and Brownian relaxation in the presence of an alternating magnetic field. The heating power of these particles is dependent on particle properties and treatment settings. A number of pre-clinical and clinical trials were performed to test the feasibility of this novel treatment modality. There are still issues yet to be solved for the successful transition of this technology from bench to bedside. These issues include the planning, execution, monitoring and optimization of treatment. The modeling and simulation play crucial roles in solving some of these issues. Thus, this review paper provides a basic understanding of the fundamental and rationales of hyperthermia and recent development in the modeling and simulation applied to depict the heat generation and transfer phenomena in the MFH.

  19. Malignant hyperthermia

    Pollock Neil

    2007-04-01

    Full Text Available Abstract Malignant hyperthermia (MH is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with

  20. Mg shallow doping effects on the ac magnetic self-heating characteristics of γ-Fe2O3 superparamagnetic nanoparticles for highly efficient hyperthermia

    Jang, Jung-tak; Bae, Seongtae

    2017-10-01

    The effects of Mg doping on the magnetic and AC self-heating temperature rising characteristics of γ-Fe2O3 superparamagnetic nanoparticles (SPNPs) were investigated for hyperthermia applications in biomedicine. The doping concentration of nonmagnetic Mg2+ cation was systematically controlled from 0 to 0.15 at. % in Mgx-γFe2O3 SPNPs during chemically and thermally modified one-pot thermal decomposition synthesis under bubbling O2/Ar gas mixture. It was empirically observed that the saturation magnetization (Ms) and the out-of-phase magnetic susceptibility ( χm″)of Mgx-γFe2O3 SPNPs were increased by increasing the Mg2+ cation doping concentration from 0.05 to 0.13 at. %. Correspondingly, the AC magnetically induced self-heating temperature (Tac,max) in solid state and the intrinsic loss power in water were increased up to 184 °C and 14.2 nH m2 kg-1 (Mgx-γFe2O3, x = 0.13), respectively, at the biologically and physiologically safe range of AC magnetic field (Happl × fappl = 1.2 × 109 A m-1 s-1). All the chemically and physically analyzed results confirmed that the dramatically improved AC magnetic induction heating characteristics and the magnetic properties of Mgx-γFe2O3 SPNPs (x = 0.13) are primarily due to the significantly enhanced magnetic susceptibility (particularly, χm″) and the improved AC/DC magnetic softness (lower AC/DC magnetic anisotropy) resulting from the systematically controlled nonmagnetic Mg2+ cation concentrations and distributions (occupation ratio) in the Fe vacancy sites of γ-Fe2O3 (approximately 12% vacancy), instead of typically well-known Fe3O4 (no vacancy) SPNPs. The cell viability and biocompatibility with U87 MG cell lines demonstrated that Mgx-γFe2O3 SPNPs (x = 0.13) has promising bio-feasibility for hyperthermia agent applications.

  1. Multifunctional nanoparticles for prostate cancer therapy.

    Chandratre, Shantanu S; Dash, Alekha K

    2015-02-01

    The relapse of cancer after first line therapy with anticancer agents is a common occurrence. This recurrence is believed to be due to the presence of a subpopulation of cells called cancer stem cells in the tumor. Therefore, a combination therapy which is susceptible to both types of cells is desirable. Delivery of this combinatorial approach in a nanoparticulate system will provide even a better therapeutic outcome in tumor targeting. The objective of this study was to develop and characterize nanoparticulate system containing two anticancer agents (cyclopamine and paclitaxel) having different susceptibilities toward cancer cells. Both drugs were entrapped in glyceryl monooleate (GMO)-chitosan solid lipid as well as poly(glycolic-lactic) acid (PLGA) nanoparticles. The cytotoxicity studies were performed on DU145, DU145 TXR, and Wi26 A4 cells. The particle size of drug-loaded GMO-chitosan nanoparticles was 278.4 ± 16.4 nm with a positive zeta potential. However, the PLGA particles were 234.5 ± 6.8 nm in size with a negative zeta potential. Thermal analyses of both nanoparticles revealed that the drugs were present in noncrystalline state in the matrix. A sustained in vitro release was observed for both the drugs in these nanoparticles. PLGA blank particles showed no cytotoxicity in all the cell lines tested, whereas GMO-chitosan blank particles showed substantial cytotoxicity. The types of polymer used for the preparation of nanoparticles played a major role and affected the in vitro release, cytotoxicity, and uptake of nanoparticles in the all the cell lines tested.

  2. Aptamer conjugated paclitaxel and magnetic fluid loaded fluorescently tagged PLGA nanoparticles for targeted cancer therapy

    Aravind, Athulya; Nair, Remya; Raveendran, Sreejith; Veeranarayanan, Srivani; Nagaoka, Yutaka; Fukuda, Takahiro; Hasumura, Takahashi; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D., E-mail: sakthi@toyo.jp

    2013-10-15

    Controlled and targeted drug delivery is an essential criterion in cancer therapy to reduce the side effects caused by non-specific drug release and toxicity. Targeted chemotherapy, sustained drug release and optical imaging have been achieved using a multifunctional nanocarrier constructed from poly (D, L-lactide-co-glycolide) nanoparticles (PLGA NPs), an anticancer drug paclitaxel (PTX), a fluorescent dye Nile red (NR), magnetic fluid (MF) and aptamers (Apt, AS1411, anti-nucleolin aptamer). The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs (MF-PTX-NR-PLGA NPs) were synthesized by a single-emulsion technique/solvent evaporation method using a chemical cross linker bis (sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. Targeting aptamers were then introduced to the particles through the reaction with the cross linker to target the nucleolin receptors over expressed on the cancer cell surface. Specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently tagged PLGA NPs (Apt-MF-NR-PLGA NPs) to the target cancer cells induced by aptamers was observed using confocal microscopy. Cytotoxicity assay conducted in two cell lines (L929 and MCF-7) confirmed that targeted MCF-7 cancer cells were killed while control cells were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and uptake to the target cancer cells exhibited increased therapeutic effect of the drug. Moreover, these aptamer conjugated magnetic polymer vehicles apart from actively transporting drugs into specifically targeted tumor regions can also be used to induce hyperthermia or for facilitating magnetic guiding of particles to the tumor regions. - Highlights: • Aptamer escorted, theranostic biodegradable PLGA carriers were developed. • Can target cancer cells, control drug release, image and magnetically guide. • Highly specific to the targeted cancer cells thus delivering

  3. pH- and NIR Light-Responsive Polymeric Prodrug Micelles for Hyperthermia-Assisted Site-Specific Chemotherapy to Reverse Drug Resistance in Cancer Treatment.

    Li, Zuhong; Wang, Haibo; Chen, Yangjun; Wang, Yin; Li, Huan; Han, Haijie; Chen, Tingting; Jin, Qiao; Ji, Jian

    2016-05-01

    Despite the exciting advances in cancer chemotherapy over past decades, drug resistance in cancer treatment remains one of the primary reasons for therapeutic failure. IR-780 loaded pH-responsive polymeric prodrug micelles with near infrared (NIR) photothermal effect are developed to circumvent the drug resistance in cancer treatment. The polymeric prodrug micelles are stable in physiological environment, while exhibit fast doxorubicin (DOX) release in acidic condition and significant temperature elevation under NIR laser irradiation. Phosphorylcholine-based biomimetic micellar shell and acid-sensitive drug conjugation endow them with prolonged circulation time and reduced premature drug release during circulation to conduct tumor site-specific chemotherapy. The polymeric prodrug micelles combined with NIR laser irradiation could significantly enhance intracellular DOX accumulation and synergistically induce the cell apoptosis in DOX-resistant MCF-7/ADR cells. Meanwhile, the tumor site-specific chemotherapy combined with hyperthermia effect induces significant inhibition of MCF-7/ADR tumor growth in tumor-bearing mice. These results demonstrate that the well-designed IR-780 loaded polymeric prodrug micelles for hyperthermia-assisted site-specific chemotherapy present an effective approach to reverse drug resistance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. A Parallel 2D Numerical Simulation of Tumor Cells Necrosis by Local Hyperthermia

    Reis, R F; Loureiro, F S; Lobosco, M

    2014-01-01

    Hyperthermia has been widely used in cancer treatment to destroy tumors. The main idea of the hyperthermia is to heat a specific region like a tumor so that above a threshold temperature the tumor cells are destroyed. This can be accomplished by many heat supply techniques and the use of magnetic nanoparticles that generate heat when an alternating magnetic field is applied has emerged as a promise technique. In the present paper, the Pennes bioheat transfer equation is adopted to model the thermal tumor ablation in the context of magnetic nanoparticles. Numerical simulations are carried out considering different injection sites for the nanoparticles in an attempt to achieve better hyperthermia conditions. Explicit finite difference method is employed to solve the equations. However, a large amount of computation is required for this purpose. Therefore, this work also presents an initial attempt to improve performance using OpenMP, a parallel programming API. Experimental results were quite encouraging: speedups around 35 were obtained on a 64-core machine

  5. Synthesis of oleic acid functionalized Fe3O4 magnetic nanoparticles and studying their interaction with tumor cells for potential hyperthermia applications.

    Jadhav, Neena V; Prasad, Amresh I; Kumar, Amit; Mishra, R; Dhara, Sangita; Babu, K R; Prajapat, C L; Misra, N L; Ningthoujam, R S; Pandey, B N; Vatsa, R K

    2013-08-01

    In the present study, oleic acid (OA) functionalized Fe3O4 magnetic nanoparticles (MN) were synthesized following modified wet method of MN synthesis. The optimum amount of OA required for capping of MN and the amount of bound and unbound/free OA was determined by thermogravimetric analysis (TGA). Further, we have studied the effect of water molecules, associated with MN, on the variation in their induction heating ability under alternating current (AC) magnetic field conditions. We have employed a new approach to achieve dispersion of OA functionalized MN (MN-OA) in aqueous medium using sodium carbonate, which improves their biological applicability. Interactions amongst MN, OA and sodium carbonate were studied by Fourier transform infrared spectroscopy (FT-IR). Intracellular localization of MN-OA was studied in mouse fibrosarcoma cells (WEHI-164) by prussian blue staining and confocal laser scanning microscopy (CLSM) using nile blue A as a fluorescent probe. Results showed MN-OA to be interacting mainly with the cell membrane. Their hyperthermic killing ability was evaluated in WEHI-164 cells by trypan blue method. Cells treated with MN-OA in combination with induction heating showed decreased viability as compared to respective induction heating controls. These results were supported by altered cellular morphology after treatment of MN-OA in combination with induction heating. Further, the magnitude of apoptosis was found to be ~5 folds higher in cells treated with MN-OA in combination with induction heating as compared to untreated control. These results suggest the efficacy of MN-OA in killing of tumor cells by cellular hyperthermia. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Drug Delivery Nanoparticles in Skin Cancers

    Dianzani, Chiara; Zara, Gian Paolo; Maina, Giovanni; Pettazzoni, Piergiorgio; Pizzimenti, Stefania; Rossi, Federica; Gigliotti, Casimiro Luca; Ciamporcero, Eric Stefano; Daga, Martina; Barrera, Giuseppina

    2014-01-01

    Nanotechnology involves the engineering of functional systems at nanoscale, thus being attractive for disciplines ranging from materials science to biomedicine. One of the most active research areas of the nanotechnology is nanomedicine, which applies nanotechnology to highly specific medical interventions for prevention, diagnosis, and treatment of diseases, including cancer disease. Over the past two decades, the rapid developments in nanotechnology have allowed the incorporation of multiple therapeutic, sensing, and targeting agents into nanoparticles, for detection, prevention, and treatment of cancer diseases. Nanoparticles offer many advantages as drug carrier systems since they can improve the solubility of poorly water-soluble drugs, modify pharmacokinetics, increase drug half-life by reducing immunogenicity, improve bioavailability, and diminish drug metabolism. They can also enable a tunable release of therapeutic compounds and the simultaneous delivery of two or more drugs for combination therapy. In this review, we discuss the recent advances in the use of different types of nanoparticles for systemic and topical drug delivery in the treatment of skin cancer. In particular, the progress in the treatment with nanocarriers of basal cell carcinoma, squamous cell carcinoma, and melanoma has been reported. PMID:25101298

  7. Nano-magnetite coated with gold: alternative oncological therapy with magnetic hyperthermia; Nanomagnetita recubierta de oro: terapia oncologica alternativa con hipertermia magnetica

    Cordova F, T.; Jimenez G, O.; Basurto I, G. [Universidad de Guanajuato, Campus Leon, Division de Ciencias e Ingenierias, Loma del Bosque 103, Lomas del Campestre, 37150 Leon, Guanajuato (Mexico); Martinez E, J. C., E-mail: theo@fisica.ugto.mx [IPN, Unidad Profesional Interdisciplinaria de Ingenieria Campus Guanajuato, Av. Mineral de Valenciana 200, Industrial Puerto Interior, 36275 Silao de la Victoria, Guanajuato (Mexico)

    2017-10-15

    Localized hyperthermia performed through the use of nanoparticles is one of the most promising procedures for the cancer treatment. In this work, the synthesis of magnetite nanoparticles (Fe{sub 2}O{sub 3}) was carried out using the thermal decomposition method. Subsequently, these nanoparticles were coated with gold and suspended in aqueous phase. As a result, nanoparticles capable of being heated by the application of an alternating magnetic field or through the use of infrared radiation were obtained. As an additional feature, these nanoparticles are biocompatible thanks to their golden coating. The synthesized nanoparticles can be functionalized by the conjugation of a molecule (aptamer, antibody, peptide, etc.) whose target is a cancer cell in order to adhere to it the nanoparticle-marker complex, to subsequently carry out a heating with the objective of induce cell death. In conclusion, the synthesized nanoparticles allow providing an alternative treatment for cancer through the use of localized hyperthermia, either using magnetic or infrared heating. (Author)

  8. An overview of interstitial brachytherapy and hyperthermia

    Brandt, B.B.; Harney, J.

    1989-01-01

    Interstitial thermoradiotherapy, an experimental cancer treatment that combines interstitial radiation implants (brachytherapy) and interstitial hyperthermia, is in the early stages of investigation. In accordance with the procedure used in a current national trial protocol, a 60-minute hyperthermia treatment is administered after catheters are placed into the tumor area while the patient is under general anesthesia. This is immediately followed by loading of radioactive Iridium-192 seeds into the catheters for a defined period of time. Once the prescribed radiation dose is delivered, the radioactive sources are removed and a second, 60-minute hyperthermia treatment is administered. Clinical trials with hyperthermia in combination with radiation have increased in recent years. Nurses caring for these patients need to become more knowledgeable about this investigational therapy. This paper provides an overview of the biologic rationale for this therapy, as well as a description of the delivery method and clinical application. Specific related nursing interventions are defined in a nursing protocol.23 references

  9. Hyperthermia and chemotherapy agent

    Roizin-Towle, L.; Hall, E.J.

    1981-01-01

    The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

  10. A smart magnetic nanoplatform for synergistic anticancer therapy: manoeuvring mussel-inspired functional magnetic nanoparticles for pH responsive anticancer drug delivery and hyperthermia

    Sasikala, Arathyram Ramachandra Kurup; Ghavaminejad, Amin; Unnithan, Afeesh Rajan; Thomas, Reju George; Moon, Myeongju; Jeong, Yong Yeon; Park, Chan Hee; Kim, Cheol Sang

    2015-10-01

    We report the versatile design of a smart nanoplatform for thermo-chemotherapy treatment of cancer. For the first time in the literature, our design takes advantage of the outstanding properties of mussel-inspired multiple catecholic groups - presenting a unique copolymer poly(2-hydroxyethyl methacrylate-co-dopamine methacrylamide) p(HEMA-co-DMA) to surface functionalize the superparamagnetic iron oxide nanoparticles as well as to conjugate borate containing anticancer drug bortezomib (BTZ) in a pH-dependent manner for the synergistic anticancer treatment. The unique multiple anchoring groups can be used to substantially improve the affinity of the ligands to the surfaces of the nanoparticles to form ultrastable iron oxide nanoparticles with control over their hydrodynamic diameter and interfacial chemistry. Thus the BTZ-incorporated-bio-inspired-smart magnetic nanoplatform will act as a hyperthermic agent that delivers heat when an alternating magnetic field is applied while the BTZ-bound catechol moieties act as chemotherapeutic agents in a cancer environment by providing pH-dependent drug release for the synergistic thermo-chemotherapy application. The anticancer efficacy of these bio-inspired multifunctional smart magnetic nanoparticles was tested both in vitro and in vivo and found that these unique magnetic nanoplatforms can be established to endow for the next generation of nanomedicine for efficient and safe cancer therapy.We report the versatile design of a smart nanoplatform for thermo-chemotherapy treatment of cancer. For the first time in the literature, our design takes advantage of the outstanding properties of mussel-inspired multiple catecholic groups - presenting a unique copolymer poly(2-hydroxyethyl methacrylate-co-dopamine methacrylamide) p(HEMA-co-DMA) to surface functionalize the superparamagnetic iron oxide nanoparticles as well as to conjugate borate containing anticancer drug bortezomib (BTZ) in a pH-dependent manner for the synergistic

  11. Nanoparticle "Theranostic" Platforms for Applications in Cancer

    Steiner, Jason Michael

    The study and implementation of nanotechnology as applied to biology is making substantial progress toward the expansion of the dialogue between synthetic and biological systems. This dialogue leads to a deeper understanding of the origins, manifestations, and characteristics of biological phenomenon that ultimately will lead to improved methods of diagnosing and treating a variety of pathologies. Perhaps the most prevalent application of this new technology is in the field of cancer research, encompassing an array of diagnostic and therapeutic approaches for in vivo utilization. These approaches include novel ways of enhancing tumor imaging for earlier detection or delivering toxic therapeutics directly to the site of action, sparing the systemic damage that so often accompanies cancer treatment. However, it is the combination of these essential and orthogonal functionalities that is the hallmark of the promise of nanotechnology. Such materials, coined as "theranostics" for their therapeutic and diagnostic capabilities, allow for a new depth of understanding of the behavior of nanoparticles in vivo, and in particular their efficacy as therapeutic treatments. This dissertation discusses the development of platforms and materials that may be employed as theranostic cancer agents from two distinct philosophical approaches---what may be called "traditional" and "non-traditional" nanotechnology. The "non-traditional" approach details the development of a novel DNA nanoparticle platform created through an exponential enrichment process for selected cell targeting. The products compose a novel class of nanoparticles that possess all of the naturally advantageous properties of DNA. The remainder of the dissertation presents a more "traditional" approach to hierarchical nanoparticle construction, discussing synthesis, stabilization and functionalization of theranostic materials of iron oxide and gold and their combination into novel nanostructures for more efficacious in

  12. Radionuclide investigations of the hormonal reflection of warm stress in cancer patients under whole body guided hyperthermia. Radionuklidnye issledovaniya gormonal'nykh proyavlenij teplovogo stressa u onkologicheskikh bol'nykh pri obshchej upravlyaemoj gipertermii

    Prokhorova, V I; Zhavrid, Eh A; Fradkin, S Z; Tsyrus' , T P; Shitikov, B D; Kosheleva, M I

    1991-01-01

    The results of the radioimmunoassay of ACTH, ST, hydrocortisone, glucagon, C-peptide, insulin and cyclic nucleotides in 180 patients with advanced and metastatic melanomas, soft tissue sarcomas, lung cancers and renal cell carcinomas testify to the development of the syndrome of endocrine hyperfunction in patients under whole-body guided hyperthermia and artificial hyperglycemia as well as of functional pancreas insufficiency. The data presented form a biochemical basis for working out measures to optimally carry out whole-body hyperthermia and artificial hyperglycemia treatment, aimed at increasing the range of indications for its use in clinical oncology.

  13. Towards a versatile platform based on magnetic nanoparticles for in ...

    Magnetic nanoparticles have attracted wide attention because of their usefulness as contrast agents for magnetic resonance imaging (MRI) or colloidal mediators for cancer magnetic hyperthermia. This paper examines these in vivo applications through an understanding of the problems involved and the current and future ...

  14. Modelling Nanoparticle Diffusion into Cancer Tumors

    Podduturi, Vishwa Priya; Derosa, Pedro

    2011-03-01

    Cancer is one of the major, potentially deadly diseases and has been for years. Non-specific delivery of the drug can damage healthy tissue seriously affecting in many cases the patient's living condition. Nanoparticles are being used for a targeted drug delivery thereby reducing the dose. In addition, metallic nanoparticles are being used in thermal treatment of cancer cells where nanoparticles help concentrate heat in the tumor and away from living tissue. We proposed a model that combines random walk with diffusion principles. The particle drift velocity is taken from the Hagen-Poiseuille equation and the velocity profile of the particle at the pores in the capillary wall is obtained using the Coventorware software. Pressure gradient and concentration gradient through the capillary wall are considered. Simulations are performed in Matlab using the Monte Carlo technique. Number of particles leaving the blood vessel through a pore is obtained as a function of blood pressure, the osmotic pressure, temperature, particle concentration, blood vessel radius, and pore size, and the relative effect of each of the parameters is discussed.

  15. Thermosensitive polymer-grafted iron oxide nanoparticles studied by in situ dynamic light backscattering under magnetic hyperthermia

    Hemery, Gauvin; Garanger, Elisabeth; Lecommandoux, Sébastien; Wong, Andrew D.; Gillies, Elizabeth R.; Pedrono, Boris; Bayle, Thomas; Jacob, David; Sandre, Olivier

    2015-12-01

    Thermometry at the nanoscale is an emerging area fostered by intensive research on nanoparticles (NPs) that are capable of converting electromagnetic waves into heat. Recent results suggest that stationary gradients can be maintained between the surface of NPs and the bulk solvent, a phenomenon sometimes referred to as ‘cold hyperthermia’. However, the measurement of such highly localized temperatures is particularly challenging. We describe here a new approach to probing the temperature at the surface of iron oxide NPs and enhancing the understanding of this phenomenon. This approach involves the grafting of thermosensitive polymer chains to the NP surface followed by the measurement of macroscopic properties of the resulting NP suspension and comparison to a calibration curve built up by macroscopic heating. Superparamagnetic iron oxide NPs were prepared by the coprecipitation of ferrous and ferric salts and functionalized with amines, then azides using a sol-gel route followed by a dehydrative coupling reaction. Thermosensitive poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) with an alkyne end-group was synthesized by controlled radical polymerization and was grafted using a copper assisted azide-alkyne cycloaddition reaction. Measurement of the colloidal properties by dynamic light scattering (DLS) indicated that the thermosensitive NPs exhibited changes in their Zeta potential and hydrodynamic diameter as a function of pH and temperature due to the grafted PDMAEMA chains. These changes were accompanied by changes in the relaxivities of the NPs, suggesting application as thermosensitive contrast agents for magnetic resonance imaging (MRI). In addition, a new fibre-based backscattering setup enabled positioning of the DLS remote-head as close as possible to the coil of a magnetic heating inductor to afford in situ probing of the backscattered light intensity, hydrodynamic diameter, and temperature. This approach provides a promising platform for

  16. Magnetic nanoparticle-based cancer nanodiagnostics

    Yousaf Muhammad Zubair; Yu Jing; Hou Yang-Long; Gao Song

    2013-01-01

    Diagnosis facilitates the discovery of an impending disease. A complete and accurate treatment of cancer depends heavily on its early medical diagnosis. Cancer, one of the most fatal diseases world-wide, consistently affects a larger number of patients each year. Magnetism, a physical property arising from the motion of electrical charges, which causes attraction and repulsion between objects and does not involve radiation, has been under intense investigation for several years. Magnetic materials show great promise in the application of image contrast enhancement to accurately image and diagnose cancer. Chelating gadolinium (Gd III) and magnetic nanoparticles (MNPs) have the prospect to pave the way for diagnosis, operative management, and adjuvant therapy of different kinds of cancers. The potential of MNP-based magnetic resonance (MR) contrast agents (CAs) now makes it possible to image portions of a tumor in parts of the body that would be unclear with the conventional magnetic resonance imaging (MRI). Multiple functionalities like variety of targeting ligands and image contrast enhancement have recently been added to the MNPs. Keeping aside the additional complexities in synthetic steps, costs, more convoluted behavior, and effects in-vivo, multifunctional MNPs still face great regulatory hurdles before clinical availability for cancer patients. The trade-off between additional functionality and complexity is a subject of ongoing debate. The recent progress regarding the types, design, synthesis, morphology, characterization, modification, and the in-vivo and in-vitro uses of different MRI contrast agents, including MNPs, to diagnose cancer will be the focus of this review. As our knowledge of MNPs' characteristics and applications expands, their role in the future management of cancer patients will become very important. Current hurdles are also discussed, along with future prospects of MNPs as the savior of cancer victims. (topical review - magnetism

  17. Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

    Yu, Mi Kyung; Park, Jinho; Jon, Sangyong

    2012-01-01

    Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications. PMID:22272217

  18. Study on intraoperative radiotherapy applying hyperthermia together with radiation sensitizers for progressive local carcinoma

    Abe, M; Takahashi, M; Ono, K; Hiraoka, M [Kyoto Univ. (Japan). Faculty of Medicine

    1980-08-01

    Intraoperative radiotherapy for gastric cancer, colonic cancer, pancreatic cancer, cancer of the biliary tract, prostatic carcinoma, cerebral tumor, tumor of soft tissues, and osteosarcoma and its clinical results were described. Basic and clinical studies on effects of both hyperthermia and radiation sensitizers to elevate radiation sensitivity were also described, because effects of intraoperative radiotherapy were raised by applying hyperthermia and hypoxic cell sensitizers.

  19. Hyperthermia for treating cancer

    ... and neck Brain Lung Esophagus Endometrial Breast Bladder Rectal Liver Kidney Cervical Mesothelioma Sarcomas (soft tissues) Melanoma ... Copyright 1997-2018, A.D.A.M., Inc. Duplication for commercial use must be authorized in writing ...

  20. Hyperthermia treatment planning

    Lagendijk, J.J.W.

    2000-01-01

    The development of hyperthermia, the treatment of tumours with elevated temperatures in the range of 40-44 deg. C with treatment times over 30 min, greatly benefits from the development of hyperthermia treatment planning. This review briefly describes the state of the art in hyperthermia technology, followed by an overview of the developments in hyperthermia treatment planning. It particularly highlights the significant problems encountered with heating realistic tissue volumes and shows how treatment planning can help in designing better heating technology. Hyperthermia treatment planning will ultimately provide information about the actual temperature distributions obtained and thus the tumour control probabilities to be expected. This will improve our understanding of the present clinical results of thermoradiotherapy and thermochemotherapy, and will greatly help both in optimizing clinical heating technology and in designing optimal clinical trials. (author)

  1. Selenium nanoparticles: potential in cancer gene and drug delivery.

    Maiyo, Fiona; Singh, Moganavelli

    2017-05-01

    In recent decades, colloidal selenium nanoparticles have emerged as exceptional selenium species with reported chemopreventative and therapeutic properties. This has sparked widespread interest in their use as a carrier of therapeutic agents with results displaying synergistic effects of selenium with its therapeutic cargo and improved anticancer activity. Functionalization remains a critical step in selenium nanoparticles' development for application in gene or drug delivery. In this review, we highlight recent developments in the synthesis and functionalization strategies of selenium nanoparticles used in cancer drug and gene delivery systems. We also provide an update of recent preclinical studies utilizing selenium nanoparticles in cancer therapeutics.

  2. Hyaluronan and calcium carbonate hybrid nanoparticles for colorectal cancer chemotherapy

    Bai, Jinghui; Xu, Jian; Zhao, Jian; Zhang, Rui

    2017-09-01

    A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan-CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan-CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan-CC/Adr nanoparticles. On the other hand, we also found that hyaluronan-CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan-CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.

  3. Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells

    Filippo Cellai

    2017-04-01

    Full Text Available Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosylpyrimido[1,2-α]purin-10(3H-one deoxyguanosine (M1dG and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe3O4-nanoparticles (NPs versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF of 186 kHz using 32P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe3O4-NPs. Significant dose–response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.

  4. Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells.

    Cellai, Filippo; Munnia, Armelle; Viti, Jessica; Doumett, Saer; Ravagli, Costanza; Ceni, Elisabetta; Mello, Tommaso; Polvani, Simone; Giese, Roger W; Baldi, Giovanni; Galli, Andrea; Peluso, Marco E M

    2017-04-29

    Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3 H )-one deoxyguanosine (M₁dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe₃O₄-nanoparticles (NPs) versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF) of 186 kHz using 32 P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe₃O₄-NPs. Significant dose-response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.

  5. Pifithrin-μ, an inhibitor of heat-shock protein 70, can increase the antitumor effects of hyperthermia against human prostate cancer cells.

    Kazumasa Sekihara

    Full Text Available Hyperthermia (HT improves the efficacy of anti-cancer radiotherapy and chemotherapy. However, HT also inevitably evokes stress responses and increases the expression of heat-shock proteins (HSPs in cancer cells. Among the HSPs, HSP70 is known as a pro-survival protein. In this study, we investigated the sensitizing effect of pifithrin (PFT-μ, a small molecule inhibitor of HSP70, when three human prostate cancer cell lines (LNCaP, PC-3, and DU-145 were treated with HT (43°C for 2 h. All cell lines constitutively expressed HSP70, and HT further increased its expression in LNCaP and DU-145. Knockdown of HSP70 with RNA interference decreased the viability and colony-forming ability of cancer cells. PFT-μ decreased the viabilities of all cell lines at one-tenth the dose of Quercetin, a well-known HSP inhibitor. The combination therapy with suboptimal doses of PFT-μ and HT decreased the viability of cancer cells most effectively when PFT-μ was added immediately before HT, and this combination effect was abolished by pre-knockdown of HSP70, suggesting that the effect was mediated via HSP70 inhibition. The combination therapy induced cell death, partially caspase-dependent, and decreased proliferating cancer cells, with decreased expression of c-Myc and cyclin D1 and increased expression of p21(WAF1/Cip, indicating arrest of cell growth. Additionally, the combination therapy significantly decreased the colony-forming ability of cancer cells compared to therapy with either alone. Furthermore, in a xenograft mouse model, the combination therapy significantly inhibited PC-3 tumor growth. These findings suggest that PFT-μ can effectively enhance HT-induced antitumor effects via HSP70 inhibition by inducing cell death and arrest of cell growth, and that PFT-μ is a promising agent for use in combination with HT to treat prostate cancer.

  6. Inhibition of heat-shock protein 90 sensitizes liver cancer stem-like cells to magnetic hyperthermia and enhances anti-tumor effect on hepatocellular carcinoma-burdened nude mice

    Yang, Rui; Tang, Qiusha; Miao, Fengqin; An, Yanli; Li, Mengfei; Han, Yong; Wang, Xihui; Wang, Juan; Liu, Peidang; Chen, Rong

    2015-01-01

    Purpose To explore the thermoresistance and expression of heat-shock protein 90 (HSP90) in magnetic hyperthermia-treated human liver cancer stem-like cells (LCSCs) and the effects of a heat-shock protein HSP90 inhibitor 17-allylamino-17-demethoxgeldanamycin (17-AAG) on hepatocellular carcinoma-burdened nude mice. Methods CD90+ LCSCs were isolated by magnetic-activated cell sorting from BEL-7404. Spheroid formation, proliferation, differentiation, drug resistance, and tumor formation assays were performed to identify stem cell characteristics. CD90-targeted thermosensitive magnetoliposomes (TMs)-encapsulated 17-AAG (CD90@17-AAG/TMs) was prepared by reverse-phase evaporation and its characteristics were studied. Heat tolerance in CD90+ LCSCs and the effect of CD90@17-AAG/TMs-mediated heat sensitivity were examined in vitro and in vivo. Results CD90+ LCSCs showed significant stem cell-like properties. The 17-AAG/TMs were successfully prepared and were spherical in shape with an average size of 128.9±7.7 nm. When exposed to magnetic hyperthermia, HSP90 was up-regulated in CD90+ LCSCs. CD90@17-AAG/TMs inhibited the activity of HSP90 and increased the sensitivity of CD90+ LCSCs to magnetic hyperthermia. Conclusion The inhibition of HSP90 could sensitize CD90+ LCSCs to magnetic hyperthermia and enhance its anti-tumor effects in vitro and in vivo. PMID:26677324

  7. Examination of the magnetic hyperthermia and other magnetic properties of CoFe2O4@MgFe2O4 nanoparticles using external field Mössbauer spectroscopy

    Park, Jeongho; Choi, Hyunkyung; Kim, Sam Jin; Kim, Chul Sung

    2018-05-01

    CoFe2O4@MgFe2O4 core/shell nanoparticles were synthesized by high temperature thermal decomposition with seed-mediated growth. The crystal structure and magnetic properties of the nanoparticles were investigated using X-ray diffractometry (XRD), vibrating sample magnetometry (VSM), and Mössbauer spectrometry. The magnetic hyperthermia properties were investigated using a MagneTherm device. Analysis of the XRD patterns showed that CoFe2O4@MgFe2O4 had a cubic spinel crystal structure with space group Fd-3m and a lattice constant (a0) of 8.3686 Å. The size and morphology of the CoFe2O4@MgFe2O4 nanoparticles were confirmed by HR-TEM. The VSM measurements showed that the saturation magnetization (MS) of CoFe2O4@MgFe2O4 was 77.9 emu/g. The self-heating temperature of CoFe2O4@MgFe2O4 was 37.8 °C at 112 kHz and 250 Oe. The CoFe2O4@MgFe2O4 core/shell nanoparticles showed the largest saturation magnetization value, while their magnetic hyperthermia properties were between those of the CoFe2O4 and MgFe2O4 nanoparticles. In order to investigate the hyperfine interactions of CoFe2O4, MgFe2O4, and CoFe2O4@MgFe2O4, we performed Mössbauer spectrometry at various temperatures. In addition, Mössbauer spectrometry of CoFe2O4@MgFe2O4 was performed at 4.2 K with applied fields of 0-4.5 T, and the results were analyzed with sextets for the tetrahedral A-site and sextets for the octahedral B-site.

  8. Composite magnetic nanoparticles: Synthesis and cancer-related applications

    Cai Ping; Chen Hong-Min; Xie Jin

    2014-01-01

    Recent advances in the preparation and applications of composite magnetic nanoparticles are reviewed and summarized, with a focus on cancer-related applications. (topical review - magnetism, magnetic materials, and interdisciplinary research)

  9. Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

    Wilfred Ngwa

    2017-09-01

    Full Text Available Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH (air versus traditional intravenous (“sea” routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

  10. Targeting of porous hybrid silica nanoparticles to cancer cells

    Rosenholm, J.M.; Meinander, A.; Peuhu, E.; Niemi, R.; Eriksson, J.E.; Sahlgren, C.; Lindén, M.

    2009-01-01

    Mesoporous silica nanoparticles functionalized by surface hyperbranching polymerization of polyethylene imine), PEI, were further modified by introducing both fluorescent and targeting moieties, with the aim of specifically targeting cancer cells. Owing to the high abundance of folate receptors in

  11. Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

    Ngwa, Wilfred; Kumar, Rajiv; Moreau, Michele; Dabney, Raymond; Herman, Allen

    2017-01-01

    Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones) can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous (“sea”) routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects. PMID:28971063

  12. Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids.

    Ngwa, Wilfred; Kumar, Rajiv; Moreau, Michele; Dabney, Raymond; Herman, Allen

    2017-01-01

    Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones) can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous ("sea") routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

  13. Functionalized upconversion nanoparticles for cancer imaging and therapy

    Liu, K.

    2014-01-01

    Near infrared (NIR) light administrated fluorescence imaging and photodynamic therapy (PDT) have shown great promising in cancer diagnosis and treatment. Especially with the recent development of the rare earth ions doped upconversion nanoparticles (UCNPs), much attentions have been attracted in

  14. Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

    Paula, Leonardo B. de; Primo, Fernando L.; Pinto, Marcelo R.; Morais, Paulo C.

    2015-01-01

    The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×10 13 or 1.50×10 13 particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×10 13 or 1.50×10 13 magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments. - Highlights: • Current protocols in nanotechnology allow for biocompatible magnetic nanoparticles being associated with photosensitizer photoactive drugs, which could lead to perfectly controlled drug release. • The combination of the HPT and PDT therapies can be useful to develop further protocols for both advanced in vitro and in vivo assays. • Magnetic nanodevices associated with therapies have led to the decreased of proliferation of cell population that provides a favorable environment for tumor progression

  15. Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

    Paula, Leonardo B. de [Departamento de Química, Centro de Nanotecnologia e Engenharia Tecidual, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901 (Brazil); Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14049-900 (Brazil); Primo, Fernando L. [Departamento de Química, Centro de Nanotecnologia e Engenharia Tecidual, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901 (Brazil); Nanophoton Company, SUPERA Innovation and Technology Park, Av. Doutora Nadir de Aguiar, 1805, Universidade de São Paulo, Ribeirão Preto, P 14056-680 (Brazil); Pinto, Marcelo R. [Departamento de Química, Laboratório de Enzimologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP 14040-901 (Brazil); Morais, Paulo C. [Instituto de Física, Universidade de Brasília, Brasília, DF 70910-900 (Brazil); School of Automation, Huazhong University of Science and Technology, Wuhan 430074 (China); and others

    2015-04-15

    The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×10{sup 13} or 1.50×10{sup 13} particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×10{sup 13} or 1.50×10{sup 13} magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments. - Highlights: • Current protocols in nanotechnology allow for biocompatible magnetic nanoparticles being associated with photosensitizer photoactive drugs, which could lead to perfectly controlled drug release. • The combination of the HPT and PDT therapies can be useful to develop further protocols for both advanced in vitro and in vivo assays. • Magnetic nanodevices associated with therapies have led to the decreased of proliferation of cell population that provides a favorable environment for tumor progression.

  16. Nanosized As2O3/Fe2O3 complexes combined with magnetic fluid hyperthermia selectively target liver cancer cells.

    Wang, Zi-Yu; Song, Jian; Zhang, Dong-Sheng

    2009-06-28

    To study the methods of preparing the magnetic nano-microspheres of Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complexes and their therapeutic effects with magnetic fluid hyperthermia (MFH). Nanospheres were prepared by chemical co-precipitation and their shape and diameter were observed. Hemolysis, micronucleus, cell viability, and LD(50) along with other in vivo tests were performed to evaluate the Fe(2)O(3) microsphere biocompatibility. The inhibition ratio of tumors after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) injections combined with induced hyperthermia in xenograft human hepatocarcinoma was calculated. Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) particles were round with an average diameter of 20 nm and 100 nm as observed under transmission electron microscope. Upon exposure to an alternating magnetic field (AMF), the temperature of the suspension of magnetic particles increased to 41-51 degrees C, depending on different particle concentrations, and remained stable thereafter. Nanosized Fe(2)O(3) microspheres are a new kind of biomaterial without cytotoxic effects. The LD(50) of both Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) in mice was higher than 5 g/kg. One to four weeks after Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complex injections into healthy pig livers, no significant differences were found in serum AST, ALT, BUN and Cr levels among the pigs of all groups (P > 0.05), and no obvious pathological alterations were observed. After exposure to alternating magnetic fields, the inhibition ratio of the tumors was significantly different from controls in the Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) groups (68.74% and 82.79%, respectively; P < 0.01). Tumors of mice in treatment groups showed obvious necrosis, while normal tissues adjoining the tumor and internal organs did not. Fe(2)O(3) and As(2)O(3)/Fe(2)O(3) complexes exerted radiofrequency-induced hyperthermia and drug toxicity on tumors without any liver or kidney damage. Therefore, nanospheres are ideal carriers for tumor-targeted therapy.

  17. Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells

    Song, Xinxin; Kim, Seog-Young; Lee, Yong J.

    2013-01-01

    Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. PMID:24013390

  18. Magnetic nanoparticles for targeted therapeutic gene delivery and magnetic-inducing heating on hepatoma

    Yuan, Chenyan; Zhang, Jia; Li, Hongbo; Zhang, Hao; Wang, Ling; Zhang, Dongsheng; An, Yanli

    2014-01-01

    Gene therapy holds great promise for treating cancers, but their clinical applications are being hampered due to uncontrolled gene delivery and expression. To develop a targeted, safe and efficient tumor therapy system, we constructed a tissue-specific suicide gene delivery system by using magnetic nanoparticles (MNPs) as carriers for the combination of gene therapy and hyperthermia on hepatoma. The suicide gene was hepatoma-targeted and hypoxia-enhanced, and the MNPs possessed the ability to elevate temperature to the effective range for tumor hyperthermia as imposed on an alternating magnetic field (AMF). The tumoricidal effects of targeted gene therapy associated with hyperthermia were evaluated in vitro and in vivo. The experiment demonstrated that hyperthermia combined with a targeted gene therapy system proffer an effective tool for tumor therapy with high selectivity and the synergistic effect of hepatoma suppression. (paper)

  19. Radiosensitizing Silica Nanoparticles Encapsulating Docetaxel for Treatment of Prostate Cancer.

    Belz, Jodi; Castilla-Ojo, Noelle; Sridhar, Srinivas; Kumar, Rajiv

    2017-01-01

    The applications of nanoparticles in oncology include enhanced drug delivery, efficient tumor targeting, treatment monitoring, and diagnostics. The "theranostic properties" associated with nanoparticles have shown enhanced delivery of chemotherapeutic drugs with superior imaging capabilities and minimal toxicities. In conventional chemotherapy, only a fraction of the administered drug reaches the tumor site or cancer cells. For successful translation of these formulations, it is imperative to evaluate the design and properties of these nanoparticles. Here, we describe the design of ultra-small silica nanoparticles to encapsulate a radiosensitizing drug for combined chemoradiation therapy. The small size of nanoparticles allows for better dispersion and uptake of the drug within the highly vascularized tumor tissue. Silica nanoparticles are synthesized using an oil-in-water microemulsion method. The microemulsion method provides a robust synthetic route in which the inner hydrophobic core is used to encapsulate chemotherapy drug, docetaxel while the outer hydrophilic region provides dispersibility of the synthesized nanoparticles in an aqueous environment. Docetaxel is commonly used for treatment of resistant or metastatic prostate cancer, and is known to have radiosensitizing properties. Here, we describe a systematic approach for synthesizing these theranostic nanoparticles for application in prostate cancer.

  20. Using Nanoparticles in Medicine for Liver Cancer Imaging

    Farideh Farokhi Moghadam

    2017-07-01

    Full Text Available One of the most important types of liver cancer is hepatocellular carcinoma (HCC. HCC is the fifth most common cancer, and its correct diagnosis is very important. For the quick diagnosis of HCC, the use of nanoparticles is helpful. The major applications of nanoparticles are in medicine for organ imaging. Two methods of liver imaging are X-ray computed tomography (CT and magnetic resonance imaging (MRI. In this review, we attempt to summarize some of the contrast agents used in imaging such as superparamagnetic iron oxide nanoparticles (SPIONs and iron oxide nanoparticles (IONPs, various types of enhanced MRI for the liver, and nanoparticles like gold (AuNPs, which is used to develop novel CT imaging agents.

  1. Trial of radiation therapy combined with hyperthermia

    Takegawa, Y; Fujiwara, K; Oe, J; Nagase, M; Akiyama, H [Tokushima Univ. (Japan). School of Medicine

    1978-08-01

    Nine patients were treated by the combination therapy of external irradiation and hyperthermia, 5 patients with metastatic lesions; two breast cancer, one lung cancer, one malignant melanoma, one vulva cancer, 1 patient with recurrent lesion of skin cancer and 3 patients with bladder cancer. All patients were treated by heating locally (42/sup 0/C, 30 min) followed by external irradiation with 4,000 - 5,000 rad over 4 to 5 weeks. No local recurrence was found in 4 of 9 patients.

  2. Can magneto-plasmonic nanohybrids efficiently combine photothermia with magnetic hyperthermia?

    Espinosa, Ana; Bugnet, Mathieu; Radtke, Guillaume; Neveu, Sophie; Botton, Gianluigi A.; Wilhelm, Claire; Abou-Hassan, Ali

    2015-11-01

    Multifunctional hybrid-design nanomaterials appear to be a promising route to meet the current therapeutics needs required for efficient cancer treatment. Herein, two efficient heat nano-generators were combined into a multifunctional single nanohybrid (a multi-core iron oxide nanoparticle optimized for magnetic hyperthermia, and a gold branched shell with tunable plasmonic properties in the NIR region, for photothermal therapy) which impressively enhanced heat generation, in suspension or in vivo in tumours, opening up exciting new therapeutic perspectives.Multifunctional hybrid-design nanomaterials appear to be a promising route to meet the current therapeutics needs required for efficient cancer treatment. Herein, two efficient heat nano-generators were combined into a multifunctional single nanohybrid (a multi-core iron oxide nanoparticle optimized for magnetic hyperthermia, and a gold branched shell with tunable plasmonic properties in the NIR region, for photothermal therapy) which impressively enhanced heat generation, in suspension or in vivo in tumours, opening up exciting new therapeutic perspectives. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06168g

  3. TH-C-17A-11: Hyperthermia-Driven Immunotherapy Using Non-Invasive Radiowaves

    Serda, R; Savage, D; Corr, S; Curley, S [Baylor College of Medicine, Houston, TX (United States)

    2014-06-15

    Purpose: The sad truth is that cancer is blamed for the death of nearly one in four people in the US. Immunotherapy offers hope for stimulating cancer immunity leading to targeted killing of cancer cells and a preventative measure for cancer recurrence. Unfortunately, the clinical efficacy of immunotherapy has not yet been established, however novel approaches are being developed, including combining immunotherapy with traditional chemotherapy, radiotherapy or thermal therapy. Therapeutics such as radiofrequency (RF) ablation and select chemotherapeutics induce mild anticancer immune responses. This project seeks to enhance the immune responses stimulated by these agents by co-delivery of nanoparticle-based chemotherapeutics and immune modulators in the presence of RF induced hyperthermia. Methods: A 4T1 mouse model of breast cancer is used to test the ability of RF waves to enhance accumulation of nanoparticles in tumor tissue by increasing blood flow and extravation of nanoparticles from hyperpermeable vessels. Images of particle and cell trafficking in the tumor are captured using an integrated RF and confocal imaging system, and tumor growth is monitored by tumor bioluminescence and caliper measurements. Results: Here we demonstrate enhanced intratumoral blood flow induced by non-invasive RF waves and an increase in nanoparticle accumulation in the tumor. IL-12 is shown to have powerful anti-tumor effects leading to tumor regression and the release of Th1-biased cytokines. Doxorubicin nanoparticles combined with adjuvant nanoparticles exhibited superior antitumor effects to single agent therapy. Conclusion: RF therapy combined with nanotherapeutics is a promising approach to enhance the delivery of therapeutics to the tumor and to stimulate a tumor microenvironment that supports the development of cancer-specific immune responses. This research was supported by the National Institute of Health grant numbers U54 CA143837 and U54 CA151668, and the Kanzius

  4. TH-C-17A-11: Hyperthermia-Driven Immunotherapy Using Non-Invasive Radiowaves

    Serda, R; Savage, D; Corr, S; Curley, S

    2014-01-01

    Purpose: The sad truth is that cancer is blamed for the death of nearly one in four people in the US. Immunotherapy offers hope for stimulating cancer immunity leading to targeted killing of cancer cells and a preventative measure for cancer recurrence. Unfortunately, the clinical efficacy of immunotherapy has not yet been established, however novel approaches are being developed, including combining immunotherapy with traditional chemotherapy, radiotherapy or thermal therapy. Therapeutics such as radiofrequency (RF) ablation and select chemotherapeutics induce mild anticancer immune responses. This project seeks to enhance the immune responses stimulated by these agents by co-delivery of nanoparticle-based chemotherapeutics and immune modulators in the presence of RF induced hyperthermia. Methods: A 4T1 mouse model of breast cancer is used to test the ability of RF waves to enhance accumulation of nanoparticles in tumor tissue by increasing blood flow and extravation of nanoparticles from hyperpermeable vessels. Images of particle and cell trafficking in the tumor are captured using an integrated RF and confocal imaging system, and tumor growth is monitored by tumor bioluminescence and caliper measurements. Results: Here we demonstrate enhanced intratumoral blood flow induced by non-invasive RF waves and an increase in nanoparticle accumulation in the tumor. IL-12 is shown to have powerful anti-tumor effects leading to tumor regression and the release of Th1-biased cytokines. Doxorubicin nanoparticles combined with adjuvant nanoparticles exhibited superior antitumor effects to single agent therapy. Conclusion: RF therapy combined with nanotherapeutics is a promising approach to enhance the delivery of therapeutics to the tumor and to stimulate a tumor microenvironment that supports the development of cancer-specific immune responses. This research was supported by the National Institute of Health grant numbers U54 CA143837 and U54 CA151668, and the Kanzius

  5. Magnetic and in vitro heating properties of implants formed in situ from injectable formulations and containing superparamagnetic iron oxide nanoparticles (SPIONs) embedded in silica microparticles for magnetically induced local hyperthermia

    Le Renard, Pol-Edern; Lortz, Rolf; Senatore, Carmine; Rapin, Jean-Philippe; Buchegger, Franz; Petri-Fink, Alke; Hofmann, Heinrich; Doelker, Eric; Jordan, Olivier

    2011-01-01

    The biological and therapeutic responses to hyperthermia, when it is envisaged as an anti-tumor treatment modality, are complex and variable. Heat delivery plays a critical role and is counteracted by more or less efficient body cooling, which is largely mediated by blood flow. In the case of magnetically mediated modality, the delivery of the magnetic particles, most often superparamagnetic iron oxide nanoparticles (SPIONs), is also critically involved. We focus here on the magnetic characterization of two injectable formulations able to gel in situ and entrap silica microparticles embedding SPIONs. These formulations have previously shown suitable syringeability and intratumoral distribution in vivo. The first formulation is based on alginate, and the second on a poly(ethylene-co-vinyl alcohol) (EVAL). Here we investigated the magnetic properties and heating capacities in an alternating magnetic field (141 kHz, 12 mT) for implants with increasing concentrations of magnetic microparticles. We found that the magnetic properties of the magnetic microparticles were preserved using the formulation and in the wet implant at 37 o C, as in vivo. Using two orthogonal methods, a common SLP (20 W g -1 ) was found after weighting by magnetic microparticle fraction, suggesting that both formulations are able to properly carry the magnetic microparticles in situ while preserving their magnetic properties and heating capacities. - Research highlights: → Magnetic formulations that form implants on injection into tissues are proposed for hyperthermia. → Superparamagnetic properties of the SPION-silica composite microparticles are preserved in the wet implants. → Heat-dissipating properties (SLP of 20 W/g of implant) support in vivo use.

  6. The comparative effect of wrapping solid gold nanoparticles and hollow gold nanoparticles with doxorubicin-loaded thermosensitive liposomes for cancer thermo-chemotherapy.

    Li, Yanan; He, Dongsheng; Tu, Jiasheng; Wang, Ru; Zu, Chang; Chen, You; Yang, Wenqian; Shi, Di; Webster, Thomas J; Shen, Yan

    2018-04-26

    Since conventional chemotherapy is a systemic treatment that affects the body globally and will not concentrate inside the tumor, it causes adverse side effects to patients. In this study, doxorubicin (DOX) together with solid gold nanoparticles (GNPs) or hollow gold nanoparticles (HGNPs), respectively, is loaded inside thermosensitive liposomes (GNPs&DOX-TLs and HGNPs&DOX-TLs), where the GNPs and HGNPs act as a "nanoswitch" for killing tumor cells directly by hyperthermia and triggering DOX release from TLs in the tumor quickly by near infrared laser (NIR) illumination. In addition, this study investigated the photothermal transformation ability, NIR triggered drug release behavior, and the intracellular uptake and cytotoxicity of breast tumor cells and the thermo-chemotherapy mediated by the co-delivery of GNPs&DOX-TLs and HGNPs&DOX-TLs. GNPs and HGNPs had very different light-to-heat transduction efficiencies, while the hollow HGNPs had the advantage of NIR surface plasmon tunability, resulting in the photothermal ablation of tumors with 800 nm light penetration in tissue. The prepared HGNPs&DOX-TLs exhibited a spherical shape with a diameter of 190 nm and a ξ potential of -29 mV, which were steadily dispersed for at least one month. The co-encapsulated DOX was released under hyperthermia caused by NIR-responsive HGNPs and the local drug concentration increased along with the disintegration of the liposomal membrane. This co-delivery of HGNPs&DOX-TLs produced a synergistic cytotoxicity response, thereby enhancing anticancer efficacy 8-fold and increasing the survival time compared to GNPs&DOX-TLs. This work suggested that the co-delivery of HGNPs&DOX-TLs followed by burst-release of DOX using NIR-responsive HGNPs sensitized cancer cells to the chemotherapeutic compound, which provided a novel concept for the combination strategy of chemotherapy and photothermal therapy. These results suggest that the markedly improved therapeutic efficacy and decreased systemic

  7. Multifunctional porous silicon nanoparticles for cancer theranostics.

    Wang, Chang-Fang; Sarparanta, Mirkka P; Mäkilä, Ermei M; Hyvönen, Maija L K; Laakkonen, Pirjo M; Salonen, Jarno J; Hirvonen, Jouni T; Airaksinen, Anu J; Santos, Hélder A

    2015-04-01

    Nanomaterials provide a unique platform for the development of theranostic systems that combine diagnostic imaging modalities with a therapeutic payload in a single probe. In this work, dual-labeled iRGD-modified multifunctional porous silicon nanoparticles (PSi NPs) were prepared from dibenzocyclooctyl (DBCO) modified PSi NPs by strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry. Hydrophobic antiangiogenic drug, sorafenib, was loaded into the modified PSi NPs to enhance the drug dissolution rate and improve cancer therapy. Radiolabeling of the developed system with (111)In enabled the monitoring of the in vivo biodistribution of the nanocarrier by single photon emission computed tomography (SPECT) in an ectopic PC3-MM2 mouse xenograft model. Fluorescent labeling with Alexa Fluor 488 was used to determine the long-term biodistribution of the nanocarrier by immunofluorescence at the tissue level ex vivo. Modification of the PSi NPs with an iRGD peptide enhanced the tumor uptake of the NPs when administered intravenously. After intratumoral delivery the NPs were retained in the tumor, resulting in efficient tumor growth suppression with particle-loaded sorafenib compared to the free drug. The presented multifunctional PSi NPs highlight the utility of constructing a theranostic nanosystems for simultaneous investigations of the in vivo behavior of the nanocarriers and their drug delivery efficiency, facilitating the selection of the most promising materials for further NP development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Radiosensitizing Silica Nanoparticles encapsulating Docetaxel for Treatment of Prostate Cancer

    Belz, Jodi; Castilla-Ojo, Noelle; Sridhar, Srinivas; Kumar, Rajiv

    2017-01-01

    The applications of nanoparticles in oncology include enhanced drug delivery, efficient tumor targeting, treatment monitoring and diagnostics. The ‘theranostic properties’ associated with nanoparticles have shown enhanced delivery of chemotherapeutic drugs with superior imaging capabilities and minimal toxicities. In conventional chemotherapy, only a fraction of the administered drug reaches the tumor site or cancer cells. For successful translation of these formulations, it is imperative to ...

  9. Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability

    Luo, Haitao; Jiang, Bingbing; Li, Bingyun; Li, Zhaoliang; Jiang, Bing-Hua; Chen, Yi Charlie

    2012-01-01

    Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles resulted in enhanced reduction of cancer cell viability. Among the nonionic polymeric nanoparticles, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nanoparticles incorporating kaempferol led to significant reduction in cell viability of both cancerous and normal cells. Poly(DL-lactic acid-co-glycolic acid) (PLGA) nanoparticles incorporating kaempferol resulted in enhanced reduction of cancer cell viability together with no significant reduction in cell viability of normal cells compared with kaempferol alone. Therefore, both PEO-PPO-PEO and PLGA nanoparticle formulations were effective in reducing cancer cell viability, while PLGA nanoparticles incorporating kaempferol had selective toxicity against cancer cells and normal cells. A PLGA nanoparticle formulation could be advantageous in the prevention and treatment of ovarian cancers. On the other hand, PEO-PPO-PEO nanoparticles incorporating kaempferol were more effective inhibitors of cancer cells, but they also significantly reduced the viability of normal cells. PEO-PPO-PEO nanoparticles incorporating kaempferol may be suitable as a cancer-targeting strategy, which could limit the effects of the nanoparticles on normal cells while retaining their potency against cancer cells. We

  10. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    Warangkana Lohcharoenkal

    2014-01-01

    Full Text Available Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

  11. Multifunctional nanoparticle developments in cancer diagnosis and treatment

    Sepideh Parvanian

    2017-04-01

    Full Text Available Nanotechnology, although still in the early stages, has the potential to revolutionize the early diagnosis, treatment, and monitoring of disease progression. Technological application of nanometer molecules in medicine with the aim of fighting and curing ailments is the globally definition of nanomedicine. The success of nanotechnology in the healthcare part is driven by the possibility to work at the same scale of several biological processes, cellular mechanisms, and organic molecules. With the growing understanding of methods to functionalize nanoparticles and the continued efforts of creative scientists to advance this technology, it is likely that functionalized nanoparticles will become an important tool in the above mentioned areas. This paper describes the role of multifunctional nanoparticle in diagnosis and treatment of cancer. Therefore, the aim of this review is to provide basic information on nanoparticles, describe previously developed methods to functionalize nanoparticles and discuss their potential applications in biomedical sciences and finally mention the therapeutic nanoparticle commercialization challenges. Keywords: Multifunctional nanoparticle, Cancer, Diagnosis, Treatment, Therapy

  12. Protein nanoparticles as drug delivery carriers for cancer therapy.

    Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie; Rojanasakul, Yon

    2014-01-01

    Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

  13. Oligonucleotide-based theranostic nanoparticles in cancer therapy

    Shahbazi, Reza; Ozpolat, Bulent; Ulubayram, Kezban

    2016-01-01

    Theranostic approaches, combining the functionality of both therapy and imaging, have shown potential in cancer nanomedicine. Oligonucleotides such as small interfering RNA and microRNA, which are powerful therapeutic agents, have been effectively employed in theranostic systems against various cancers. Nanoparticles are used to deliver oligonucleotides into tumors by passive or active targeting while protecting the oligonucleotides from nucleases in the extracellular environment. The use of quantum dots, iron oxide nanoparticles and gold nanoparticles and tagging with contrast agents, like fluorescent dyes, optical or magnetic agents and various radioisotopes, has facilitated early detection of tumors and evaluation of therapeutic efficacy. In this article, we review the advantages of theranostic applications in cancer therapy and imaging, with special attention to oligonucleotide-based therapeutics. PMID:27102380

  14. Emerging applications of nanoparticles for lung cancer diagnosis and therapy

    Sukumar, Uday Kumar; Bhushan, Bharat; Dubey, Poornima; Matai, Ishita; Sachdev, Abhay; Packirisamy, Gopinath

    2013-07-01

    Lung cancer is by far the leading cause of cancer-related mortality worldwide, most of them being active tobacco smokers. Non small cell lung cancer accounts for around 85% to 90% of deaths, whereas the rest is contributed by small cell lung cancer. The extreme lethality of lung cancer arises due to lack of suitable diagnostic procedures for early detection of lung cancer and ineffective conventional therapeutic strategies. In course with desperate attempts to address these issues independently, a multifunctional nanotherapeutic or diagnostic system is being sought as a favorable solution. The manifestation of physiochemical properties of such nanoscale systems is tuned favorably to come up with a versatile cancer cell targeted diagnostic and therapeutic system. Apart from this, the aspect of being at nanoscale by itself confers the system with an advantage of passive accumulation at the site of tumor. This review provides a broad perspective of three major subclasses of such nanoscale therapeutic and diagnostic systems which include polymeric nanoparticles-based approaches, metal nanoparticles-based approaches, and bio-nanoparticles-based approaches. This review work also serves the purpose of gaining an insight into the pros and cons of each of these approaches with a prospective improvement in lung cancer therapeutics and diagnostics.

  15. Advances in targeting strategies for nanoparticles in cancer imaging and therapy.

    Yhee, Ji Young; Lee, Sangmin; Kim, Kwangmeyung

    2014-11-21

    In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

  16. Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls

    Lee, Jihyoun; Chatterjee, Dev Kumar; Lee, Min Hyuk; Krishnan, Sunil

    2014-01-01

    Despite remarkable achievements in the treatment of breast cancer, some obstacles still remain. Gold nanoparticles may prove valuable in addressing these problems owing to their unique characteristics, including their enhanced permeability and retention in tumor tissue, their light absorbance and surface plasmon resonance in near-infrared light, their interaction with radiation to generate secondary electrons, and their ability to be conjugated with drugs or other agents. Herein, we discuss some basic concepts of gold nanoparticles, and early results from studies regarding their use in breast cancer, including toxicity and side effects. We also discuss these particles’ potential clinical applications. PMID:24556077

  17. Establishment of a biophysical model to optimize endoscopic targeting of magnetic nanoparticles for cancer treatment.

    Roeth, Anjali A; Slabu, Ioana; Baumann, Martin; Alizai, Patrick H; Schmeding, Maximilian; Guentherodt, Gernot; Schmitz-Rode, Thomas; Neumann, Ulf P

    2017-01-01

    Superparamagnetic iron oxide nanoparticles (SPION) may be used for local tumor treatment by coupling them to a drug and accumulating them locally with magnetic field traps, that is, a combination of permanent magnets and coils. Thereafter, an alternating magnetic field generates heat which may be used to release the thermosensitively bound drug and for hyperthermia. Until today, only superficial tumors can be treated with this method. Our aim was to transfer this method into an endoscopic setting to also reach the majority of tumors located inside the body. To find the ideal endoscopic magnetic field trap, which accumulates the most SPION, we first developed a biophysical model considering anatomical as well as physical conditions. Entities of choice were esophageal and prostate cancer. The magnetic susceptibilities of different porcine and rat tissues were measured with a superconducting quantum interference device. All tissues showed diamagnetic behavior. The evaluation of clinical data (computed tomography scan, endosonography, surgical reports, pathological evaluation) of patients gave insight into the topographical relationship between the tumor and its surroundings. Both were used to establish the biophysical model of the tumors and their surroundings, closely mirroring the clinical situation, in which we could virtually design, place and evaluate different electromagnetic coil configurations to find optimized magnetic field traps for each tumor entity. By simulation, we could show that the efficiency of the magnetic field traps can be enhanced by 38-fold for prostate and 8-fold for esophageal cancer. Therefore, our approach of endoscopic targeting is an improvement of the magnetic drug-targeting setups for SPION tumor therapy as it holds the possibility of reaching tumors inside the body in a minimal-invasive way. Future animal experiments must prove these findings in vivo.

  18. Multifunctional gold nanoparticles for photodynamic therapy of cancer

    Khaing Oo, Maung Kyaw

    As an important and growing branch of photomedicine, photodynamic therapy (PDT) is being increasingly employed in clinical applications particularly for the treatment of skin cancer. This dissertation focuses on the synthesis, characterization and deployment of gold nanoparticles for enhanced PDT of fibrosarcoma cancer cells. We have developed robust strategies and methods in fabrication of gold nanoparticles with positively- and negatively-tethered surface charges by photo-reduction of gold chloride salt using branched polyethyleneimine and sodium citrate respectively. An optimal concentration window of gold salt has been established to yield the most stable and monodispersed gold nanoparticles. 5-aminolevulinic acid (5-ALA), a photosensitizing precursor, has been successfully conjugated on to positively charged gold nanoparticles through electrostatic interactions. The 5-ALA/gold nanoparticle conjugates are biocompatible and have shown to be preferably taken up by cancer cells. Subsequent light irradiation results in the generation of reactive oxygen species (ROS) in cancer cells, leading to their destruction without adverse effects on normal fibroblasts. We have demonstrated for the first time that gold nanoparticles can enhance PDT efficacy by 50% compared to the treatment with 5-ALA alone. Collected evidence has strongly suggested that this enhancement stems from the elevated formation of ROS via the strongly localized electric field of gold nanoparticles. Through single cell imaging using surface-enhanced Raman scattering enabled by the very same gold nanoparticles, we have shown that multifunctionality of gold nanoparticles can be harvested concurrently for biomedical applications in general and for PDT in specific. In other words, gold nanoparticles can be used not only for targeted drug delivery and field-enhanced ROS formation, but also for monitoring cell destructions during PDT. Finally, our COMSOL Multiphysics simulation of the size-dependent electric

  19. Hyperthermia on skin immune system and its application in the treatment of HPV-infected skin diseases

    Gao Xinghua; Chen Hongduo

    2014-01-01

    In this paper, the effects of hyperthermia on cells and immune system are introduced briefly. The mechanism of action of hyperthermia on human papilloma virus (HPV)-infected skin diseases was elaborated as an example in this paper. Many studies have proved that hyperthermia affects a number of cellular and molecu- lar constitutes in the skin immune system, involving both innate and adaptive immune responses; the efficacy of hyperthermia in treating some infectious and cancerous conditions has been validated and applied in clinics, while molecular mechanisms of hyperthermia affecting the immunereaction is still unclear.

  20. Interstitial microwave hyperthermia treatment investigations

    Siauve, N; Lormel, C

    2012-01-01

    Microwave ablation also called interstitial hyperthermia is a medical procedure used in the treatment of many cancers, cardiac arrhythmias and other medical conditions. With this medical therapy, an electromagnetic source (antenna) is directly positioned in the target tissue and a sufficient power is injected to necrosis the tissue. The aim of this study is to propose a design procedure and develop the associated tools, for determining the optimal shape, dimensions, type and operating frequency of antenna according to the target volume. In this context, a 3D numerical predictive model of temperature elevation induced by the electric fields and two benches for thermal and electrical tissues properties characterization have been developed. To validate the procedure and the different tools, an experimental bench test which includes interstitial antenna, external microwave generator, phantom that represents the target tissue and measurement system of temperature and electric field has been elaborated.

  1. Nanoparticles for cancer gene therapy: Recent advances, challenges, and strategies.

    Wang, Kui; Kievit, Forrest M; Zhang, Miqin

    2016-12-01

    Compared to conventional treatments, gene therapy offers a variety of advantages for cancer treatment including high potency and specificity, low off-target toxicity, and delivery of multiple genes that concurrently target cancer tumorigenesis, recurrence, and drug resistance. In the past decades, gene therapy has undergone remarkable progress, and is now poised to become a first line therapy for cancer. Among various gene delivery systems, nanoparticles have attracted much attention because of their desirable characteristics including low toxicity profiles, well-controlled and high gene delivery efficiency, and multi-functionalities. This review provides an overview on gene therapeutics and gene delivery technologies, and highlight recent advances, challenges and insights into the design and the utility of nanoparticles in gene therapy for cancer treatment. Copyright © 2016. Published by Elsevier Ltd.

  2. Mechanisms of hyperthermia induced radiatiosensitization for treatment of human papillomavirus positive tumors

    Oei, Arlene; Leeuwen, Caspar van; Stalpers, Lukas; Rodermond, Hans; Kok, Petra; Crezee, Hans; Franken, Nicolaas

    2016-01-01

    HPV is associated with cervical cancer, the third most common cancer in women. In over 70% of cervical cancers, the high-risk HPV-types 16 and 18 are found. In these tumors, functionality of p53 is suppressed by the presence of protein E6. Hyperthermia is a clinical application of heat in which tumour temperatures are raised to 40-43°C and combined hyperthermia with radiation is very effective in the treatment of cervical cancer

  3. Engineered magnetic core shell nanoprobes: Synthesis and applications to cancer imaging and therapeutics.

    Mandal, Samir; Chaudhuri, Keya

    2016-02-26

    Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.

  4. Rare earth fluorescent nanoparticles for specific cancer cell targeting

    Stefanakis, Dimitrios; Ghanotakis, Demetrios F.

    2016-01-01

    Terbium layered hydroxide nanoparticles (Tb_2(OH)_5NO_3) were synthesized by a one-pot coprecipitation method. The characterization of this preparation revealed highly oriented fluorescent nanoparticles. An attempt to improve the properties of Tb_2(OH)_5NO_3 resulted in the preparation of two optimized nanoparticles. In particular, Tb_2(OH)_5NO_3:Eu and Tb_2(OH)_5NO_3-FA were prepared when Tb_2(OH)_5NO_3 was doped with Europium and when the surface was modified with folic acid (FA), respectively. The size of the above nanoparticles was below 100 nm, and thus they have the potential to be used for biomedical applications. The interaction of nanoparticles with human cells was studied using confocal microscopy. This study revealed that only the nanoparticles modified with folic acid have the ability to be targeted to HeLa cells. This specific identification of cancer cells, in combination with the fluorescent properties of Tb_2(OH)_5NO_3, could render these nanoparticles appropriate for biomedical applications.

  5. Rare earth fluorescent nanoparticles for specific cancer cell targeting

    Stefanakis, Dimitrios; Ghanotakis, Demetrios F., E-mail: ghanotakis@uoc.gr [University of Crete, Department of Chemistry (Greece)

    2016-07-15

    Terbium layered hydroxide nanoparticles (Tb{sub 2}(OH){sub 5}NO{sub 3}) were synthesized by a one-pot coprecipitation method. The characterization of this preparation revealed highly oriented fluorescent nanoparticles. An attempt to improve the properties of Tb{sub 2}(OH){sub 5}NO{sub 3} resulted in the preparation of two optimized nanoparticles. In particular, Tb{sub 2}(OH){sub 5}NO{sub 3}:Eu and Tb{sub 2}(OH){sub 5}NO{sub 3}-FA were prepared when Tb{sub 2}(OH){sub 5}NO{sub 3} was doped with Europium and when the surface was modified with folic acid (FA), respectively. The size of the above nanoparticles was below 100 nm, and thus they have the potential to be used for biomedical applications. The interaction of nanoparticles with human cells was studied using confocal microscopy. This study revealed that only the nanoparticles modified with folic acid have the ability to be targeted to HeLa cells. This specific identification of cancer cells, in combination with the fluorescent properties of Tb{sub 2}(OH){sub 5}NO{sub 3}, could render these nanoparticles appropriate for biomedical applications.

  6. Synthesis of aqueous ferrofluids of ZnxFe3−xO4 nanoparticles by citric acid assisted hydrothermal-reduction route for magnetic hyperthermia applications

    Behdadfar, Behshid; Kermanpur, Ahmad; Sadeghi-Aliabadi, Hojjat; Morales, Maria del Puerto; Mozaffari, Morteza

    2012-01-01

    Superparamagnetic and monodispersed aqueous ferrofluids of Zn substituted magnetite nanoparticles (Zn x Fe 3−x O 4 , x=0, 0.25, 0.3, 0.37 and 0.4) were synthesized via hydrothermal-reduction route in the presence of citric acid, which is a facile, low energy and environmental friendly method. The synthesized nanoparticles were characterized by X ray diffraction (XRD) analysis, Fourier transform infrared (FTIR) spectroscopy, scanning and transmission electron microscopy (SEM and TEM) and the dynamic light scattering (DLS) method. The results showed that a certain amount of citric acid was required to obtain single phase Zn substituted magnetite nanoparticles. Citric acid acted as a modulator and reducing agent in the formation of spinel structure and controlled nanoparticle size and crystallinity. Mean particle sizes of the prepared nanoparticles were around 10 nm. The results that are obtained from XRD, magnetic and power loss measurements showed that the crystallinity, saturation magnetization (M S ) and loss power of the synthesized ferrofluids were all influenced by the substitution of Zn in the structure of magnetite. The Zn substituted magnetite nanoparticles obtained by this route showed a good stability in aqueous medium (pH 7) and hydrodynamic sizes below 100 nm and polydispersity indexes below 0.2. The calculated intrinsic loss power (ILP) for the sample x=0.3 (e.g. 2.36 nH m 2 /kg) was comparable to ILP of commercial ferrofluids with similar hydrodynamic sizes. - Highlights: ► We synthesized Zn substituted magnetite nanoparticles via hydrothermal-reduction route. ► We used citric acid as a reducing agent in this route. ► This route is a facile, low energy and environmental friendly method. ► The nanoparticles obtained by this route were superparamagnetic and stable in water. ► The calculated intrinsic loss power for the sample x=0.3 was 2.36 nH m 2 /kg.

  7. Re: Engineered Nanoparticles Induce Cell Apoptosis: Potential for Cancer Therapy

    Fehmi Narter

    2016-09-01

    Full Text Available Engineered nanoparticles (ENPs have been widely applied in industry, biology and medicine recently (i.e. clothes, sunscreens, cosmetics, foods, diagnostic medicine, imaging and drug delivery. There are many kinds of manufactured nanomaterial products including TiO2, ZnO, CeO2, Fe2O3, and CuO (as metal oxide nanoparticles as well as gold, silver, platinum and palladium (as metal nanoparticles, and other carbon-based ENP’s such as carbon nanotububes and quantum dots. ENPs with their sizes no larger than 100 nm are able to enter the human body and accumulate in organs and cause toxic effects. In many researches, ENP effects on the cancer cells of different organs with related cell apoptosis were noted (AgNP, nano-Cr2O3, Au-Fe2O3 NPs, nano-TiO2, nano-HAP, nano-Se, MoO3 nanoplate, Realgar nanoparticles. ENPs, with their unique properties, such as surface charge, particle size, composition and surface modification with tissue recognition ligands or antibodies, has been increasingly explored as a tool to carry small molecular weight drugs as well as macromolecules for cancer therapy, thus generating the new concept “nanocarrier”. Direct induction of cell apoptosis by ENPs provides an opportunity for cancer treatment. In the century of nanomedicine that depends on development of the nanotechnology, ENPs have a great potential for application in cancer treatment with minimal side effects.

  8. Real-time temperature feedback for nanoparticles based tumor thermal treatment (Conference Presentation)

    Steinberg, Idan; Tamir, Gil; Gannot, Israel

    2017-02-01

    Systemic hyperthermia therapy exploits the fact that cancer cells are more sensitive to elevated temperatures than healthy tissue. Systemic application of hyperthermia externally usually leads to low efficiency treatment. Recently, our group and others have proposed an antibody conjugated magnetic nanoparticles (MNPs) approach to overcome the limitation of systemic hyperthermia. MNPs can bind specifically to the tumor sites, thus delivering internal highly effective targeted hyperthermia. However, such internal mechanism requires more complicated controls and monitoring. This current work presents a deep tissue temperature monitoring method to control hyperthermia effectiveness and minimize collateral damage to surrounding tissues. A low-frequency narrowband modulation of the RF field used for MNP heating leads to the generation of diffused thermal waves which propagate to the tissue surface and captured by a thermal camera. A Fourier domain, analytical heat transfer model is used for temperature monitoring algorithm. The ill-posed thermal inverse problem is solved efficiently by iterating over the source power until both the amplitude and phase match the recorded thermal image sequence. The narrow bandwidth thermal stimulation enables acquiring deep signals with high SNR. We show that thermal transverse resolution improves as the stimulation frequency increases even slightly above DC, enabling better heat source transverse separation and margin identification in the case of distributed tumors. These results can be used as a part of an overall image and treat system for efficient detection of tumors, manipulation of MNPs and monitoring MNP based hyperthermia.

  9. Hyperthermia: clinical results

    Bicher, H.I.

    1982-01-01

    A large number of patients have now been entered into a phase I/II protocol to examine the effects of fractionated hyperthermia and radiation on tumor response. Included in the study were 11 different histologies with anatomical locations varying between peripheral and superficial metastases to deep-seated, solid tumors. Patients were treated with four fractions of microwave-induced hyperthermia (45.0 +- 0.5 0 C), each separated by intervals of 72 hours. Microwaves at frequencies of 915 MHz or 300 MHz were employed, Patients were given a one week rest following the first four treatments, following which a second series of four fractions were administered, again at 72 hour intervals. Each of these fractions consisted of a 400 rad dose of radiation followed within 20 min by hyperthermia (42.5 +- 5 0 C) for 1.5 hours. To date 121 fields have been treated by 82 patients. Total regression is seen in 65% of all cases, partial regression in 35% and no response is seen in only 5% of treatments. Adverse effects were rare. Site specific trials are currently in progress to study the feasibility of deep-seated heating with intracavitary antennae as well as to assess tumor response. In addition, a randomized trial to examine the clinical relevance of thermotolerance has been started

  10. Hyperthermia and radiotherapy

    Dietzel, F.

    1979-01-01

    Of decisive importance for superadditive enhancement is the close temporal correlation of hyperthermia and radiotherapy. It is recommended to first irradiate and then use heat treatment in order to ensure that dividable tumour cells are irradiated before hyperthermia. To achieve an optimal enhancing effect, temperatures of appr. 42 0 are sufficient. In order to be able to neglect temperature regulation and convection effects, hyperthermia for clinical use must be carried out in doses high enough to ensure that it can be finished within 3-4 minutes. It is necessary to make efforts to find out which forms of application can be realised in order to reach deeper tissue regions, thus making possible at least a half-depth-therapy. Up to day, only the 2 cm near to the surface can be heated in a sufficiently homogeneous way. In the FRG, there are more than 200 high-volt-therapy systems, including electron accelerators and telegamma systems. This is a dense network of radiation-therapeutical supply. An improved therapy effect of loose ionising rays which, with the help of the hypertherming, would almost be equal to irradiation with high ionisation density, is not only of scientific interest, but also of high interest for public health. (orig./MG) 891 MG/orig.- 892 RDG [de

  11. γ-Fe{sub 2}O{sub 3} by sol–gel with large nanoparticles size for magnetic hyperthermia application

    Lemine, O.M., E-mail: leminej@yahoo.com [Physics Department, College of Sciences, Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh (Saudi Arabia); Omri, K. [Laboratory of Physics of Materials and Nanomaterials Applied at Environment (LaPhyMNE), Faculty of Sciences in Gabes, Gabes (Tunisia); Iglesias, M.; Velasco, V. [Instituto de Magnetismo Aplicado, UCM-ADIF-CSIC (Spain); Crespo, P.; Presa, P. de la [Instituto de Magnetismo Aplicado, UCM-ADIF-CSIC (Spain); Dpto. Física de Materiales, Universidad Complutense de Madrid (Spain); El Mir, L. [Physics Department, College of Sciences, Al Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh (Saudi Arabia); Laboratory of Physics of Materials and Nanomaterials Applied at Environment (LaPhyMNE), Faculty of Sciences in Gabes, Gabes (Tunisia); Bouzid, Houcine [Promising Centre for Sensors and Electronic Devices (PCSED), Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia); Laboratoire des Matériaux Ferroélectriques, Faculté des Sciences de Sfax, Route Soukra Km 3 5, B.P. 802, F-3018 Sfax (Tunisia); Yousif, A. [Department of Physics, College of Science, Sultan Qaboos University, P.O. Box 36, Code 123, Al Khoud (Oman); Al-Hajry, Ali [Promising Centre for Sensors and Electronic Devices (PCSED), Najran University, P.O. Box 1988, Najran 11001 (Saudi Arabia)

    2014-09-01

    Highlights: • Iron oxides nanoparticles with different sizes are successfully synthesized using sol–gel method. • The obtained nanoparticles are mainly composed of maghemite phase (γ-Fe{sub 2}O{sub 3}). • A non-negligible coercive field suggests that the particles are ferromagnetic. • A mean heating efficiency of 30 W/g is obtained for the smallest particles at 110 kHz and 190 Oe. - Abstract: Iron oxides nanoparticles with different sizes are successfully synthesized using sol–gel method. X-ray diffraction (XRD) and Mössbauer spectroscopy show that the obtained nanoparticles are mainly composed of maghemite phase (γ-Fe{sub 2}O{sub 3}). XRD and transmission electron microscopy (TEM) results suggest that the nanoparticles have sizes ranging from 14 to 30 nm, which are indeed confirmed by large magnetic saturation and high blocking temperature. At room temperature, the observation of a non-negligible coercive field suggests that the particles are ferro/ferrimagnetic. The specific absorption rate (SAR) under an alternating magnetic field is investigated as a function of size, frequency and amplitude of the applied magnetic field. A mean heating efficiency of 30 W/g is obtained for the smallest particles at 110 kHz and 190 Oe, whereas further increase of particle size does not improve significantly the heating efficiency.

  12. Bottom up design of nanoparticles for anti-cancer diapeutics

    Needham, David; Arslanagic, Amina; Glud, Kasper

    2016-01-01

    for EPR uptake and tumor detection. We show that, while free-drug cannot be optimally administered in vivo, a nanoparticle formulation of orlistat could in principle represent a stable parenteral delivery system. The article ends with a brief discussion of what we see as the way forward in Individualized...... the feasibility of an idea: could we design, make, develop, and test the concept for treating metastatic cancer by, "Putting the Drug in the Cancer's Food? "Limit size" is the size of the cancer's food, ? the common Low Density Lipoprotein, (LDL) ~20 nm diameter. In this contribution to Pieter's LTAA we focus...... on the "bottom" (nucleation) and the "up" (growth) of "bottom-up design" as it applies to homogeneous nucleation of especially, hydrophobic drugs and the 8 physico-chemical stages and associated parameters that determine the initial size, and any subsequent coarsening, of a nanoparticle suspension. We show that...

  13. Targeted Nanoparticles for Kidney Cancer Therapy

    2014-12-01

    with logarithmic time scale. The instrument uses a 1.3 mm diameter by 60 mm long stainless steel probe that is immersed in the nanofluids to obtain the...the PL emission spectrum of Fe3O4 ferrofluid. An emission peak is observed at 416 nm upon excitation at 365 nm wavelength(3.39 eV) and Figure 2c...represents the corresponding PLE (excitation) spectrum for Fe3O4 nanoparticles at 416 nm (2.98 eV) emission of Fe3O4 nanoparticles. The observed result is

  14. Ultra-high sensitivity imaging of cancer using SERRS nanoparticles

    Kircher, Moritz F.

    2016-05-01

    "Surface-enhanced Raman spectroscopy" (SERS) nanoparticles have gained much attention in recent years for in silico, in vitro and in vivo sensing applications. Our group has developed novel generations of biocompatible "surfaceenhanced resonance Raman spectroscopy" (SERRS) nanoparticles as novel molecular imaging agents. Via rigorous optimization of the different variables contributing to the Raman enhancement, we were able to design SERRS nanoparticles with so far unprecedented sensitivity of detection under in vivo imaging conditions (femto-attomolar range). This has resulted in our ability to visualize, with a single nanoparticle, many different cancer types (after intravenous injection) in mouse models. The cancer types we have tested so far include brain, breast, esophagus, stomach, pancreas, colon, sarcoma, and prostate cancer. All mouse models used are state-of-the-art and closely mimic the tumor biology in their human counterparts. In these animals, we were able to visualize not only the bulk tumors, but importantly also microscopic extensions and locoregional satellite metastases, thus delineating for the first time the true extent of tumor spread. Moreover, the particles enable the detection of premalignant lesions. Given their inert composition they are expected to have a high chance for clinical translation, where we envision them to have an impact in various scenarios ranging from early detection, image-guidance in open or minimally invasive surgical procedures, to noninvasive imaging in conjunction with spatially offset (SESORS) Raman detection devices.

  15. Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment

    Zhang Z

    2017-02-01

    Full Text Available Zhen Zhang,1 Hanqing Qian,2 Mi Yang,2 Rutian Li,2 Jing Hu,1 Li Li,1 Lixia Yu,2 Baorui Liu,1,2 Xiaoping Qian1,2 1Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, 2Comprehensive Cancer Center, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute, Nanjing University, Nanjing, China Abstract: Gambogic acid (GA is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe­rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid (PLGA with red blood-cell membrane (RBCm, and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier. Keywords: gambogic acid, nanocarriers, RBCm-GA/PLGA nanoparticles, colorectal cancer

  16. Use of magnetic nanoparticles in the fight against cancer

    Herrera Castillo, Deyvit

    2009-01-01

    Nanotechnology and biotechnology have come together to form the nanobiotechnology; so, they are used as tools to prevent and treat diseases in the human body, even when they are little advanced. Also they have been used in regenerative medicine for the repair or replacement of damaged tissues or organs mainly the electronic nanodevices. The nanotherapy is used as an anticancer therapy in the diagnosis and treatment of disease and nano-systems are used as nanoparticles and nanodevices. The magnetic nanoparticles are exploited for the diagnosis and treatment of cancer where malignant and benign tumors are detected. (author) [es

  17. Establishment of a biophysical model to optimize endoscopic targeting of magnetic nanoparticles for cancer treatment

    Roeth AA

    2017-08-01

    Full Text Available Anjali A Roeth,1,* Ioana Slabu,2,* Martin Baumann,2 Patrick H Alizai,1 Maximilian Schmeding,1 Gernot Guentherodt,3 Thomas Schmitz-Rode,2 Ulf P Neumann1 1Department of General, Visceral and Transplant Surgery, University Hospital RWTH Aachen, 2Institute of Applied Medical Engineering, Helmholtz-Institute Aachen, RWTH Aachen, Aachen, 3Institute of Physics A, RWTH Aachen University, Aachen, Germany *These authors contributed equally to this work Abstract: Superparamagnetic iron oxide nanoparticles (SPION may be used for local tumor treatment by coupling them to a drug and accumulating them locally with magnetic field traps, that is, a combination of permanent magnets and coils. Thereafter, an alternating magnetic field generates heat which may be used to release the thermosensitively bound drug and for hyperthermia. Until today, only superficial tumors can be treated with this method. Our aim was to transfer this method into an endoscopic setting to also reach the majority of tumors located inside the body. To find the ideal endoscopic magnetic field trap, which accumulates the most SPION, we first developed a biophysical model considering anatomical as well as physical conditions. Entities of choice were esophageal and prostate cancer. The magnetic susceptibilities of different porcine and rat tissues were measured with a superconducting quantum interference device. All tissues showed diamagnetic behavior. The evaluation of clinical data (computed tomography scan, endosonography, surgical reports, pathological evaluation of patients gave insight into the topographical relationship between the tumor and its surroundings. Both were used to establish the biophysical model of the tumors and their surroundings, closely mirroring the clinical situation, in which we could virtually design, place and evaluate different electromagnetic coil configurations to find optimized magnetic field traps for each tumor entity. By simulation, we could show that the

  18. An induction heating device using planar coil with high amplitude alternating magnetic fields for magnetic hyperthermia.

    Wu, Zuhe; Zhuo, Zihang; Cai, Dongyang; Wu, Jian'an; Wang, Jie; Tang, Jintian

    2015-01-01

    Induction heating devices using the induction coil and magnetic nanoparticles (MNPs) are the way that the magnetic hyperthermia is heading. To facilitate the induction heating of in vivo magnetic nanoparticles in hyperthermia experiments on large animals. An induction heating device using a planar coil was designed with a magnetic field frequency of 328 kHz. The coil's magnetic field distribution and the device's induction heating performance on different concentrations of magnetic nanoparticles were measured. The alternating magnetic field produced in the axis position 165 mm away from the coil center is 40 Gs in amplitude; magnetic nanoparticles with a concentration higher than 80 mg. mL-1 can be heated up rapidly. Our results demonstrate that the device can be applied not only to in vitro and in small animal experiments of magnetic hyperthermia using MNPs, but also in large animal experiments.

  19. FDTD analysis of a noninvasive hyperthermia system for brain tumors.

    Yacoob, Sulafa M; Hassan, Noha S

    2012-08-14

    Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40-45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

  20. FDTD analysis of a noninvasive hyperthermia system for brain tumors

    Yacoob Sulafa M

    2012-08-01

    Full Text Available Abstract Background Hyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues. Methods The proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz. Results The obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue. Conclusions The proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

  1. Boosted Hyperthermia Therapy by Combined AC Magnetic and Photothermal Exposures in Ag/Fe3O4 Nanoflowers.

    Das, R; Rinaldi-Montes, N; Alonso, J; Amghouz, Z; Garaio, E; García, J A; Gorria, P; Blanco, J A; Phan, M H; Srikanth, H

    2016-09-28

    Over the past two decades, magnetic hyperthermia and photothermal therapy are becoming very promising supplementary techniques to well-established cancer treatments such as radiotherapy and chemotherapy. These techniques have dramatically improved their ability to perform controlled treatments, relying on the procedure of delivering nanoscale objects into targeted tumor tissues, which can release therapeutic killing doses of heat either upon AC magnetic field exposure or laser irradiation. Although an intense research effort has been made in recent years to study, separately, magnetic hyperthermia using iron oxide nanoparticles and photothermal therapy based on gold or silver plasmonic nanostructures, the full potential of combining both techniques has not yet been systematically explored. Here we present a proof-of-principle experiment showing that designing multifunctional silver/magnetite (Ag/Fe3O4) nanoflowers acting as dual hyperthermia agents is an efficient route for enhancing their heating ability or specific absorption rate (SAR). Interestingly, the SAR of the nanoflowers is increased by at least 1 order of magnitude under the application of both an external magnetic field of 200 Oe and simultaneous laser irradiation. Furthermore, our results show that the synergistic exploitation of the magnetic and photothermal properties of the nanoflowers reduces the magnetic field and laser intensities that would be required in the case that both external stimuli were applied separately. This constitutes a key step toward optimizing the hyperthermia therapy through a combined multifunctional magnetic and photothermal treatment and improving our understanding of the therapeutic process to specific applications that will entail coordinated efforts in physics, engineering, biology, and medicine.

  2. Parametric investigation of heating due to magnetic fluid hyperthermia in a tumor with blood perfusion

    Liangruksa, Monrudee [Department of Engineering Science and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061 (United States); Ganguly, Ranjan [Department of Power Engineering, Jadavpur University, Kolkata 700098 (India); Puri, Ishwar K., E-mail: ikpuri@vt.ed [Department of Engineering Science and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061 (United States)

    2011-03-15

    Magnetic fluid hyperthermia (MFH) is a cancer treatment that can selectively elevate the tumor temperature without significantly damaging the surrounding healthy tissue. Optimal MFH design requires a fundamental parametric investigation of the heating of soft materials by magnetic fluids. We model the problem of a spherical tumor and its surrounding healthy tissue that are heated by exciting a homogeneous dispersion of magnetic nanoparticles infused only into the tumor with an external AC magnetic field. The key dimensionless parameters influencing thermotherapy are the Peclet, Fourier, and Joule numbers. Analytical solutions for transient and steady hyperthermia provide correlations between these parameters and the portions of tumor and healthy tissue that are subjected to a threshold temperature beyond which they are damaged. Increasing the ratio of the Fourier and Joule numbers also increases the tumor temperature, but doing so can damage the healthy tissue. Higher magnetic heating is required for larger Peclet numbers due to the larger convection heat loss that occurs through blood perfusion. A comparison of the model predictions with previous experimental data for MFH applied to rabbit tumors shows good agreement. The optimal MFH conditions are identified based on two indices, the fraction I{sub T} of the tumor volume in which the local temperature is above a threshold temperature and the ratio I{sub N} of the damaged normal tissue volume to the tumor tissue volume that also lies above it. The spatial variation in the nanoparticle concentration is also considered. A Gaussian distribution provides efficacy while minimizing the possibility of generating a tumor hot spot. Varying the thermal properties of tumor and normal tissue alters I{sub T}and I{sub N} but the nature of the temperature distribution remains unchanged. - Research highlights: > Analytical model of magnetic fluid hyperthermia of tumor tissue perfused with magnetic nanoparticles that is surrounded

  3. Parametric investigation of heating due to magnetic fluid hyperthermia in a tumor with blood perfusion

    Liangruksa, Monrudee; Ganguly, Ranjan; Puri, Ishwar K.

    2011-01-01

    Magnetic fluid hyperthermia (MFH) is a cancer treatment that can selectively elevate the tumor temperature without significantly damaging the surrounding healthy tissue. Optimal MFH design requires a fundamental parametric investigation of the heating of soft materials by magnetic fluids. We model the problem of a spherical tumor and its surrounding healthy tissue that are heated by exciting a homogeneous dispersion of magnetic nanoparticles infused only into the tumor with an external AC magnetic field. The key dimensionless parameters influencing thermotherapy are the Peclet, Fourier, and Joule numbers. Analytical solutions for transient and steady hyperthermia provide correlations between these parameters and the portions of tumor and healthy tissue that are subjected to a threshold temperature beyond which they are damaged. Increasing the ratio of the Fourier and Joule numbers also increases the tumor temperature, but doing so can damage the healthy tissue. Higher magnetic heating is required for larger Peclet numbers due to the larger convection heat loss that occurs through blood perfusion. A comparison of the model predictions with previous experimental data for MFH applied to rabbit tumors shows good agreement. The optimal MFH conditions are identified based on two indices, the fraction I T of the tumor volume in which the local temperature is above a threshold temperature and the ratio I N of the damaged normal tissue volume to the tumor tissue volume that also lies above it. The spatial variation in the nanoparticle concentration is also considered. A Gaussian distribution provides efficacy while minimizing the possibility of generating a tumor hot spot. Varying the thermal properties of tumor and normal tissue alters I T and I N but the nature of the temperature distribution remains unchanged. - Research Highlights: →Analytical model of magnetic fluid hyperthermia of tumor tissue perfused with magnetic nanoparticles that is surrounded by healthy tissue

  4. Nanoparticles target early-stage breast cancer metastasis in vivo

    Goldman, Evgeniya; Zinger, Assaf; da Silva, Dana; Yaari, Zvi; Kajal, Ashima; Vardi-Oknin, Dikla; Goldfeder, Mor; Schroeder, Josh E.; Shainsky-Roitman, Janna; Hershkovitz, Dov; Schroeder, Avi

    2017-10-01

    Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. In this study we demonstrate that 100 nm liposomes target triple-negative murine breast-cancer metastases post intravenous administration. Metastatic breast cancer was induced in BALB/c mice either experimentally, by a tail vein injection of 4T1 cells, or spontaneously, after implanting a primary tumor xenograft. To track their biodistribution in vivo the liposomes were labeled with multi-modal diagnostic agents, including indocyanine green and rhodamine for whole-animal fluorescent imaging, gadolinium for magnetic resonance imaging (MRI), and europium for a quantitative biodistribution analysis. The accumulation of liposomes in the metastases peaked at 24 h post the intravenous administration, similar to the time they peaked in the primary tumor. The efficiency of liposomal targeting to the metastatic tissue exceeded that of a non-liposomal agent by 4.5-fold. Liposomes were detected at very early stages in the metastatic progression, including metastatic lesions smaller than 2 mm in diameter. Surprisingly, while nanoparticles target breast cancer metastasis, they may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue. This study highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.

  5. Albumin nanoparticles with synergistic antitumor efficacy against metastatic lung cancers.

    Kim, Bomi; Seo, Bohyung; Park, Sanghyun; Lee, Changkyu; Kim, Jong Oh; Oh, Kyung Taek; Lee, Eun Seong; Choi, Han-Gon; Youn, Yu Seok

    2017-10-01

    Albumin nanoparticles are well-known as effective drug carriers used to deliver hydrophobic chemotherapeutic agents. Albumin nanoparticles encapsulating curcumin and doxorubicin were fabricated using slightly modified nanoparticle albumin-bound (nab™) technology, and the synergistic effects of these two drugs were examined. Albumin nanoparticles encapsulating curcumin, doxorubicin, and both curcumin and doxorubicin were prepared using a high pressure homogenizer. The sizes of albumin nanoparticles were ∼130nm, which was considered to be suitable for the EPR (enhanced permeability and retention) effect. Albumin nanoparticles gradually released drugs over a period of 24h without burst effect. To confirm the synergistic effect of two drugs, in vitro cytotoxicity assay was performed using B16F10 melanoma cells. The cytotoxic effect on B16F10 melanoma cells was highest when co-treated with both curcumin and doxorubicin compared to single treatment of either curcumin and doxorubicin. The combined index calculated by medium-effect equation was 0.6069, indicating a synergistic effect. Results of confocal laser scanning microscopy and fluorescence-activated cell sorting corresponded to results from an in vitro cytotoxicity assay, indicating synergistic cytotoxicity induced by both drugs. A C57BL/6 mouse model induced by B16F10 lung metastasis was used to study in vivo therapeutic effects. When curcumin and doxorubicin were simultaneously treated, the metastatic melanoma mass in the lungs macroscopically decreased compared to curcumin or doxorubicin alone. Albumin nanoparticles encapsulating two anticancer drugs were shown to have an effective therapeutic result and would be an excellent way to treat resistant lung cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Hybrid Organic-Inorganic Bridged Silsesquioxane Nanoparticles for Cancer Nanomedicine

    Fatieiev, Yevhen

    2017-10-01

    It is well established that cancer is one of the leading causes of death globally. Its complete eradication requires early detection and intensive drug treatment. In many cases it might also require surgery. Unfortunately, current medicine is still more focused on cancer treatment rather than elimination of its reason. The mechanism of tumor emergence and development is quite complicated, although, we are constantly advancing in this field. Nanomedicine is envisioned as the silver bullet against cancer. Thus, nanoscale systems with therapeutic and diagnostic modalities can simultaneously perform several functions: accurate detection of tumor site, precise targeting, and controlled drug release inside abnormal cells and tissues while being nontoxic to healthy ones. Moreover, surface modification of such nanoparticles allows them to be invisible to the immune system and have longer blood circulating time. The performed research in this dissertation is completely based on hybrid organicinorganic bridged silsesquioxane (also known as organosilica) nanomaterials, therefore comprising "soft" organic/bioorganic part which can imitate certain biorelevant structures and facilitates successful escape from the immune system for more efficient accumulation in cancer cells, while "hard" inorganic part serves as a rigid and stable basis for the creation of cargo nanocarriers and imaging agents. This dissertation discusses the 5 critical points of safe biodegradable nanoplatforms, delivery of large biomolecules, and cytotoxicity regarding the shape of nanoparticles. As a result novel fluorescent biodegradable oxamide-based organosilica nanoparticles were developed, light-triggered surface charge reversal for large biomolecule delivery was applied with hollow bridged silsesquioxane nanomaterials, and biocompatibility of periodic mesoporous organosilicas with different morphologies was studied. Furthermore, the current achievements and future perspectives of mesoporous silica

  7. Hybrid Organic-Inorganic Bridged Silsesquioxane Nanoparticles for Cancer Nanomedicine

    Fatieiev, Yevhen

    2017-01-01

    It is well established that cancer is one of the leading causes of death globally. Its complete eradication requires early detection and intensive drug treatment. In many cases it might also require surgery. Unfortunately, current medicine is still more focused on cancer treatment rather than elimination of its reason. The mechanism of tumor emergence and development is quite complicated, although, we are constantly advancing in this field. Nanomedicine is envisioned as the silver bullet against cancer. Thus, nanoscale systems with therapeutic and diagnostic modalities can simultaneously perform several functions: accurate detection of tumor site, precise targeting, and controlled drug release inside abnormal cells and tissues while being nontoxic to healthy ones. Moreover, surface modification of such nanoparticles allows them to be invisible to the immune system and have longer blood circulating time. The performed research in this dissertation is completely based on hybrid organicinorganic bridged silsesquioxane (also known as organosilica) nanomaterials, therefore comprising "soft" organic/bioorganic part which can imitate certain biorelevant structures and facilitates successful escape from the immune system for more efficient accumulation in cancer cells, while "hard" inorganic part serves as a rigid and stable basis for the creation of cargo nanocarriers and imaging agents. This dissertation discusses the 5 critical points of safe biodegradable nanoplatforms, delivery of large biomolecules, and cytotoxicity regarding the shape of nanoparticles. As a result novel fluorescent biodegradable oxamide-based organosilica nanoparticles were developed, light-triggered surface charge reversal for large biomolecule delivery was applied with hollow bridged silsesquioxane nanomaterials, and biocompatibility of periodic mesoporous organosilicas with different morphologies was studied. Furthermore, the current achievements and future perspectives of mesoporous silica

  8. Size matters: nanoparticles in cancer therapy

    Khullar, Bhavya; Iqbal, Sarah

    2016-01-01

    Scientists at the CSIR-National Chemical Laboratory, Pune, in collaboration with universities in Lucknow and Aligarh, synthesized terbium oxide (Tb_2O_3) nanoparticles by putting a naturally occurring fungus into action. Commercially available Tb_4O_7 is reduced to Tb_2O_3 by incubating it with a suspension of Fusarium oxysporum in controlled conditions of pH and temperature. The aqueous crystals of Tb_2O_3, isolated from the fungal suspension, were stable and did not form aggregates or clumps. Hence, they could be isolated as crystals with long-term stability

  9. Multifunctional Nanoparticles for Prostate Cancer Therapy

    Chandratre, Shantanu S.; Dash, Alekha K.

    2014-01-01

    The relapse of cancer after first line therapy with anticancer agents is a common occurrence. This recurrence is believed to be due to the presence of a subpopulation of cells called cancer stem cells in the tumor. Therefore, a combination therapy which is susceptible to both types of cells is desirable. Delivery of this combinatorial approach in a nanoparticulate system will provide even a better therapeutic outcome in tumor targeting. The objective of this study was to develop and character...

  10. Mn{sub 0.5}Zn{sub 0.5}Fe{sub 2}O{sub 4} nanoparticles with high intrinsic loss power for hyperthermia therapy

    Phong, P.T., E-mail: phamthanhphong@tdt.edu.vn [Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City (Viet Nam); Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City (Viet Nam); Nam, P.H., E-mail: namph.ims@gmail.com [Institute of Materials Science, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Cau Giay District, Ha Noi City (Viet Nam); Manh, D.H. [Institute of Materials Science, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet Road, Cau Giay District, Ha Noi City (Viet Nam); Lee, In-Ja, E-mail: lij@dongguk.ac.kr [Department of Advanced Materials Chemistry, Dongguk University-Gyeongju, Dongdae-ro 123, Gyeongju-Si, Gyeongbuk 38066 (Korea, Republic of)

    2017-07-01

    Highlights: • Mn{sub 0.5}Zn{sub 0.5}FeO{sub 4} nanoparticles were synthesized using a hydrothermal method. • The coercivity at different temperatures was studied using the mixed coercivity model. • A superspin glass from strong interactions. • High intrinsic loss power was found to be comparable to that of ferrite and some commercial ferrofluids. - Abstract: Nanosized mixed ferrite Mn{sub 0.5}Zn{sub 0.5}Fe{sub 2}O{sub 4} with crystalline size ∼15 nm has been prepared by hydrothermal route. XRD patterns confirm that the crystallites have single phase cubic spinel structure. The dynamic scaling analysis on the frequency dependence of spin glass-like transition temperature well explains the model of a transition at finite temperature. The analysis gives critical exponent and parameters as: zν = 10.48, T{sub 0} = 190 K, f{sub 0} = 5.38 × 10{sup 10} and this confirms the occurrence of spin glass-like transition in Mn{sub 0.5}Zn{sub 0.5}Fe{sub 2}O{sub 4} particles. The saturation magnetization and the coercivity change with temperature. The effective magnetic anisotropy constant of sample was calculated using the law of approach to saturation. The coercivity at different temperatures was deduced using the mixed coercivity model. The calculated coercivity results are in a good agreement with the experimental ones. The magnetic heating ability of Mn{sub 0.5}Zn{sub 0.5}Fe{sub 2}O{sub 4} magnetic fluid was studied with an induction heating system. The calculated intrinsic loss power (ILP) was 3.75 g nHm{sup 2}/kg. This study indicates that the resulting Mn{sub 0.5}Zn{sub 0.5}Fe{sub 2}O{sub 4} nanoparticles are promising materials in magnetic hyperthermia.

  11. Magnetic nanowires and hyperthermia: How geometry and material affect heat production efficiency

    Contreras, Maria F.; Zaher, A.; Perez, Jose E.; Ravasi, Timothy; Kosel, Jü rgen

    2015-01-01

    Magnetic hyperthermia, which refers to the production of heat by magnetic nanostructures under an alternating magnetic field (AMF), has been previously investigated with superparamagnetic nanobeads as a cancer therapy method. Magnetic nanowires (NWs

  12. Targeting myeloid cells using nanoparticles to improve cancer immunotherapy.

    Amoozgar, Zohreh; Goldberg, Michael S

    2015-08-30

    While nanoparticles have traditionally been used to deliver cytotoxic drugs directly to tumors to induce cancer cell death, emerging data suggest that nanoparticles are likely to generate a larger impact on oncology through the delivery of agents that can stimulate antitumor immunity. Tumor-targeted nanocarriers have generally been used to localize chemotherapeutics to tumors and thus decrease off-target toxicity while enhancing efficacy. Challengingly, tumor heterogeneity and evolution render tumor-intrinsic approaches likely to succumb to relapse. The immune system offers exquisite specificity, cytocidal potency, and long-term activity that leverage an adaptive memory response. For this reason, the ability to manipulate immune cell specificity and function would be desirable, and nanoparticles represent an exciting means by which to perform such manipulation. Dendritic cells and tumor-associated macrophages are cells of the myeloid lineage that function as natural phagocytes, so they naturally take up nanoparticles. Dendritic cells direct the specificity and potency of cellular immune responses that can be targeted for cancer vaccines. Herein, we discuss the specific criteria needed for efficient vaccine design, including but not limited to the route of administration, size, morphology, surface charge, targeting ligands, and nanoparticle composition. In contrast, tumor-associated macrophages are critical mediators of immunosuppression whose trans-migratory abilities can be exploited to localize therapeutics to the tumor core and which can be directly targeted for elimination or for repolarization to a tumor suppressive phenotype. It is likely that a combination of targeting dendritic cells to stimulate antitumor immunity and tumor-associated macrophages to reduce immune suppression will impart significant benefits and result in durable antitumor responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Improving efficacy of hyperthermia in oncology by exploiting biological mechanisms

    van den Tempel, Nathalie; Horsman, Michael R; Kanaar, Roland

    2016-01-01

    It has long been established that hyperthermia increases the therapeutic benefit of radiation and chemotherapy in cancer treatment. During the last few years there have been substantial technical improvements in the sources used to apply and measure heat, which greatly increases enthusiasm for th...

  14. Hyperthermia and hyperglycemia in oncology

    Zhavrid, Eh.A.; Osinskij, S.P.; Fradkin, S.Z.

    1987-01-01

    Consideration is being given to publication data and results of author's investigations into the effect of hyperthermia and hyperglycemia on physico-chemical characteristics and growth of various experimental tumors. Factors, modifying thermosensitivity, mechanisms of hyperthermia effect, various aspects of thermochimio- and thermoradiotherapy have been analyzed. Effect of artificial hyperglycemia on metabolism and kinetics of tumor and some normal cells is considered in detail. Many data, testifying to sufficient growth of efficiency of oncologic patient treatment under conditions of multimodality therapy including hyperthermia and hyperglycemia are presented

  15. One-step microwave-assisted synthesis of water-dispersible Fe3O4 magnetic nanoclusters for hyperthermia applications

    Sathya, Ayyappan; Kalyani, S.; Ranoo, Surojit; Philip, John

    2017-10-01

    To realize magnetic hyperthermia as an alternate stand-alone therapeutic procedure for cancer treatment, magnetic nanoparticles with optimal performance, within the biologically safe limits, are to be produced using simple, reproducible and scalable techniques. Herein, we present a simple, one-step approach for synthesis of water-dispersible magnetic nanoclusters (MNCs) of superparamagnetic iron oxide by reducing of Fe2(SO4)3 in sodium acetate (alkali), poly ethylene glycol (capping ligand), and ethylene glycol (solvent and reductant) in a microwave reactor. The average size and saturation magnetization of the MNC's are tuned from 27 to 52 nm and 32 to 58 emu/g by increasing the reaction time from 10 to 600 s. Transmission electron microscopy images reveal that each MNC composed of large number of primary Fe3O4 nanoparticles. The synthesised MNCs show excellent colloidal stability in aqueous phase due to the adsorbed PEG layer. The highest SAR value of 215 ± 10 W/gFe observed in 52 nm size MNC at a frequency of 126 kHz and field of 63 kA/m suggest the potential use of these MNC in hyperthermia applications. This study further opens up the possibilities to develop metal ion-doped MNCs with tunable sizes suitable for various biomedical applications using microwave assisted synthesis.

  16. Gold nanoparticles enlighten the future of cancer theranostics

    Guo J

    2017-08-01

    Full Text Available Jianfeng Guo,1 Kamil Rahme,2–4 Yan He,1 Lin-Lin Li,5 Justin D Holmes,3,4 Caitriona M O’Driscoll6 1School of Pharmaceutical Sciences, Jilin University, Changchun, China; 2Department of Sciences, Faculty of Natural and Applied Science, Notre Dame University (Louaize, Zouk Mosbeh, Lebanon; 3Department of Chemistry, Tyndall National Institute, University College Cork, Cork, 4AMBER@CRANN, Trinity College Dublin, Dublin, Ireland; 5The First Hospital of Jilin University, Changchun, China; 6Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland Abstract: Development of multifunctional nanomaterials, one of the most interesting and advanced research areas in the field of nanotechnology, is anticipated to revolutionize cancer diagnosis and treatment. Gold nanoparticles (AuNPs are now being widely utilized in bioimaging and phototherapy due to their tunable and highly sensitive optical and electronic properties (the surface plasmon resonance. As a new concept, termed “theranostics,” multifunctional AuNPs may contain diagnostic and therapeutic functions that can be integrated into one system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. In this review, the important properties of AuNPs relevant to diagnostic and phototherapeutic applications such as structure, shape, optics, and surface chemistry are described. Barriers for translational development of theranostic AuNPs and recent advances in the application of AuNPs for cancer diagnosis, photothermal, and photodynamic therapy are discussed. Keywords: multifunctional gold nanoparticles, cancer bioimaging, cancer photothermal and photodynamic therapy

  17. Smart human serum albumin-indocyanine green nanoparticles generated by programmed assembly for dual-modal imaging-guided cancer synergistic phototherapy.

    Sheng, Zonghai; Hu, Dehong; Zheng, Mingbin; Zhao, Pengfei; Liu, Huilong; Gao, Duyang; Gong, Ping; Gao, Guanhui; Zhang, Pengfei; Ma, Yifan; Cai, Lintao

    2014-12-23

    Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a light-activated local treatment modality that is under intensive preclinical and clinical investigations for cancer. To enhance the treatment efficiency of phototherapy and reduce the light-associated side effects, it is highly desirable to improve drug accumulation and precision guided phototherapy for efficient conversion of the absorbed light energy to reactive oxygen species (ROS) and local hyperthermia. In the present study, a programmed assembly strategy was developed for the preparation of human serum albumin (HSA)-indocyanine green (ICG) nanoparticles (HSA-ICG NPs) by intermolecular disulfide conjugations. This study indicated that HSA-ICG NPs had a high accumulation with tumor-to-normal tissue ratio of 36.12±5.12 at 24 h and a long-term retention with more than 7 days in 4T1 tumor-bearing mice, where the tumor and its margin, normal tissue were clearly identified via ICG-based in vivo near-infrared (NIR) fluorescence and photoacoustic dual-modal imaging and spectrum-resolved technology. Meanwhile, HSA-ICG NPs efficiently induced ROS and local hyperthermia simultaneously for synergetic PDT/PTT treatments under a single NIR laser irradiation. After an intravenous injection of HSA-ICG NPs followed by imaging-guided precision phototherapy (808 nm, 0.8 W/cm2 for 5 min), the tumor was completely suppressed, no tumor recurrence and treatments-induced toxicity were observed. The results suggest that HSA-ICG NPs generated by programmed assembly as smart theranostic nanoplatforms are highly potential for imaging-guided cancer phototherapy with PDT/PTT synergistic effects.

  18. Combined effects of hyperthermia and radiation in cultured mammalian cells

    Ben-Hur, E.; Elkind, M.M.; Riklis, E.

    1977-01-01

    Hyperthermia (temperatures of 39 0 C or higher) enhances the killing of mammalian cells by ionizing radiation (fission-spectrum neutrons and x-rays). The nature and the magnitude of the enhanced radiation killing varies with temperature and for a fixed temperature during irradiation, the enhanced lethality varies inversely with dose rate. For temperatures up to 41 0 C, dose fractionation measurements indicate that hyperthermia inhibits the repair of sublethal damage. At higher temperatures, the expression of potentially lethal damage is enhanced. Since the effect of heat is greatest in cells irradiated during DNA synthesis, the radiation age-response pattern is flattened by hyperthermia. In addition to the enhanced cell killing described above, three other features of the effect of hyperthermia are important in connection with the radiation treatment of cancer. The first is that heat selectively sensitizes S-phase cells to radiation. The second is that it takes radiation survivors 10 to 20 hrs after a modest heat treatment to recover their ability to repair sublethal damage. And the third is that hyperthermia reduces the magnitude of the oxygen enhancement ratio. Thus, heat if applied selectively, could significantly increase the margin of damage between tumors and normal tissues

  19. Outcomes after environmental hyperthermia.

    LoVecchio, Frank; Pizon, Anthony F; Berrett, Christopher; Balls, Adam

    2007-05-01

    This study was conducted to describe the characteristics and outcomes of patients who presented to the emergency department (ED) with presumed environmental hyperthermia. A retrospective chart review was performed in 2 institutions with patients who were seen in the ED and had a discharge diagnosis of hyperthermia, heat stroke, heat exhaustion, or heat cramps. Exclusion criteria were an alternative diagnosis potentially explaining the hyperthermia (pneumonia, etc). Research assistants, who were blinded to the purpose of the study, performed a systematic chart review after a structured training session. If necessary, a third reviewer acted as a tiebreaker. Data regarding patient demographics, comorbidities, vital signs, laboratory results, and short-term outcome were collected. Data were analyzed with Excel and STATA software. We enrolled 52 patients with a mean age of 42.6 years (range, 0.4-81 years) from August 1, 2003 to August 31, 2005. The mean high daily temperature was 103.6 degrees F (range, 88-118 degrees F). At presentation, the mean body temperature was 105.1 degrees F (range, 100.2-111.2 degrees F) and the Glasgow Coma Scale score was less than 14 in 36 (69.2%) patients. Laboratory results demonstrated that 21 (40.4%) patients had a creatinine level of more than 1.5 mg/dL, 35 (67.3%) patients had a creatine kinase (CK) of more than 200 U/L, 30 patients (57.7%) had a prothrombin time of more than 13 seconds, 29 (55.8%) patients had an aspartate aminotransferase (AST) of more than 45 U/L, and only 3 patients (5.7%) had a glucose of less than 60 mg/dL. Ethanol or illicit drugs were involved in 18 (34.6%) cases. The mean hospital stay was 4.7 days (range, 1-30 days), and there were 15 deaths (28.8%). A kappa score for interreviewer reliability was 0.69. Major limitations were the retrospective nature and lack of homogeneity in patient evaluation and test ordering. Hyperthermic patients with higher initial temperatures, hypotension, or low Glasgow Coma Scale

  20. Photothermal therapy of cancer cells using magnetic carbon nanoparticles

    Vardarajan, V.; Gu, L.; Kanneganti, A.; Mohanty, S. K.; Koymen, A. R.

    2011-03-01

    Photothermal therapy offers a solution for the destruction of cancer cells without significant collateral damage to otherwise healthy cells. Several attempts are underway in using carbon nanoparticles (CNPs) and nanotubes due to their excellent absorption properties in the near-infrared spectrum of biological window. However, minimizing the required number of injected nanoparticles, to ensure minimal cytotoxicity, is a major challenge. We report on the introduction of magnetic carbon nanoparticles (MCNPs) onto cancer cells, localizing them in a desired region by applying an external magnetic field and irradiating them with a near-infrared laser beam. The MCNPs were prepared in Benzene, using an electric plasma discharge, generated in the cavitation field of an ultrasonic horn. The CNPs were made ferromagnetic by use of Fe-electrodes to dope the CNPs, as confirmed by magnetometry. Transmission electron microscopy measurements showed the size distribution of these MCNPs to be in the range of 5-10 nm. For photothermal irradiation, a tunable continuous wave Ti: Sapphire laser beam was weakly focused on to the cell monolayer under an inverted fluorescence microscope. The response of different cell types to photothermal irradiation was investigated. Cell death in the presence of both MCNPs and laser beam was confirmed by morphological changes and propidium iodide fluorescence inclusion assay. The results of our study suggest that MCNP based photothermal therapy is a promising approach to remotely guide photothermal therapy.

  1. Genetics Home Reference: malignant hyperthermia

    ... 1722-30. Review. Citation on PubMed Litman RS, Rosenberg H. Malignant hyperthermia: update on susceptibility testing. JAMA. ... 27(10):977-89. Review. Citation on PubMed Rosenberg H, Davis M, James D, Pollock N, Stowell ...

  2. Novel Synergistic Therapy for Metastatic Breast Cancer: Magnetic Nanoparticle Hyperthermia of the Neovasculature Enhanced by a Vascular Disruption Agent

    2013-04-01

    bovine serum and antibiotics (VEC Technologies) on gelatin coated surface. SK- 0V-3 ovarian adenocarcinoma cell line was cultured at 37° C under a...are formed from mouse cells. Unlike xenograft models, which require an immunocompromised mouse to avoid rejection of the tumor, the PyMT mouse

  3. Hyperthermia and fatigue

    Nybo, Lars

    2008-01-01

    The present review addresses mechanisms of importance for hyperthermia-induced fatigue during short intense activities and prolonged exercise in the heat. Inferior performance during physical activities with intensities that elicit maximal oxygen uptake is to a large extent related to perturbation...... of the cardiovascular function, which eventually reduces arterial oxygen delivery to the exercising muscles. Accordingly, aerobic energy turnover is impaired and anaerobic metabolism provokes peripheral fatigue. In contrast, metabolic disturbances of muscle homeostasis are less important during prolonged exercise...... in the heat, because increased oxygen extraction compensates for the reduction in systemic blood flow. The decrease in endurance seems to involve changes in the function of the central nervous system (CNS) that lead to fatigue. The CNS fatigue appears to be influenced by neurotransmitter activity...

  4. Direct observation of nanoparticle-cancer cell nucleus interactions.

    Dam, Duncan Hieu M; Lee, Jung Heon; Sisco, Patrick N; Co, Dick T; Zhang, Ming; Wasielewski, Michael R; Odom, Teri W

    2012-04-24

    We report the direct visualization of interactions between drug-loaded nanoparticles and the cancer cell nucleus. Nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were actively transported to the nucleus and induced major changes to the nuclear phenotype via nuclear envelope invaginations near the site of the construct. The number of local deformations could be increased by ultrafast, light-triggered release of the aptamers from the surface of the gold nanostars. Cancer cells with more nuclear envelope folding showed increased caspase 3 and 7 activity (apoptosis) as well as decreased cell viability. This newly revealed correlation between drug-induced changes in nuclear phenotype and increased therapeutic efficacy could provide new insight for nuclear-targeted cancer therapy.

  5. Gold nanoparticles for cancer theranostics — A brief update

    Ning Zhao

    2016-07-01

    Full Text Available Gold nanoparticles (AuNPs exhibit superior optical and physical properties for more effective treatment of cancer through incorporating both diagnostic and therapeutic functions into one single platform. The ability to passively accumulate on tumor cells provides AuNPs the opportunity to become an attractive contrast agent for X-ray based computed tomography (CT imaging in vivo. Because of facile surface modification, various size and shape of AuNPs have been extensively functionalized and applied as active nanoprobes and drug carriers for cancer targeted theranostics. Moreover, their capabilities on producing photoacoustic (PA signals and photothermal effects have been used to image and treat tumor progression, respectively. Herein, we review the developments of AuNPs as cancer diagnostics and chemotherapeutic drug vector, summarizing strategies for tumor targeting and their applications in vitro and in vivo.

  6. The application of nanoparticles in diagnosis and theranostics of gastric cancer.

    Li, Rutian; Liu, Baorui; Gao, Jiahui

    2017-02-01

    Gastric cancer is the fourth most common cancer and the second leading cause of cancer related death worldwide. For the diagnosis of gastric cancer, apart from regular systemic imaging, the locoregional imaging is also of great importance. Moreover, there are still other ways for the detecting of gastric cancer, including the early detection of gastric cancer by endoscopy, the detection of gastric-cancer related biomarkers and the detection of circulating tumor cells (CTCs) of gastric cancer. However, conventional diagnostic methods are usually lack of specificity and sensitivity. Nanoparticles provide many benefits in the diagnosis of gastric cancer. Besides, nanoparticles are capable of integrating the functions of diagnosis and treatment together (theranostics). In this paper, we reviewed the applications of nanoparticles in diagnosis and theranostics of gastric cancer in the above mentioned aspects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Numerical modeling for an electric-field hyperthermia applicator

    Wu, Te-Kao; Chou, C. K.; Chan, K. W.; Mcdougall, J.

    1993-01-01

    Hyperthermia, in conjunction with radiation and chemotherapy for treatment of cancers, is an area of current concern. Experiments have shown that hyperthermia can increase the potency of many chemotherapy drugs and the effectiveness of radiation for treating cancer. A combination of whole body or regional hyperthermia with chemotherapy or radiation should improve treatment results. Conventional methods for inducing whole body hyperthermia, such as exposing a patient in a radiant cabinet or under a hot water blanket, conduct heat very slowly from the skin to the body core. Thus a more efficient system, such as the three-plate electric-field hyperthermia applicator (EHA), is developed. This three-plate EHA has one top plate over and two lower plates beneath the patient. It is driven at 27.12 MHz with 500 Watts through a matching circuit. Using this applicator, a 50 kg pig was successfully heated to 42 C within 45 minutes. However, phantom and animal studies have indicated non-uniform heating near the side of the body. In addition, changes in the size and distance between the electrode plates can affect the heating (or electromagnetic field) pattern. Therefore, numerical models using the method of moments (MOM) or the finite difference time domain (FDTD) technique are developed to optimize the heating pattern of this EHA before it is used for human trials. The accuracy of the numerical modeling has been achieved by the good agreement between the MOM and FDTD results for the three-plate EHA without a biological body. The versatile FDTD technique is then applied to optimize the EHA design with a human body. Both the numerical and measured data in phantom blocks will be presented. The results of this study will be used to design an optimized system for whole body or regional hyperthermia.

  8. Plumbagin Nanoparticles Induce Dose and pH Dependent Toxicity on Prostate Cancer Cells.

    Nair, Harikrishnan A; Snima, K S; Kamath, Ravindranath C; Nair, Shantikumar V; Lakshmanan, Vinoth-Kumar

    2015-01-01

    Stable nano-formulation of Plumbagin nanoparticles from Plumbago zeylanica root extract was explored as a potential natural drug against prostate cancer. Size and morphology analysis by DLS, SEM and AFM revealed the average size of nanoparticles prepared was 100±50nm. In vitro cytotoxicity showed concentration and time dependent toxicity on prostate cancer cells. However, plumbagin crude extract found to be highly toxic to normal cells when compared to plumbagin nanoformulation, thus confirming nano plumbagin cytocompatibility with normal cells and dose dependent toxicity to prostate cells. In vitro hemolysis assay confirmed the blood biocompatibility of the plumbagin nanoparticles. In wound healing assay, plumbagin nanoparticles provided clues that it might play an important role in the anti-migration of prostate cancer cells. DNA fragmentation revealed that partial apoptosis induction by plumbagin nanoparticles could be expected as a potent anti-cancer effect towards prostate cancer.

  9. Gold Nanoparticle Microwave Synthesis

    Krantz, Kelsie E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Christian, Jonathan H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Coopersmith, Kaitlin [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Washington, II, Aaron L. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Murph, Simona H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-07-27

    At the nanometer scale, numerous compounds display different properties than those found in bulk material that can prove useful in areas such as medicinal chemistry. Gold nanoparticles, for example, display promise in newly developed hyperthermia therapies for cancer treatment. Currently, gold nanoparticle synthesis is performed via the hot injection technique which has large variability in final particle size and a longer reaction time. One underdeveloped area by which these particles could be produced is through microwave synthesis. To initiate heating, microwaves agitate polar molecules creating a vibration that gives off the heat energy needed. Previous studies have used microwaves for gold nanoparticle synthesis; however, polar solvents were used that partially absorbed incident microwaves, leading to partial thermal heating of the sample rather than taking full advantage of the microwave to solely heat the gold nanoparticle precursors in a non-polar solution. Through this project, microwaves were utilized as the sole heat source, and non-polar solvents were used to explore the effects of microwave heating only as pertains to the precursor material. Our findings show that the use of non-polar solvents allows for more rapid heating as compared to polar solvents, and a reduction in reaction time from 10 minutes to 1 minute; this maximizes the efficiency of the reaction, and allows for reproducibility in the size/shape of the fabricated nanoparticles.

  10. Gold Nanoparticle Microwave Synthesis

    Krantz, Kelsie E.; Christian, Jonathan H.; Coopersmith, Kaitlin; Washington II, Aaron L.; Murph, Simona H.

    2016-01-01

    At the nanometer scale, numerous compounds display different properties than those found in bulk material that can prove useful in areas such as medicinal chemistry. Gold nanoparticles, for example, display promise in newly developed hyperthermia therapies for cancer treatment. Currently, gold nanoparticle synthesis is performed via the hot injection technique which has large variability in final particle size and a longer reaction time. One underdeveloped area by which these particles could be produced is through microwave synthesis. To initiate heating, microwaves agitate polar molecules creating a vibration that gives off the heat energy needed. Previous studies have used microwaves for gold nanoparticle synthesis; however, polar solvents were used that partially absorbed incident microwaves, leading to partial thermal heating of the sample rather than taking full advantage of the microwave to solely heat the gold nanoparticle precursors in a non-polar solution. Through this project, microwaves were utilized as the sole heat source, and non-polar solvents were used to explore the effects of microwave heating only as pertains to the precursor material. Our findings show that the use of non-polar solvents allows for more rapid heating as compared to polar solvents, and a reduction in reaction time from 10 minutes to 1 minute; this maximizes the efficiency of the reaction, and allows for reproducibility in the size/shape of the fabricated nanoparticles.

  11. Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics

    Patra, Sujata; Mukherjee, Sudip; Barui, Ayan Kumar; Ganguly, Anirban; Sreedhar, Bojja; Patra, Chitta Ranjan

    2015-01-01

    In the present article, we demonstrate the delivery of anti-cancer drug to the cancer cells using biosynthesized gold and silver nanoparticles (b-AuNP & b-AgNP). The nanoparticles synthesized by using Butea monosperma (BM) leaf extract are thoroughly characterized by various analytical techniques. Both b-AuNP and b-AgNP are stable in biological buffers and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2 & A549). Administration of nanoparticle based drug delivery systems (DDSs) using doxorubicin (DOX) [b-Au-500-DOX and b-Ag-750-DOX] shows significant inhibition of cancer cell proliferation (B16F10, MCF-7) compared to pristine drug. Therefore, we strongly believe that biosynthesized nanoparticles will be useful for the development of cancer therapy using nanomedicine approach in near future. - Highlights: • Biosynthesis of gold and silver nanoparticles using plant leaf extract • The approach is clean, efficient, eco-friendly & economically safe. • Biosynthesized nanoparticles are biocompatible towards normal and cancer cells. • Design and development of biosynthesized nanoparticle based drug delivery systems • Biosynthesized nanoparticles could be useful for cancer and other diseases

  12. Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics

    Patra, Sujata; Mukherjee, Sudip; Barui, Ayan Kumar; Ganguly, Anirban [Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana State (India); Sreedhar, Bojja [Inorganic and Physical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana State (India); Patra, Chitta Ranjan, E-mail: crpatra@iict.res.in [Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana State (India)

    2015-08-01

    In the present article, we demonstrate the delivery of anti-cancer drug to the cancer cells using biosynthesized gold and silver nanoparticles (b-AuNP & b-AgNP). The nanoparticles synthesized by using Butea monosperma (BM) leaf extract are thoroughly characterized by various analytical techniques. Both b-AuNP and b-AgNP are stable in biological buffers and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2 & A549). Administration of nanoparticle based drug delivery systems (DDSs) using doxorubicin (DOX) [b-Au-500-DOX and b-Ag-750-DOX] shows significant inhibition of cancer cell proliferation (B16F10, MCF-7) compared to pristine drug. Therefore, we strongly believe that biosynthesized nanoparticles will be useful for the development of cancer therapy using nanomedicine approach in near future. - Highlights: • Biosynthesis of gold and silver nanoparticles using plant leaf extract • The approach is clean, efficient, eco-friendly & economically safe. • Biosynthesized nanoparticles are biocompatible towards normal and cancer cells. • Design and development of biosynthesized nanoparticle based drug delivery systems • Biosynthesized nanoparticles could be useful for cancer and other diseases.

  13. Evaluation of the sonosensitizing properties of nano-graphene oxide in comparison with iron oxide and gold nanoparticles

    Beik, Jaber; Abed, Ziaeddin; Shakeri-Zadeh, Ali; Nourbakhsh, Mitra; Shiran, Mohammad Bagher

    2016-07-01

    In cancer hyperthermia, ultrasound is considered as an appropriate source of energy to achieve desired therapeutic levels of heating. It is assumed that such a heating is targeted to cancer cells by using nanoparticles as sonosensitization agents. Here, we report the sonosensitizing effects of Nano-Graphene Oxide (NGO) and compare them with gold nanoparticles (AuNPs), Iron Oxide nanoparticles (IONPs). Experiments were conducted to explore the effects of nanoparticle type and concentration, as well as ultrasound power, on transient heating up of the solutions exposed by 1 MHz ultrasound. Nanoparticles concentration was selected from 0.25 to 2.5 mg/ml and the solutions were exposed by ultrasound powers from 1 to 8 W. Real time temperature monitoring was done by a thermocouple and obtained data was analyzed. Temperature profiles of various nanoparticle solutions showed the higher heating rates, in comparison to water. Heating rise was strongly depended on nanoparticles concentration and ultrasound power. AuNPs showed a superior efficiency in heat generation enhancement in comparison to IONPs and NGO. Our result supports the idea of sonosensitizing capabilities of AuNPs, IONPs, and NGO. Targeted hyperthermia may be achievable by preferential loading of tumor with nanoparticles and subsequent ultrasound irradiation.

  14. Cancer-selective, single agent chemoradiosensitising gold nanoparticles

    Grellet, Sophie; Tzelepi, Konstantina; Roskamp, Meike; Williams, Phil; Sharif, Aquila; Slade-Carter, Richard; Goldie, Peter; Whilde, Nicky; ?mia?ek, Ma?gorzata A.; Mason, Nigel J.; Golding, Jon P.

    2017-01-01

    Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards can...

  15. Long duration mild temperature hyperthermia and brachytherapy.

    Armour, E P; Raaphorst, G P

    2004-03-01

    Combining long duration mild temperature hyperthermia (LDMH) and low dose-rate (LDR) brachytherapy to enhance therapeutic killing of cancer cells was proposed many years ago. The cellular and tumour research that supports this hypothesis is presented in this review. Research describing LDMH interaction with pulsed brachytherapy and high dose-rate brachytherapy using clinically relevant parameters are compared with LDMH/LDR brachytherapy. The mechanism by which LDMH sensitizes LDR has been established as the inhibition of sublethal damage repair. The molecular mechanisms have been shown to involve DNA repair enzymes, but the exact nature of these processes is still under investigation. The relative differences between LDMH interactions with human and rodent cells are presented to help in the understanding of possible roles of LDMH in clinical application. The role of LDMH in modifying tumour blood flow and its possible role in LDR sensitization of tumours is also presented. The positive aspects of LDMH-brachytherapy for clinical application are sixfold; (1) the thermal goals (temperature, time and volume) are achievable with currently available technology, (2) the hyperthermia by itself has no detectable toxic effects, (3) thermotolerance appears to play a minor if any role in radiation sensitization, (4) TER of around 2 can be expected, (5) hypoxic fraction may be decreased due to blood flow modification and (6) simultaneous chemotherapy may also be sensitized. Combined LDMH and brachytherapy is a cancer therapy that has established biological rationale and sufficient technical and clinical advancements to be appropriately applied. This modality is ripe for clinical testing.

  16. Photothermal effects and toxicity of Fe{sub 3}O{sub 4} nanoparticles via near infrared laser irradiation for cancer therapy

    Dunn, Andrew W. [The Materials Science and Engineering Program, Dept. of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH 45221 (United States); Ehsan, Sadat M.; Mast, David [Department of Physics, University of Cincinnati, Cincinnati, OH 45221 (United States); Pauletti, Giovanni M. [The James L. Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267 (United States); Xu, Hong [Nano Biomedical Research Center, School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030 (China); Zhang, Jiaming; Ewing, Rodney C. [Department of Geological and Environmental Sciences, Stanford University, Stanford, CA 94305 (United States); Shi, Donglu, E-mail: donglu.shi@uc.edu [The Materials Science and Engineering Program, Dept. of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH 45221 (United States); Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai 200120 (China)

    2015-01-01

    The photothermal effect of magnetite (Fe{sub 3}O{sub 4}) nanoparticles was characterized by photonic absorption in the near-infrared (NIR) region. Upon laser irradiation at 785 nm, the Fe{sub 3}O{sub 4} nanoparticles generate localized hyperthermia in tumorous lesions, which is an effective strategy for cancer therapy; however, uncoated magnetite possesses an innate toxicity which can lead to drawbacks in the clinical setting. To reduce innate toxicity, a poly(acrylic acid) (PAA) coating on the nanoparticles was investigated in order to determine the alterations to stability and the degree of toxicity in an attempt to create a higher utility vector. It was found that the PAA coating significantly reduced the innate toxicity of the uncoated magnetite. Furthermore, the efficacy of PAA-coated magnetite nanoparticles (PAA-Fe{sub 3}O{sub 4}) was investigated for treating MDA-MB-231 (human mammary gland adenocarcinoma) cultures in viable concentration ranges (0.1–0.5 mg/ml). An appropriate PAA-Fe{sub 3}O{sub 4} concentration range was then established for inducing significant cell death by hyperthermic ablation, but not through innate toxicity. - Highlights: • Uncoated magnetite NPs possess high innate toxicity in MDA-MB-231 cultures. • PAA coating significantly reduces innate toxicity and stabilizes magnetite NPs. • Thermal ablation begins at 0.2 mg/ml for PAA-Fe{sub 3}O{sub 4} at 785 nm NIR laser, 38.5 kW/m{sup 2}. • 38.5 kW/m{sup 2} does not significantly affect MDA-MB-231 viability in-vitro.

  17. Sustained Cytotoxicity of Wogonin on Breast Cancer Cells by Encapsulation in Solid Lipid Nanoparticles

    Jong-Suep Baek

    2018-03-01

    Full Text Available While wogonin has been known to have cytotoxicity against various cancer cells, its bioavailability and cytotoxicity are low due to its low water solubility. Therefore, wogonin-loaded solid lipid nanoparticles were fabricated using a hot-melted evaporation technique. The highest solubility of wogonin was observed in stearic acid. Hence, wogonin-loaded solid lipid nanoparticles were composed of stearic acid as the lipid matrix. The physicochemical properties of the wogonin-loaded solid lipid nanoparticles were evaluated by dynamic laser scattering and scanning electron microscopy. The wogonin-loaded solid lipid nanoparticles exhibited sustained and controlled release up to 72 h. In addition, it was observed that the wogonin-loaded solid lipid nanoparticles exhibited enhanced cytotoxicity and inhibited poly (ADP-ribose polymerase in MCF-7 breast cancer cells. Overall, the results indicate that wogonin-loaded solid lipid nanoparticles could be an efficient delivery system for the treatment of breast cancer.

  18. Synthesis and characterization of near IR fluorescent albumin nanoparticles for optical detection of colon cancer

    Cohen, Sarit; Pellach, Michal [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel); Kam, Yossi [Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120 (Israel); Grinberg, Igor; Corem-Salkmon, Enav [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel); Rubinstein, Abraham [Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120 (Israel); Margel, Shlomo, E-mail: shlomo.margel@mail.biu.ac.il [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel)

    2013-03-01

    Near IR (NIR) fluorescent human serum albumin (HSA) nanoparticles hold great promise as contrast agents for tumor diagnosis. HSA nanoparticles are considered to be biocompatible, non-toxic and non-immunogenic. In addition, NIR fluorescence properties of these nanoparticles are important for in vivo tumor diagnostics, with low autofluorescence and relatively deep penetration of NIR irradiation due to low absorption of biomatrices. The present study describes the synthesis of new NIR fluorescent HSA nanoparticles, by entrapment of a NIR fluorescent dye within the HSA nanoparticles, which also significantly increases the photostability of the dye. Tumor-targeting ligands such as peanut agglutinin (PNA) and anti-carcinoembryonic antigen antibodies (anti-CEA) were covalently conjugated to the NIR fluorescent albumin nanoparticles, increasing the potential fluorescent signal in tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent HSA nanoparticles was demonstrated in a chicken embryo model and a rat model. In future work we also plan to encapsulate cancer drugs such as doxorubicin within the NIR fluorescent HSA nanoparticles for both colon cancer imaging and therapy. - Highlights: Black-Right-Pointing-Pointer Near IR human serum albumin nanoparticles were synthesized and characterized. Black-Right-Pointing-Pointer Nanoparticles were shown to be physically and chemically stable and photostable. Black-Right-Pointing-Pointer Tumor-targeting ligands were covalently conjugated to the nanoparticles. Black-Right-Pointing-Pointer Specific colon cancer tumor detection was demonstrated in chicken-embryo and rat models.

  19. Synthesis and characterization of near IR fluorescent albumin nanoparticles for optical detection of colon cancer

    Cohen, Sarit; Pellach, Michal; Kam, Yossi; Grinberg, Igor; Corem-Salkmon, Enav; Rubinstein, Abraham; Margel, Shlomo

    2013-01-01

    Near IR (NIR) fluorescent human serum albumin (HSA) nanoparticles hold great promise as contrast agents for tumor diagnosis. HSA nanoparticles are considered to be biocompatible, non-toxic and non-immunogenic. In addition, NIR fluorescence properties of these nanoparticles are important for in vivo tumor diagnostics, with low autofluorescence and relatively deep penetration of NIR irradiation due to low absorption of biomatrices. The present study describes the synthesis of new NIR fluorescent HSA nanoparticles, by entrapment of a NIR fluorescent dye within the HSA nanoparticles, which also significantly increases the photostability of the dye. Tumor-targeting ligands such as peanut agglutinin (PNA) and anti-carcinoembryonic antigen antibodies (anti-CEA) were covalently conjugated to the NIR fluorescent albumin nanoparticles, increasing the potential fluorescent signal in tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent HSA nanoparticles was demonstrated in a chicken embryo model and a rat model. In future work we also plan to encapsulate cancer drugs such as doxorubicin within the NIR fluorescent HSA nanoparticles for both colon cancer imaging and therapy. - Highlights: ► Near IR human serum albumin nanoparticles were synthesized and characterized. ► Nanoparticles were shown to be physically and chemically stable and photostable. ► Tumor-targeting ligands were covalently conjugated to the nanoparticles. ► Specific colon cancer tumor detection was demonstrated in chicken-embryo and rat models.

  20. The anti-cancer effect of octagon and spherical silver nanoparticles on MCF-7 breast cancer cell line

    Mehrdad Khatami

    2017-04-01

    Full Text Available Background: The modern science of nanotechnology is an interdisciplinary science that has contributed to advances in cancer treatment. This study was performed to evaluate the therapeutic effects of biosynthesized silver nanoparticles on breast cancer cell of line MCF-7 in vitro. Methods: This analytical study was performed in Kerman and Bam University of Medical Sciences, Bam City, Kerman Province, Iran from March 2015 to March 2016. Silver nanoparticles suspension was synthesized using palm kernel extract. The resulting silver nanoparticles were studied and characterized. The ultraviolet-visible spectroscopy and transmission electron microscopy used for screening of physicochemical properties. The average particle size of the biosynthesized silver nanoparticles was determined by transmission electron microscopy. The properties of different concentrations of synthesized silver nanoparticles (1 to 3 μg/ml and palm kernel extract (containing the same concentration of the extract was used for the synthesis of silver nanoparticles against MCF-7 human breast cancer cells were determined by MTT assay. MTT is used to assess cell viability as a function of redox potential. Actively respiring cells convert the water-soluble MTT to an insoluble purple formazan. Results: The ultraviolet-visible spectroscopy showed strong absorption peak at 429 nm. The X-ray diffraction (XRD and transmission electron microscopy (TEM images revealed the formation of silver nanoparticles with spherical and octagon shape and sizes in the range between 1-40 nm, with an average size approximately 17 nm. The anti-cancer effect of silver nanoparticles on cell viability was strongly depends on the concentration of silver nanoparticles and greatly decrease with increasing the concentration of silver nanoparticles. The IC50 amount of silver nanoparticle was 2 μg/ml. Conclusion: The biosynthesized silver nanoparticles showed a dose-dependent toxicity against MCF-7 human breast

  1. Cancer-selective, single agent chemoradiosensitising gold nanoparticles

    Grellet, Sophie; Tzelepi, Konstantina; Roskamp, Meike; Williams, Phil; Sharif, Aquila; Slade-Carter, Richard; Goldie, Peter; Whilde, Nicky; Śmiałek, Małgorzata A.; Mason, Nigel J.

    2017-01-01

    Two nanometre gold nanoparticles (AuNPs), bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine), were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics. PMID:28700660

  2. Cancer-selective, single agent chemoradiosensitising gold nanoparticles.

    Sophie Grellet

    Full Text Available Two nanometre gold nanoparticles (AuNPs, bearing sugar moieties and/or thiol-polyethylene glycol-amine (PEG-amine, were synthesised and evaluated for their in vitro toxicity and ability to radiosensitise cells with 220 kV and 6 MV X-rays, using four cell lines representing normal and cancerous skin and breast tissues. Acute 3 h exposure of cells to AuNPs, bearing PEG-amine only or a 50:50 ratio of alpha-galactose derivative and PEG-amine resulted in selective uptake and toxicity towards cancer cells at unprecedentedly low nanomolar concentrations. Chemotoxicity was prevented by co-administration of N-acetyl cysteine antioxidant, or partially prevented by the caspase inhibitor Z-VAD-FMK. In addition to their intrinsic cancer-selective chemotoxicity, these AuNPs acted as radiosensitisers in combination with 220 kV or 6 MV X-rays. The ability of AuNPs bearing simple ligands to act as cancer-selective chemoradiosensitisers at low concentrations is a novel discovery that holds great promise in developing low-cost cancer nanotherapeutics.

  3. Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

    Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

    2004-01-01

    Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external

  4. NanoParticle Ontology for Cancer Nanotechnology Research

    Thomas, Dennis G.; Pappu, Rohit V.; Baker, Nathan A.

    2010-01-01

    Data generated from cancer nanotechnology research are so diverse and large in volume that it is difficult to share and efficiently use them without informatics tools. In particular, ontologies that provide a unifying knowledge framework for annotating the data are required to facilitate the semantic integration, knowledge-based searching, unambiguous interpretation, mining and inferencing of the data using informatics methods. In this paper, we discuss the design and development of NanoParticle Ontology (NPO), which is developed within the framework of the Basic Formal Ontology (BFO), and implemented in the Ontology Web Language (OWL) using well-defined ontology design principles. The NPO was developed to represent knowledge underlying the preparation, chemical composition, and characterization of nanomaterials involved in cancer research. Public releases of the NPO are available through BioPortal website, maintained by the National Center for Biomedical Ontology. Mechanisms for editorial and governance processes are being developed for the maintenance, review, and growth of the NPO. PMID:20211274

  5. Porous silicon nanoparticles for cancer photothermotherapy

    Zheng Hongmei

    2011-01-01

    Full Text Available Abstract The in vitro cell tests and in vivo animal tests were performed to investigate the feasibility of the photothermal therapy based on porous silicon (PSi in combination with near-infrared (NIR laser. According to the Annexin V- fluorescein isothiocyanate Apoptosis assay test results, the untreated cells and the cells exposed to NIR laser without PSi treatment had a cell viability of 95.6 and 91.3%, respectively. Likewise, the cells treated with PSi but not with NIR irradiation also had a cell viability of 74.4%. Combination of these two techniques, however, showed a cell viability of 6.7%. Also, the cell deaths were mostly due to necrosis but partly due to late apoptosis. The in vivo animal test results showed that the Murine colon carcinoma (CT-26 tumors were completely resorbed without nearly giving damage to surrounding healthy tissue within 5 days of PSi and NIR laser treatment. Tumors have not recurred at all in the PSi/NIR treatment groups thereafter. Both the in vitro cell test and in vivo animal test results suggest that thermotherapy based on PSi in combination with NIR laser irradiation is an efficient technique to selectively destroy cancer cells without damaging the surrounding healthy cells.

  6. Review: Application of Nanoparticles in Urothelial Cancer of the Urinary Bladder

    Chen, Chieh-Hsiao; Chan, Tzu-Min; Wu, Yi-Jhen; Chen, Jia-Jin

    2015-01-01

    Bladder cancer is a common malignancy of the urinary tract, which generally develops in the epithelial lining of the urinary bladder. The specific course of treatment depends on the stage of bladder cancer; however, therapeutic strategies typically involve intravesical drug delivery to reduce toxicity and increase therapeutic effects. Recently, metallic, polymeric, lipid, and protein nanoparticles have been introduced to aid in the treatment of bladder cancer. Nanoparticles are also commonly ...

  7. Nanoparticle-mediated delivery of suicide genes in cancer therapy.

    Vago, Riccardo; Collico, Veronica; Zuppone, Stefania; Prosperi, Davide; Colombo, Miriam

    2016-09-01

    Conventional chemotherapeutics have been employed in cancer treatment for decades due to their efficacy in killing the malignant cells, but the other side of the coin showed off-target effects, onset of drug resistance and recurrences. To overcome these limitations, different approaches have been investigated and suicide gene therapy has emerged as a promising alternative. This approach consists in the introduction of genetic materials into cancerous cells or the surrounding tissue to cause cell death or retard the growth of the tumor mass. Despite promising results obtained both in vitro and in vivo, this innovative approach has been limited, for long time, to the treatment of localized tumors, due to the suboptimal efficiency in introducing suicide genes into cancer cells. Nanoparticles represent a valuable non-viral delivery system to protect drugs in the bloodstream, to improve biodistribution, and to limit side effects by achieving target selectivity through surface ligands. In this scenario, the real potential of suicide genes can be translated into clinically viable treatments for patients. In the present review, we summarize the recent advances of inorganic nanoparticles as non-viral vectors in terms of therapeutic efficacy, targeting capacity and safety issues. We describe the main suicide genes currently used in therapy, with particular emphasis on toxin-encoding genes of bacterial and plant origin. In addition, we discuss the relevance of molecular targeting and tumor-restricted expression to improve treatment specificity to cancer tissue. Finally, we analyze the main clinical applications, limitations and future perspectives of suicide gene therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Ultrasonic system for hyperthermia

    Seppi, E.J.; Shapiro, E.G.; Zitelli, L.T.

    1985-01-01

    A system using ultrasound has been developed for hyperthermia application. It consists of a water bed containing a large ultrasound transducer array for heat application, an annular imaging transducer for alignment and treatment monitoring, and a 30-channel monitoring system for invasive temperature measurements. The heat applicator array contains 30 transducers mounted in a hexagonal configuration. Four subsets of transducers in the array can be remotely mechanically driven in such a way as to allow control of the distribution and diameter of ultrasound power at the effective focus of the array. The array can be remotely translated in three dimensions and can be rotated about its axis of symmetry. These motions allow positioning of the focal area of the array at the desired location. Each transducer of the array is powered by an individual amplifier and can be controlled in intensity and phase. The system can operate at variable ultrasound frequencies. An imaging transducer located at the center of the heat applicator array is used to collect data for ultrasound imaging and other purposes. Ultrasound images are displayed along with marks indicating the location of the heat applicator focal region for setup and for monitoring during treatment. The entire system is under computer control. This allows for operator ease in the control of the numerous parameters involved in the operation of the system

  9. Hyperthermia, immunity and metastases

    Lopatin, V.F.

    1983-01-01

    The analysis of literature data concerning local hyperthermia effects shows that temperatures over 41-42 deg C (in the whole tumor volume), causing tumor growth inhibition and cell injury, can change antigenic nature of a malignant tissue. The tumor injured by thermal effect is able probably the full length of time of injured tissue resorption to maintain at a sufficiently high level antitumoral immunity and lay obstacles to emergence of metastases or even cause regression of those tumoral foci which have not been exposed to direct effect of the injuring agent. The facts of tumoral foci regression take place also upon radiation effect which is associated as well with participation of immune mechanisms. In.experiments with animals an essential increase of immunogenic character of malignant cells exposed to ionizing radiation effect has been observed. It follows that radiation injury of tumoral tissue as well as thermal one is able to stimulate antitumoral immunity and reduce the probability of emergence of metastases. But in case of radiotherapy immunosuppression effect of ionizing radiation (at the expense of inhibition of proliferation and death of immunocompetent cells) can essentially overlap immunostimulating effect related to the changes in antigenic character of tumoral cells

  10. Clinical study of suppository delivery of 5-fluorouracil and pathological effects on metastatic lymph nodes caused by preoperative combined treatment with radiation, intraluminal hyperthermia and 5-fluorouracil suppository in rectal cancer

    Tamura, Takaaki [Kyoto Prefectural Univ. of Medicine (Japan)

    1997-11-01

    Preoperative combined treatment with radiation, intraluminal hyperthermia, and 5-fluorouracil (5-FU) suppository has been reported effective in shrinking locally advanced rectal cancers and facilitating subsequent surgery. Suppository and intravenous 5-FU administration were compared with respect to tissue concentrations in rectal cancer cases. Just before the operation patients received 100 mg of 5-FU via suppository or intravenously. Portal and systemic blood, tumor tissue, normal mucosa and muscle layer separately at 5, 10, 15 cm in the oral direction from the tumor and the pararectal lymph node were harvested for high-performance liquid chromatography determination of 5-FU concentrations. Rectal 5-FU concentrations were significantly higher in the suppository cases compared with the intravenously administrated ones. Suppository distributed more 5-FU at pararectal lymph nodes than intravenous injection. This fact revealed 5-FU suppositories to be a useful drug delivery system for rectal cancer. The pathological effects on metastatic lymph nodes caused by combined treatment were evaluated in 22 cases. Normal lymph nodes showed congestion only. Fibrotic and necrotic changes were characteristic of damaged metastatic areas. In 6 cases (27.3%), no metastatic cells were detected on fibrotically changed areas. The down staging of the lymph node metastatic factor was carried out by preoperative combined treatment. High concentrations of 5-FU at mucosa could suggest the usefulness of 5-FU suppository administration just before operation for prevention of suture-line implantation. (author)

  11. Clinical study of suppository delivery of 5-fluorouracil and pathological effects on metastatic lymph nodes caused by preoperative combined treatment with radiation, intraluminal hyperthermia and 5-fluorouracil suppository in rectal cancer

    Tamura, Takaaki

    1997-01-01

    Preoperative combined treatment with radiation, intraluminal hyperthermia, and 5-fluorouracil (5-FU) suppository has been reported effective in shrinking locally advanced rectal cancers and facilitating subsequent surgery. Suppository and intravenous 5-FU administration were compared with respect to tissue concentrations in rectal cancer cases. Just before the operation patients received 100 mg of 5-FU via suppository or intravenously. Portal and systemic blood, tumor tissue, normal mucosa and muscle layer separately at 5, 10, 15 cm in the oral direction from the tumor and the pararectal lymph node were harvested for high-performance liquid chromatography determination of 5-FU concentrations. Rectal 5-FU concentrations were significantly higher in the suppository cases compared with the intravenously administrated ones. Suppository distributed more 5-FU at pararectal lymph nodes than intravenous injection. This fact revealed 5-FU suppositories to be a useful drug delivery system for rectal cancer. The pathological effects on metastatic lymph nodes caused by combined treatment were evaluated in 22 cases. Normal lymph nodes showed congestion only. Fibrotic and necrotic changes were characteristic of damaged metastatic areas. In 6 cases (27.3%), no metastatic cells were detected on fibrotically changed areas. The down staging of the lymph node metastatic factor was carried out by preoperative combined treatment. High concentrations of 5-FU at mucosa could suggest the usefulness of 5-FU suppository administration just before operation for prevention of suture-line implantation. (author)

  12. Non-Invasive Radiofrequency Field Treatment to Produce Hepatic Hyperthermia: Efficacy and Safety in Swine

    ,; ,; ,; ,; ,; ,; ,; ,; ,

    2017-01-01

    The Kanzius non-invasive radio-frequency hyperthermia system (KNiRFH) has been investigated as a treatment option for hepatic hyperthermia cancer therapy. The treatment involves exposing the patient to an external high-power RF (13.56 MHz) electric field, whereby the propagating waves penetrate deep into the tumor causing targeted heating based on differential tissue dielectric properties. However, a comprehensive examination of the Kanzius system alongside any associated toxicities and its a...

  13. Multifunctional Polymer Nanoparticles for Dual Drug Release and Cancer Cell Targeting

    Yu-Han Wen

    2017-06-01

    Full Text Available Multifunctional polymer nanoparticles have been developed for cancer treatment because they could be easily designed to target cancer cells and to enhance therapeutic efficacy according to cancer hallmarks. In this study, we synthesized a pH-sensitive polymer, poly(methacrylic acid-co-histidine/doxorubicin/biotin (HBD in which doxorubicin (DOX was conjugated by a hydrazone bond to encapsulate an immunotherapy drug, imiquimod (IMQ, to form dual cancer-targeting and dual drug-loaded nanoparticles. At low pH, polymeric nanoparticles could disrupt and simultaneously release DOX and IMQ. Our experimental results show that the nanoparticles exhibited pH-dependent drug release behavior and had an ability to target cancer cells via biotin and protonated histidine.

  14. Applications of nanoparticles in cancer detection and diagnostic tool for hepatocellular carcinoma

    Venkatasalam, C.; Nagappan, A.

    2012-01-01

    Cancer nanotechnology is multidisciplinary area of science and technology. In recent days nano particles are used in medical field as diagnostic tools. It is highly precious and accurate measurement tools for detecting many disease. One of the broad application of cancer biology, for detecting molecular imaging, molecular diagnosis of cancer cells. In the present study deals with the nanoparticles are widely used for finding tumor as biomarker imaging for cancer detection and the nanoparticles are have important notice. An ample choice of materials may be used for construct nanoparticles that can cover for increase the capability of delivery or to provide unique structural and electrical properties for imaging. This exclusive properties are worn to several functional nanoparticles have already been demonstrated, including some clinically approved liposome drugs and metallic imaging agents. In early detection of heptocellular carcinoma, the metallic nanoparticles are vital role in the imaging technology. Several functions of nanoparticles that may eventually additional the understanding of producing imaging especially the darkening and enlarging of the images. These nanoparticles may be able to identify malignant cells by means of molecular detection, visualization of their location in the body by providing enhanced contrast in medical imaging technology, Through selective particle targeting and monitoring of identification of multiplied cells in different organs of the body. In the future prospective of medical field, the nanoparticles are having vital role for detecting cancer cells. (author)

  15. Design of a temperature measurement and feedback control system based on an improved magnetic nanoparticle thermometer

    Du, Zhongzhou; Sun, Yi; Liu, Jie; Su, Rijian; Yang, Ming; Li, Nana; Gan, Yong; Ye, Na

    2018-04-01

    Magnetic fluid hyperthermia, as a novel cancer treatment, requires precise temperature control at 315 K-319 K (42 °C-46 °C). However, the traditional temperature measurement method cannot obtain the real-time temperature in vivo, resulting in a lack of temperature feedback during the heating process. In this study, the feasibility of temperature measurement and feedback control using magnetic nanoparticles is proposed and demonstrated. This technique could be applied in hyperthermia. Specifically, the triangular-wave temperature measurement method is improved by reconstructing the original magnetization response of magnetic nanoparticles based on a digital phase-sensitive detection algorithm. The standard deviation of the temperature in the magnetic nanoparticle thermometer is about 0.1256 K. In experiments, the temperature fluctuation of the temperature measurement and feedback control system using magnetic nanoparticles is less than 0.5 K at the expected temperature of 315 K. This shows the feasibility of the temperature measurement method for temperature control. The method provides a new solution for temperature measurement and feedback control in hyperthermia.

  16. Development and characterization of multifunctional nanoparticles for drug delivery to cancer cells

    Nahire, Rahul Rajaram

    Lipid and polymeric nanoparticles, although proven to be effective drug delivery systems compared to free drugs, have shown considerable limitations pertaining to their uptake and release at tumor sites. Spatial and temporal control over the delivery of anticancer drugs has always been challenge to drug delivery scientists. Here, we have developed and characterized multifunctional nanoparticles (liposomes and polymersomes) which are targeted specifically to cancer cells, and release their contents with tumor specific internal triggers. To enable these nanoparticles to be tracked in blood circulation, we have imparted them with echogenic characteristic. Echogenicity of nanoparticles is evaluated using ultrasound scattering and imaging experiments. Nanoparticles demonstrated effective release with internal triggers such as elevated levels of MMP-9 enzyme found in the extracellular matrix of tumor cells, decreased pH of lysosome, and differential concentration of reducing agents in cytosol of cancer cells. We have also successfully demonstrated the sensitivity of these particles towards ultrasound to further enhance the release with internal triggers. To ensure the selective uptake by folate receptor- overexpressing cancer cells, we decorated these nanoparticles with folic acid on their surface. Fluorescence microscopic images showed significantly higher uptake of folate-targeted nanoparticles by MCF-7 (breast cancer) and PANC-1 (pancreatic cancer) cells compared to particles without any targeting ligand on their surface. To demonstrate the effectiveness of these nanoparticles to carry the drugs inside and kill cancer cells, we encapsulated doxorubicin and/or gemcitabine employing the pH gradient method. Drug loaded nanoparticles showed significantly higher killing of the cancer cells compared to their non-targeted counterparts and free drugs. With further development, these nanoparticles certainly have potential to be used as a multifunctional nanocarriers for image

  17. A thermocouple thermometry system for ultrasound hyperthermia

    Ozarka, M.; Gharakhani, A.; Magin, R.; Cain, C.

    1984-01-01

    A thermometry system designed to be used in the treatment of cancer by ultrasound hyperthermia is described. The system monitors tumor temperatures using 16 type T (copper-constantan) thermocouples and is controlled by a 12 MHz Intel 8031 microcomputer. An analog circuit board contains the thermocouple amplifiers, an analog multiplexer, scaling circuitry, and an analog to digital converter. A digital board contains the Intel 8031, program memory, data memory, as well as circuitry for control and data communications. Communication with the hyperthermia system control computer is serially by RS-232 with selectable baud rate. Since the thermocouple amplifiers may have slight differences in gain and offset, a calibrated offset is added to a lookup table value to obtain the proper display temperature to within +- 0.1 0 C. The calibration routine, implemented in software, loads a nonvolatile random access memory chip with the proper offset values based on the outputs of each thermocouple channel at known temperatures which bracket a range of interest

  18. Hormonal, Biochemical and Haematological Changes in Response to Acute Hyperthermia in Rabbits

    Zahran, N.A.R.M.

    2004-01-01

    Today, hyperthermia plays a significant role in the evidence-based on treatment of cancer patients. Such promising endeavor is due to the fact that neoplastic cells are more heat sensitive than normal cells. the prospect of using hyperthermia alone to treat cancer tumours is appealing because hyperthermia is a physical treatment and so would have fewer side effects than chemotherapy or radiotherapy and, it could be used in combination with these therapeutic approaches. much more consistent evidence has been obtained experimentally, and continuing clinical interest has been encouraged by confirmation that, at relatively low temperature (37-41.5 C), heat enhances cell growth and may well enhance also the growth and proliferation of tumours, while above 45 C heat begins to damage both normal and malignant cells in both animal and human. So, the goal is to achieve a selective temperature elevation between 42-45 C at the tumour site while maintaining healthy tissue temperatures in a physiological save range.This study was undertaken to investigate the effect of acute whole body hyperthermia , (WBH) (rectal temperature 43 c) on biochemical , hormonal and haematological changes in normal healthy local strain (baladi) rabbits.The thermal late effects (recovery) at 24 hr-post whole body hyperthermia was also undertaken , in the attempt to evaluate the degree of safety , when hyperthermia is applied in the clinic for treating cancer and other diseases

  19. A multicenter study of using carbon nanoparticles to show sentinel lymph nodes in early gastric cancer.

    Yan, Jun; Zheng, Xiaoling; Liu, Zhangyuanzhu; Yu, Jiang; Deng, Zhenwei; Xue, Fangqing; Zheng, Yu; Chen, Feng; Shi, Hong; Chen, Gang; Lu, Jianping; Cai, Lisheng; Cai, Mingzhi; Xiang, Gao; Hong, Yunfeng; Chen, Wenbo; Li, Guoxin

    2016-04-01

    Lymph node metastasis occurs in approximately 10% of early gastric cancer. Preoperative or intra-operative identification of lymph node metastasis in early gastric cancer is crucial for surgical planning. The purpose of this study was to evaluate the feasibility of using carbon nanoparticles to show sentinel lymph nodes (SLNs) in early gastric cancer. A multicenter study was performed between July 2012 and November 2014. Ninety-one patients with early gastric cancer identified by preoperative endoscopic ultrasonography were recruited. One milliliter carbon nanoparticles suspension, which is approved by Chinese Food and Drug Administration, was endoscopically injected into the submucosal layer at four points around the site of the primary tumor 6-12 h before surgery. Laparoscopic radical resection with D2 lymphadenectomy was performed. SLNs were defined as nodes that were black-dyed by carbon nanoparticles in greater omentum and lesser omentum near gastric cancer. Lymph node status and SLNs accuracy were confirmed by pathological analysis. All patients had black-dyed SLNs lying in greater omentum and/or lesser omentum. SLNs were easily found under laparoscopy. The mean number of SLNs was 4 (range 1-9). Carbon nanoparticles were around cancer in specimen. After pathological analysis, 10 patients (10.99%) had lymph node metastasis in 91 patients with early gastric cancer. SLNs were positive in 9 cases and negative in 82 cases. In pathology, carbon nanoparticles were seen in lymphatic vessels, lymphoid sinus, and macrophages in SLNs. When SLNs were positive, cancer cells were seen in lymph nodes. The sensitivity, specificity, and accuracy of black-dyed SLNs in early gastric cancers were 90, 100, and 98.9 %, respectively. No patient had any side effects of carbon nanoparticles in this study. It is feasible to use carbon nanoparticles to show SLNs in early gastric cancer. Carbon nanoparticles suspension is safe for submucosal injection.

  20. Hyperthermia and radiotherapy

    Lindholm, C.E.

    1992-01-01

    Combined hyperthermia (HT 45 min once or twice per week) and low dose radiotherapy (LDRT 30-34.5 Gy in 2-3 weeks) have been given to 182 locally recurrent or metastatic superficial tumours in 133 patients. Tumour response was analysed in 137 tumours in 100 patients. The overall complete response (CR) was 50% with a median duration (DCR) of 13±3 months. When mammary carcinoma, representing 62% of the treated tumours, were analysed, CR was 62% with a DCR of 14±4 months. In a comparative, non-randomized study, on 34 matched tumour pairs in 24 patients, treatment was given with LDRT+HT to the larger and the same LDRT to the smaller tumour, the patients acting as their own control. A significant difference in CR was obtained in favour of the combined treatment (p=0.0013 all diagnosis and p=0.0027 mammary carcinoma). There was no significant difference in DCR between the two modalities. No significant difference in CR was seen when tumours were randomely treated with HT once (CR 56%) or twice (CR 69%) per week combined with the same LDRT. Predictive factors for CR, multivariately analysed (15 parameters), in mammary carcinoma recurring in earlier irradiated regions, were; the present LDRT absorbed dose (p=0.02) and the average minimum temperature in the best HT session (p=0.03). Significant skin toxicity was seen in 28% of all the 182 heated regions. Prognostic factors for skin damage, multivariately analysed, were; the extension of the heated region (p=0.007) and the highest average maximum temperature in any of the HT sessions (p=0.04). Pain was in some way correlated to severe toxicity but was not considered to be an optimal monitor for HT as many patients with severe and moderate pain were without any serious skin reactions, while slight or no pain sometimes were associated with severe reactions. 401 refs

  1. Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

    Ryu, Samuel; Brown, Stephen L.; Kim, Sang-Hie; Khil, Mark S.; Kim, Jae Ho

    1996-01-01

    Purpose: Recent cell culture studies by us and others suggest that some human carcinoma cells are more sensitive to heat than are rodent cells following mild hyperthermia. In studying the cellular mechanism of enhanced thermosensitivity of human tumor cells to hyperthermia, prostatic carcinoma cells of human origin were found to be more sensitive to mild hyperthermia than other human cancer cells. The present study was designed to determine the magnitude of radiosensitization of human prostatic carcinoma cells by mild hyperthermia and to examine whether the thermal radiosensitization is related to the intrinsic thermosensitivity of cancer cells. Methods and Materials: Two human prostatic carcinoma cell lines (DU-145 and PC-3) and other carcinoma cells of human origin, in particular, colon (HT-29), breast (MCF-7), lung (A-549), and brain (U-251) were exposed to temperatures of 40-41 deg. C. Single acute dose rate radiation and fractionated radiation were combined with mild hyperthermia to determine thermal radiosensitization. The end point of the study was the colony-forming ability of single-plated cells. Results: DU-145 and PC-3 cells were found to be exceedingly thermosensitive to 41 deg. C for 24 h, relative to other cancer cell lines. Ninety percent of the prostatic cancer cells were killed by a 24 h heat exposure. Prostatic carcinoma cells exposed to a short duration of heating at 41 deg. C for 2 h resulted in a substantial enhancement of radiation-induced cytotoxicity. The thermal enhancement ratios (TERs) of single acute dose radiation following heat treatment 41 deg. C for 2 h were 2.0 in DU-145 cells and 1.4 in PC-3 cells. The TERs of fractionated irradiation combined with continuous heating at 40 deg. C were similarly in the range of 2.1 to 1.4 in prostate carcinoma cells. No significant radiosensitization was observed in MCF-7 and HT-29 cells under the same conditions. Conclusion: The present data suggest that a significant radiosensitization of

  2. Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells

    Marina Pöttler

    2015-11-01

    Full Text Available Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5 were treated with SPIONs, either coated with lauric acid (SEONLA only, or additionally with a protein corona of bovine serum albumin (BSA; SEONLA-BSA, or with dextran (SEONDEX. Both micronuclei testing and the detection of γH2A.X revealed no genotoxic effects of SEONLA-BSA, SEONDEX or SEONLA. Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system.

  3. Magnetomotive Optical Coherence Elastography for Magnetic Hyperthermia Dosimetry Based on Dynamic Tissue Biomechanics

    Huang, Pin-Chieh; Pande, Paritosh; Ahmad, Adeel; Marjanovic, Marina; Spillman, Darold R.; Odintsov, Boris; Boppart, Stephen A.

    2016-01-01

    Magnetic nanoparticles (MNPs) have been used in many diagnostic and therapeutic biomedical applications over the past few decades to enhance imaging contrast, steer drugs to targets, and treat tumors via hyperthermia. Optical coherence tomography (OCT) is an optical biomedical imaging modality that relies on the detection of backscattered light to generate high-resolution cross-sectional images of biological tissue. MNPs have been utilized as imaging contrast and perturbative mechanical agents in OCT in techniques called magnetomotive OCT (MM-OCT) and magnetomotive elastography (MM-OCE), respectively. MNPs have also been independently used for magnetic hyperthermia treatments, enabling therapeutic functions such as killing tumor cells. It is well known that the localized tissue heating during hyperthermia treatments result in a change in the biomechanical properties of the tissue. Therefore, we propose a novel dosimetric technique for hyperthermia treatment based on the viscoelasticity change detected by MM-OCE, further enabling the theranostic function of MNPs. In this paper, we first review the basic principles and applications of MM-OCT, MM-OCE, and magnetic hyperthermia, and present new preliminary results supporting the concept of MM-OCE-based hyperthermia dosimetry. PMID:28163565

  4. Ultrastable Nontoxic RNA Nanoparticles for Targeting Triple-Negative Breast Cancer Stem Cells

    2016-04-01

    of the 20-F modified 3WJ-EGFRapt/ anti-miR-21 nanoparticles was studied using the TGGE system (Biometra GmbH, Germany ). One of the fragments (c3WJ...MicroRNA Gene Expression Deregulation in Human Breast Cancer. Cancer Res. 2005, 65, 7065–7070. 8. Croce, C. M.; Calin, G. A. MiRNAs, Cancer, and Stem Cell

  5. Comparative cytotoxic response of nickel ferrite nanoparticles in human liver HepG2 and breast MFC-7 cancer cells.

    Ahamed, Maqusood; Akhtar, Mohd Javed; Alhadlaq, Hisham A; Khan, M A Majeed; Alrokayan, Salman A

    2015-09-01

    Nickel ferrite nanoparticles (NPs) have received much attention for their potential applications in biomedical fields such as magnetic resonance imaging, drug delivery and cancer hyperthermia. However, little is known about the toxicity of nickel ferrite NPs at the cellular and molecular levels. In this study, we investigated the cytotoxic responses of nickel ferrite NPs in two different types of human cells (i.e., liver HepG2 and breast MCF-7). Nickel ferrite NPs induced dose-dependent cytotoxicity in both types of cells, which was demonstrated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT), neutral red uptake (NRU) and lactate dehydrogenase (LDH) assays. Nickel ferrite NPs were also found to induce oxidative stress, which was evident by the depletion of glutathione and the induction of reactive oxygen species (ROS) and lipid peroxidation. The mitochondrial membrane potential due to nickel ferrite NP exposure was also observed. The mRNA levels for the tumor suppressor gene p53 and the apoptotic genes bax, CASP3 and CASP9 were up-regulated, while the anti-apoptotic gene bcl-2 was down-regulated following nickel ferrite NP exposure. Furthermore, the activities of apoptotic enzymes (caspase-3 and caspase-9) were also higher in both types of cells treated with nickel ferrite NPs. Cytotoxicity induced by nickel ferrite was efficiently prevented by N-acetyl cysteine (ROS scavenger) treatment, which suggested that oxidative stress might be one of the possible mechanisms of nickel ferrite NP toxicity. We also observed that MCF-7 cells were slightly more susceptible to nickel ferrite NP exposure than HepG2 cells. This study warrants further investigation to explore the potential mechanisms of different cytotoxic responses of nickel ferrite NPs in different cell lines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Simple and Rapid Synthesis of Magnetite/Hydroxyapatite Composites for Hyperthermia Treatments via a Mechanochemical Route

    Iwasaki, Tomohiro; Nakatsuka, Ryo; Murase, Kenya; Takata, Hiroshige; Nakamura, Hideya; Watano, Satoru

    2013-01-01

    This paper presents a simple method for the rapid synthesis of magnetite/hydroxyapatite composite particles. In this method, superparamagnetic magnetite nanoparticles are first synthesized by coprecipitation using ferrous chloride and ferric chloride. Immediately following the synthesis, carbonate-substituted (B-type) hydroxyapatite particles are mechanochemically synthesized by wet milling dicalcium phosphate dihydrate and calcium carbonate in a dispersed suspension of magnetite nanoparticles, during which the magnetite nanoparticles are incorporated into the hydroxyapatite matrix. We observed that the resultant magnetite/hydroxyapatite composites possessed a homogeneous dispersion of magnetite nanoparticles, characterized by an absence of large aggregates. When this material was subjected to an alternating magnetic field, the heat generated increased with increasing magnetite concentration. For a magnetite concentration of 30 mass%, a temperature increase greater than 20 K was achieved in less than 50 s. These results suggest that our composites exhibit good hyperthermia properties and are promising candidates for hyperthermia treatments. PMID:23629669

  7. Simple and Rapid Synthesis of Magnetite/Hydroxyapatite Composites for Hyperthermia Treatments via a Mechanochemical Route

    Tomohiro Iwasaki

    2013-04-01

    Full Text Available This paper presents a simple method for the rapid synthesis of magnetite/hydroxyapatite composite particles. In this method, superparamagnetic magnetite nanoparticles are first synthesized by coprecipitation using ferrous chloride and ferric chloride. Immediately following the synthesis, carbonate-substituted (B-type hydroxyapatite particles are mechanochemically synthesized by wet milling dicalcium phosphate dihydrate and calcium carbonate in a dispersed suspension of magnetite nanoparticles, during which the magnetite nanoparticles are incorporated into the hydroxyapatite matrix. We observed that the resultant magnetite/hydroxyapatite composites possessed a homogeneous dispersion of magnetite nanoparticles, characterized by an absence of large aggregates. When this material was subjected to an alternating magnetic field, the heat generated increased with increasing magnetite concentration. For a magnetite concentration of 30 mass%, a temperature increase greater than 20 K was achieved in less than 50 s. These results suggest that our composites exhibit good hyperthermia properties and are promising candidates for hyperthermia treatments.

  8. silver nanoparticles on liver cancer cells (HepG2

    Ahmed I. El-Batal

    2018-01-01

    Full Text Available This study demonstrates a novel approach for the synthesis of silver nanoparticles (AgNPs against human liver cancer cell line (HepG2 using prodigiosin pigment isolated from Serratia marcescens. It further investigates the influence of various parameters such as initial pH, temperature, silver nitrate (AgNO 3 concentration, and prodigiosin concentration on stability and optical properties of synthesized prodigiosin AgNPs. Highly stable, spherical prodigiosin-conjugated AgNPs were synthesized with a mean diameter of 9.98 nm using a rapid one-step method. The cytotoxic activity investigated in the present study indicated that prodigiosin and prodigiosin-conjugated AgNPs possessed a strong cytotoxic potency against human liver cancer. The In silico molecular docking results of prodigiosin and prodigiosin-conjugated AgNPs are congruent with the In vitro studies and these AgNPs can be considered as good inhibitors of mitogen-activated protein kinase 1 (MEK kinases. The study opened the possibility of using prodigiosin-conjugated AgNPs to increase the efficiency of liver cancer treatment.

  9. Cytotoxic Effect on Cancerous Cell Lines by Biologically Synthesized Silver Nanoparticles

    Balaji Kulandaivelu

    Full Text Available The biosynthesis of nanoparticles has been proposed as an environmental friendly and cost effective alternative to chemical and physical methods. Silver nanoparticles are biologically synthesized and characterized were used in the study. The invitro cytotoxic effect of biologically synthesized silver nanoparticles against MCF-7 cancer cell lines were assessed. The cytotoxic effects of the silver nanoparticles could significantly inhibited MCF-7 cancer cell lines proliferation in a time and concentration-dependent manner by MTT assay. Acridine orange, ethidium bromide (AO/EB dual staining, caspase-3 and DNA fragmentation assays were carried out using various concentrations of silver nanoparticles ranging from 1 to 100 μg/mL. At 100 μg/mL concentration, the silver nanoparticles exhibited significant cytotoxic effects and the apoptotic features were confirmed through caspase-3 activation and DNA fragmentation assays. Western blot analysis has revealed that nanoparticle was able to induce cytochrome c release from the mitochondria, which was initiated by the inhibition of Bcl-2 and activation of Bax. Thus, the results of the present study indicate that biologically synthesized silver nanoparticles might be used to treat breast cancer. The present studies suggest that these nanoparticles could be a new potential adjuvant chemotherapeutic and chemo preventive agent against cytotoxic cells. However, it necessitates clinical studies to ascertain their potential as anticancer agents.

  10. Regional hyperthermia of the liver

    Petrovich, Z.; Langholz, B.; Astrahan, M.; Emami, B.; Oleson, J.R.

    1989-01-01

    From 1981 through 1986, 49 patients with metastatic liver tumors received deep regional hyperthermia in phase I protocols in six major medical centers in the United States. Adenocarcinoma was seen in 80% of patients with colon as the primary site in 26%. The remaining patients had the following histological diagnoses: Soft tissue sarcoma in seven, malignant melanoma in two and transitional cell carcinoma in one. Deep regional hyperthermia treatments with a BSD-1000 annular phased array were given once or twice a week with a total of 167 treatment sessions, mean 3.4 (range 1 to 8). In addition to deep regional hyperthermia, 17 patients received radiotherapy, and 14 received chemotherapy. The median survival for all patients was 25 weeks. Complete response was obtained in two patients and partial response in four patients. An additional ten patients had nominal response. There was no complete or partial response among the 14 hyperthermia alone treated patients. Of the 26 patients who presented with severe pain, five had complete pain relief, five had partial relief and the majority had a lesser degree of pain relief or no pain relief. Acute treatment toxicity consisted of pain in ten, systemic temperature increase to 39 0 C in four tachycardia in two, claustrophobia in one. The majority of patients did not experience acute toxicity. No late toxicity was recorded in this group of 49 patients. (orig./MG)

  11. Eight-MHz RF-hyperthermia for advanced urological malignancies

    Hisazumi, Haruo; Nakajima, Kazuyoshi

    1986-01-01

    Eight-MHz radiofrequency hyperthermia (H) using a Thermotron-RF Model 8, and its combination with irradiation (RH), anticancer drugs (CH) or anticancer drugs plus irradiation (CRH), were carried out for a total of 48 urological malignancies: 10 cases of renal cancer, 1 of renal pelvic cancer, 2 of uretetral cancer, 19 of bladder cancer, 5 of prostatic cancer, 9 of metastatic lesion of urological cancers and 2 of other urological cancers. All had failed in previous treatments, or had not undergone surgery because of their poor general condition. Four cases, including 2 of bladder cancer, 1 of prostatic cancer and 1 of metastatic lesion of bladder cancer, were treated with H. Twenty-five cases, including 3 renal cancer cases, were treated with RH. Seven of the 10 cases of renal cancer were treated with mitomycin C-microcapsule embolization prior to RH (CRH). Twelve of the 23 cases with urothelial cancer or its metastasis, including 1 of renal pelvic cancer, 10 of bladder cancer and 1 of metastatic lesion of bladder cancer, received combined treatment of THP-adriamycin, one of the derivatives of adriamycin, by i.v. and RF-heating (CH). Hyperthermia was given twice a week, totalling 10 sessions in 5 weeks. Intratumoral temperature was kept above 42.5 deg C for 30 to 40 minutes during one-hour heating. Complete tumor disappearance was obtained in the 5 bladder cancer cases. Partial tumor regression, defined as a regression of 50 % or more, was obtained in 11 cases. As side effects, mild skin burns and anorexia were observed in approximately 30 to 40 % of cases. Seven obese cases, who had subcutaneous tissue 15 mm thick or more, developed fat tissue induration after treatment. (author)

  12. Theranostic Iron Oxide/Gold Ion Nanoprobes for MR Imaging and Noninvasive RF Hyperthermia.

    Fazal, Sajid; Paul-Prasanth, Bindhu; Nair, Shantikumar V; Menon, Deepthy

    2017-08-30

    This work focuses on the development of a nanoparticulate system that can be used for magnetic resonance (MR) imaging and E-field noninvasive radiofrequency (RF) hyperthermia. For this purpose, an amine-functional gold ion complex (GIC), [Au(III)(diethylenetriamine)Cl]Cl 2 , which generates heat upon RF exposure, was conjugated to carboxyl-functional poly(acrylic acid)-capped iron-oxide nanoparticles (IO-PAA NPs) to form IO-GIC NPs of size ∼100 nm. The multimodal superparamagnetic IO-GIC NPs produced T2-contrast on MR imaging and unlike IO-PAA NPs generated heat on RF exposure. The RF heating response of IO-GIC NPs was found to be dependent on the RF power, exposure period, and particle concentration. IO-GIC NPs at a concentration of 2.5 mg/mL showed a high heating response (δT) of ∼40 °C when exposed to 100 W RF power for 1 min. In vitro cytotoxicity measurements on NIH-3T3 fibroblast cells and 4T1 cancer cells showed that IO-GIC NPs are cytocompatible at high NP concentrations for up to 72 h. Upon in vitro RF exposure (100 W, 1 min), a high thermal response leads to cell death of 4T1 cancer cells incubated with IO-GIC NPs (1 mg/mL). Hematoxylin and eosin imaging of rat liver tissues injected with 100 μL of 2.5 mg/mL IO-GIC NPs and exposed to low RF power of 20 W for 10 min showed significant loss of tissue morphology at the site of injection, as against RF-exposed or nanoparticle-injected controls. In vivo MR imaging and noninvasive RF exposure of 4T1-tumor-bearing mice after IO-GIC NP administration showed T2 contrast enhancement and a localized generation of high temperatures in tumors, leading to tumor tissue damage. Furthermore, the administration of IO-GIC NPs followed by RF exposure showed no adverse acute toxicity effects in vivo. Thus, IO-GIC NPs show good promise as a theranostic agent for magnetic resonance imaging and noninvasive RF hyperthermia for cancer.

  13. Application of gold nanoparticles for gastrointestinal cancer theranostics: A systematic review.

    Singh, Mohan; Harris-Birtill, David C C; Markar, Sheraz R; Hanna, George B; Elson, Daniel S

    2015-11-01

    Gold nanoparticles (GNPs) are readily synthesised structures that absorb light strongly to generate thermal energy which induces photothermal destruction of malignant tissue. This review examines the efficacy, potential challenges and toxicity from in vitro and in vivo applications of GNPs in oesophageal, gastric and colon cancers. A systematic literature search of Medline, Embase, Web of Science and Cochrane databases was performed using PRISMA guidelines. Two hundred and eighty-four papers were reviewed with sixteen studies meeting the inclusion criteria. The application of GNPs in eleven in vivo rodent studies with GI adenocarcinoma demonstrated excellent therapeutic outcomes but poor corroboration in terms of the cancer cells used, photothermal irradiation regimes, fluorophores and types of nanoparticles. There is compelling evidence of the translational potential of GNPs to be complimentary to surgery and feasible in the photothermal therapy of GI cancer but reproducibility and standardisation require development prior to GI cancer clinical trials. Gold nanoparticles are one of the most potentially useful nanoparticles. This is especially true in cancer therapeutics because of their photothermal properties. In this comprehensive article, the authors reviewed the application and efficacy of gold nanoparticles in both the diagnosis and treatment of GI cancers. This review should provide a stimulus for researchers to further develop and translate these nanoparticles into future clinical trials. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

    Kok, H. Petra; Crezee, Johannes; Franken, Nicolaas A.P.; Stalpers, Lukas J.A.; Barendsen, Gerrit W.; Bel, Arjan

    2014-01-01

    Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia. Methods and Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system. The temperature-dependent parameters α (Gy −1 ) and β (Gy −2 ) of the linear–quadratic model for prostate cancer were estimated from the literature. No thermal enhancement was assumed for normal tissue. The intensity modulated radiation therapy plans and temperature distributions were exported to our in-house-developed radiation therapy treatment planning system, APlan, and equivalent dose distributions without hyperthermia were calculated voxel by voxel using the linear–quadratic model. Results: The planned average tumor temperatures T90, T50, and T10 in the planning target volume were 40.5°C, 41.6°C, and 42.4°C, respectively. The planned minimum, mean, and maximum radiation therapy doses were 62.9 Gy, 76.0 Gy, and 81.0 Gy, respectively. Adding hyperthermia yielded an equivalent dose distribution with an extended 95% isodose level. The equivalent minimum, mean, and maximum doses reflecting the radiosensitization by hyperthermia were 70.3 Gy, 86.3 Gy, and 93.6 Gy, respectively, for a linear increase of α with temperature. This can be considered similar to a dose escalation with a substantial increase in tumor control probability for high-risk prostate carcinoma. Conclusion: A model to quantify the effect of combined radiation therapy and hyperthermia in terms of equivalent dose distributions was presented. This model is particularly instructive to estimate the potential effects of interaction from different treatment

  15. Can we settle with single-band radiometric temperature monitoring during hyperthermia treatment of chestwall recurrence of breast cancer using a dual-mode transceiving applicator?

    Jacobsen, Svein [Electrical Engineering Group, Department of Physics and Technology, Faculty of Science, University of Tromsoe, N-9037 Tromsoe (Norway); Stauffer, Paul R [Radiation Oncology Department, University of California at San Francisco, San Francisco, CA 94143 (United States)

    2007-02-21

    The total thermal dose that can be delivered during hyperthermia treatments is frequently limited by temperature heterogeneities in the heated tissue volume. Reliable temperature information on the heated area is thus vital for the optimization of clinical dosimetry. Microwave radiometry has been proposed as an accurate, quick and painless temperature sensing technique for biological tissue. Advantages include the ability to sense volume-averaged temperatures from subsurface tissue non-invasively, rather than with a limited set of point measurements typical of implanted temperature probes. We present a procedure to estimate the maximum tissue temperature from a single radiometric brightness temperature which is based on a numerical simulation of 3D tissue temperature distributions induced by microwave heating at 915 MHz. The temperature retrieval scheme is evaluated against errors arising from unknown variations in thermal, electromagnetic and design model parameters. Whereas realistic deviations from base values of dielectric and thermal parameters have only marginal impact on performance, pronounced deviations in estimated maximum tissue temperature are observed for unanticipated variations of the temperature or thickness of the bolus compartment. The need to pay particular attention to these latter applicator construction parameters in future clinical implementation of the thermometric method is emphasized.

  16. Can we settle with single-band radiometric temperature monitoring during hyperthermia treatment of chestwall recurrence of breast cancer using a dual-mode transceiving applicator?

    Jacobsen, Svein; Stauffer, Paul R

    2007-01-01

    The total thermal dose that can be delivered during hyperthermia treatments is frequently limited by temperature heterogeneities in the heated tissue volume. Reliable temperature information on the heated area is thus vital for the optimization of clinical dosimetry. Microwave radiometry has been proposed as an accurate, quick and painless temperature sensing technique for biological tissue. Advantages include the ability to sense volume-averaged temperatures from subsurface tissue non-invasively, rather than with a limited set of point measurements typical of implanted temperature probes. We present a procedure to estimate the maximum tissue temperature from a single radiometric brightness temperature which is based on a numerical simulation of 3D tissue temperature distributions induced by microwave heating at 915 MHz. The temperature retrieval scheme is evaluated against errors arising from unknown variations in thermal, electromagnetic and design model parameters. Whereas realistic deviations from base values of dielectric and thermal parameters have only marginal impact on performance, pronounced deviations in estimated maximum tissue temperature are observed for unanticipated variations of the temperature or thickness of the bolus compartment. The need to pay particular attention to these latter applicator construction parameters in future clinical implementation of the thermometric method is emphasized

  17. CCR 20th Anniversary Commentary: Prospects and Challenges of Therapeutic Nanoparticles in Cancer.

    Rahman, Mohammad Aminur; Shin, Dong M

    2015-10-15

    In their review article published in the March 1, 2008, issue of Clinical Cancer Research, Cho and colleagues presented the strong potential of nanotechnology in cancer. This commentary discusses the latest advances in nanotechnology, which provide novel approaches for cancer diagnosis, imaging, drug delivery, and personalized therapy; highlights the perspectives for therapeutic nanoparticles; and describes the advantages and challenges of their multifunctionalities. ©2015 American Association for Cancer Research.

  18. Riboflavin photoactivation by upconversion nanoparticles for cancer treatment

    Khaydukov, E. V.; Mironova, K. E.; Semchishen, V. A.; Generalova, A. N.; Nechaev, A. V.; Khochenkov, D. A.; Stepanova, E. V.; Lebedev, O. I.; Zvyagin, A. V.; Deyev, S. M.; Panchenko, V. Ya.

    2016-10-01

    Riboflavin (Rf) is a vitamin and endogenous photosensitizer capable to generate reactive oxygen species (ROS) under UV-blue irradiation and kill cancer cells, which are characterized by the enhanced uptake of Rf. We confirmed its phototoxicity on human breast adenocarcinoma cells SK-BR-3 preincubated with 30-μM Rf and irradiated with ultraviolet light, and proved that such Rf concentrations (60 μM) are attainable in vivo in tumour site by systemic intravascular injection. In order to extend the Rf photosensitization depth in cancer tissue to 6 mm in depth, we purpose-designed core/shell upconversion nanoparticles (UCNPs, NaYF4:Yb3+:Tm3+/NaYF4) capable to convert 2% of the deeply-penetrating excitation at 975 nm to ultraviolet-blue power. This power was expended to photosensitise Rf and kill SK-BR-3 cells preincubated with UCNPs and Rf, where the UCNP-Rf energy transfer was photon-mediated with ~14% Förster process contribution. SK-BR-3 xenograft regression in mice was observed for 50 days, following the Rf-UCNPs peritumoural injection and near-infrared light photodynamic treatment of the lesions.

  19. Targeted Therapeutic Nanoparticles: An Immense Promise to Fight against Cancer

    Sheikh Tasnim Jahan

    2017-01-01

    Full Text Available In nanomedicine, targeted therapeutic nanoparticle (NP is a virtual outcome of nanotechnology taking the advantage of cancer propagation pattern. Tying up all elements such as therapeutic or imaging agent, targeting ligand, and cross-linking agent with the NPs is the key concept to deliver the payload selectively where it intends to reach. The microenvironment of tumor tissues in lymphatic vessels can also help targeted NPs to achieve their anticipated accumulation depending on the formulation objectives. This review accumulates the application of poly(lactic-co-glycolic acid (PLGA and polyethylene glycol (PEG based NP systems, with a specific perspective in cancer. Nowadays, PLGA, PEG, or their combinations are the mostly used polymers to serve the purpose of targeted therapeutic NPs. Their unique physicochemical properties along with their biological activities are also discussed. Depending on the biological effects from parameters associated with existing NPs, several advantages and limitations have been explored in teaming up all the essential facts to give birth to targeted therapeutic NPs. Therefore, the current article will provide a comprehensive review of various approaches to fabricate a targeted system to achieve appropriate physicochemical properties. Based on such findings, researchers can realize the benefits and challenges for the next generation of delivery systems.

  20. Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles

    Hanley, Cory; Layne, Janet; Feris, Kevin; Wingett, Denise [Department of Biological Sciences, Boise State University, Boise, ID 83725 (United States); Punnoose, Alex; Reddy, K M; Coombs, Isaac; Coombs, Andrew [Department of Physics, Boise State University, Boise, ID 83725 (United States)], E-mail: denisewingett@boisestate.edu

    2008-07-23

    Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine. Here we examine the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells ({approx}28-35 x) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity, as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. Mechanisms of toxicity appear to involve the generation of reactive oxygen species, with cancerous T cells producing higher inducible levels than normal T cells. In addition, nanoparticles were found to induce apoptosis and the inhibition of reactive oxygen species was found to be protective against nanoparticle induced cell death. The novel findings of cell selective toxicity, towards potential disease causing cells, indicate a potential utility of ZnO nanoparticles in the treatment of cancer and/or autoimmunity.

  1. Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles

    Hanley, Cory; Layne, Janet; Feris, Kevin; Wingett, Denise; Punnoose, Alex; Reddy, K M; Coombs, Isaac; Coombs, Andrew

    2008-01-01

    Nanoparticles are increasingly being recognized for their potential utility in biological applications including nanomedicine. Here we examine the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells (∼28-35 x) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity, as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. Mechanisms of toxicity appear to involve the generation of reactive oxygen species, with cancerous T cells producing higher inducible levels than normal T cells. In addition, nanoparticles were found to induce apoptosis and the inhibition of reactive oxygen species was found to be protective against nanoparticle induced cell death. The novel findings of cell selective toxicity, towards potential disease causing cells, indicate a potential utility of ZnO nanoparticles in the treatment of cancer and/or autoimmunity

  2. Cytotoxic Induction and Photoacoustic Imaging of Breast Cancer Cells Using Astaxanthin-Reduced Gold Nanoparticles

    Subramaniyan Bharathiraja

    2016-04-01

    Full Text Available Astaxanthin, a kind of photosynthetic pigment, was employed for gold nanoparticle formation. Nanoparticles were characterized using Ulteraviolet-Visible (UV-Vis spectroscopy, transmission electron microscopy, and X-ray diffraction, and the possible presence of astaxanthin functional groups were analyzed by Fourier transform infrared spectroscopy (FTIR. The cytotoxic effect of synthesized nanoparticles was evaluated against MDA-MB-231 (human breast cancer cells using a tetrazolium-based assay, and synthesized nanoparticles exhibited dose-dependent toxicity. The morphology upon cell death was differentiated through fluorescent microscopy using different stains that predicted apoptosis. The synthesized nanoparticles were applied in ultrasound-coupled photoacoustic imaging to obtain good images of treated cells. Astaxanthin-reduced gold nanoparticle has the potential to act as a promising agent in the field of photo-based diagnosis and therapy.

  3. Polymeric nanoparticles for the intracellular delivery of paclitaxel in lung and breast cancer

    Zubris, Kimberly Ann Veronica

    Nanoparticles are useful for addressing many of the difficulties encountered when administering therapeutic compounds. Nanoparticles are able to increase the solubility of hydrophobic drugs, improve pharmacokinetics through sustained release, alter biodistribution, protect sensitive drugs from low pH environments or enzymatic alteration, and, in some cases, provide targeting of the drug to the desired tissues. The use of functional nanocarriers can also provide controlled intracellular delivery of a drug. To this end, we have developed functional pH-responsive expansile nanoparticles for the intracellular delivery of paclitaxel. The pH-responsiveness of these nanoparticles occurs due to a hydrophobic to hydrophilic transition of the polymer occurring under mildly acidic conditions. These polymeric nanoparticles were systematically evaluated for the delivery of paclitaxel in vitro and in vivo to improve local therapy for lung and breast cancers. Nanoparticles were synthesized using a miniemulsion polymerization process and were subsequently characterized and found to swell when exposed to acidic environments. Paclitaxel was successfully encapsulated within the nanoparticles, and the particles exhibited drug release at pH 5 but not at pH 7.4. In addition, the uptake of nanoparticles was observed using flow cytometry, and the anticancer efficacy of the paclitaxel-loaded nanoparticles was measured using cancer cell lines in vitro. The potency of the paclitaxel-loaded nanoparticles was close to that of free drug, demonstrating that the drug was effectively delivered by the particles and that the particles could act as an intracellular drug depot. Following in vitro characterization, murine in vivo studies demonstrated the ability of the paclitaxel-loaded responsive nanoparticles to delay recurrence of lung cancer and to prevent establishment of breast cancer in the mammary fat pads with higher efficacy than paclitaxel alone. In addition, the ability of nanoparticles to

  4. New developments in breast cancer therapy: role of iron oxide nanoparticles

    Thoidingjam, Shivani; Bhan Tiku, Ashu

    2017-06-01

    Breast cancer is one of the leading causes of deaths in females worldwide. The high metastatic rate and drug resistance makes it one of the difficult cancers to treat. Early diagnosis and treatment are keys to better survival of breast cancer patients. Conventional treatment approaches like chemotherapy, radiotherapy and surgery suffer from major drawbacks. Novel approaches to improve cancer therapy with minimal damage to normal tissues and better quality of life for cancer patients need to be developed. Among various approaches used for treatment and diagnosis of breast cancer, use of nanoparticles (NPs) is coming up as a new and promising treatment regime. It can help overcome various limitations of conventional therapies like non-targeted effects, resistance to treatment, late diagnosis, etc. Among various nanoparticles studied for their biomedical applications, especially for breast cancer therapy, iron oxide nanoparticles (IONPs) are perhaps the most exciting due to their biocompatibility, biodegradability, size and properties like superparamagnetism. Besides, IONPs are also the only metal oxide nanoparticles approved for clinical use in magnetic resonance imaging (MRI) which is an added advantage for early detection. Therefore in this mini review, we are discussing the developments made in the use of IONPs for breast cancer therapy over the short span of the last five years i.e. 2010-2015. Since late diagnosis and therapy resistance are important drawbacks in breast cancer therapy, the potential of IONPs to overcome these limitations are also evaluated.

  5. Hyaluronic acid-modified zirconium phosphate nanoparticles for potential lung cancer therapy.

    Li, Ranwei; Liu, Tiecheng; Wang, Ke

    2017-02-01

    Novel tumor-targeting zirconium phosphate (ZP) nanoparticles modified with hyaluronic acid (HA) were developed (HA-ZP), with the aim of combining the drug-loading property of ZP and the tumor-targeting ability of HA to construct a tumor-targeting paclitaxel (PTX) delivery system for potential lung cancer therapy. The experimental results indicated that PTX loading into the HA-ZP nanoparticles was as high as 20.36%±4.37%, which is favorable for cancer therapy. PTX-loaded HA-ZP nanoparticles increased the accumulation of PTX in A549 lung cancer cells via HA-mediated endocytosis and exhibited superior anticancer activity in vitro. In vivo anticancer efficacy assay revealed that HA-ZP nanoparticles possessed preferable anticancer abilities, which exhibited minimized toxic side effects of PTX and strong tumor-suppression potential in clinical application.

  6. Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain.

    Gdowski, Andrew S; Ranjan, Amalendu; Sarker, Marjana R; Vishwanatha, Jamboor K

    2017-09-01

    The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

  7. Nanoparticle mediated ablation of breast cancer cells using a nanosecond pulsed electric field

    Burford, Christopher

    In the past, both nanomaterials and various heating modalities have been researched as means for treating cancers. However, many of the current methodologies have the flaws of inconsistent tumor ablation and significant destruction of healthy cells. Based on research performed using constant radiofrequency electric fields and metallic nanoparticles (where cell necrosis is induced by the heating of these nanoparticles) we have developed a modality that simlarly uses functionalized metallic nanoparticles, specific for the T47D breast cancer cell line, and nanosecond pulsed electric fields as the hyperthermic inducer. Using both iron oxide and gold nanoparticles the results of our pilot studies indicated that up to 90% of the cancer cells were ablated given the optimal treatment parameters. These quantities of ablated cells were achieved using a cumulative exposure time 6 orders of magnitude less than most in vitro radiofrequency electric field studies.

  8. The Role of Dextran Coatings on the Cytotoxicity Properties of Ceria Nanoparticles Toward Bone Cancer Cells

    Yazici, Hilal; Alpaslan, Ece; Webster, Thomas J.

    2015-04-01

    Cerium oxide nanoparticles have demonstrated great potential as antioxidant and radioprotective agents for nanomedicine applications especially for cancer therapy. The surface chemistry of nanoparticles is an important property that has a significant effect on their performance in biological applications including cancer diagnosis, cancer treatment, and bacterial infection. Recently, various nanosized cerium oxide particles with different types of polymer coatings have been developed to improve aqueous solubility and allow for surface functionalization for distinct applications. In this study, the role of ceria nanoparticles coated with dextran on the cytotoxicity properties of bone cancer cells was shown. Specifically, 0.1 M and 0.01 M dextran-coated, coated ceria nanoparticles was evaluated against osteosarcoma cells. A change in cell viability was observed when treating osteosarcoma cells with 0.1 M dextran-coated ceria nanoparticles in the 250 -1000 μg/mL concentration range. In contrast, minimal toxicity to bone cancer cells was observed for the 0.01 M dextran coating after 3 days compared with the 0.1 M dextran coating. These results indicated that surface dextran functionalization had a positive impact on the cytotoxicity of cerium oxide nanoparticles against osteosarcoma cells.

  9. Fe3O4@Au composite magnetic nanoparticles modified with cetuximab for targeted magneto-photothermal therapy of glioma cells.

    Lu, Qianling; Dai, Xinyu; Zhang, Peng; Tan, Xiao; Zhong, Yuejiao; Yao, Cheng; Song, Mei; Song, Guili; Zhang, Zhenghai; Peng, Gang; Guo, Zhirui; Ge, Yaoqi; Zhang, Kangzhen; Li, Yuntao

    2018-01-01

    Thermoresponsive nanoparticles have become an attractive candidate for designing combined multimodal therapy strategies because of the onset of hyperthermia and their advantages in synergistic cancer treatment. In this paper, novel cetuximab (C225)-encapsulated core-shell Fe 3 O 4 @Au magnetic nanoparticles (Fe 3 O 4 @Au-C225 composite-targeted MNPs) were created and applied as a therapeutic nanocarrier to conduct targeted magneto-photothermal therapy against glioma cells. The core-shell Fe 3 O 4 @Au magnetic nanoparticles (MNPs) were prepared, and then C225 was further absorbed to synthesize Fe 3 O 4 @Au-C225 composite-targeted MNPs. Their morphology, mean particle size, zeta potential, optical property, magnetic property and thermal dynamic profiles were characterized. After that, the glioma-destructive effect of magnetic fluid hyperthermia (MFH) combined with near-infrared (NIR) hyperthermia mediated by Fe 3 O 4 @Au-C225 composite-targeted MNPs was evaluated through in vitro and in vivo experiments. The inhibitory and apoptotic rates of Fe 3 O 4 @Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group were significantly higher than other groups in vitro and the marked upregulation of caspase-3, caspase-8, and caspase-9 expression indicated excellent antitumor effect by inducing intrinsic apoptosis. Furthermore, Fe 3 O 4 @Au-C225 composite-targeted MNPs-mediated combined hyperthermia (MFH+NIR) group exhibited significant tumor growth suppression compared with other groups in vivo. Our studies illustrated that Fe 3 O 4 @Au-C225 composite-targeted MNPs have great potential as a promising nanoplatform for human glioma therapy and could be of great value in medical use in the future.

  10. Hyaluronan degrading silica nanoparticles for skin cancer therapy

    Scodeller, P.; Catalano, P. N.; Salguero, N.; Duran, H.; Wolosiuk, A.; Soler-Illia, G. J. A. A.

    2013-09-01

    We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human melanoma bearing mice and compared with the non-immobilized enzyme, on the basis of equal enzymatic activity. Alcian Blue staining of A375 tumors indicated large overexpression of hyaluronan. At the end of the experiment, tumor volume reduction with SiNP-immobilized Hyal was significantly enhanced compared to non-immobilized Hyal. Field emission scanning electron microscopy (FE-SEM) images together with energy dispersive X-ray spectroscopy (EDS) spectra confirmed the presence of SiNP on the tumor. We mean a proof of concept: this extracellular matrix (ECM) degrading enzyme, immobilized on SiNP, is a more effective local adjuvant of cancer drugs than the non-immobilized enzyme. This could prove useful in future therapies using other or a combination of ECM degrading enzymes.We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human

  11. Magnetic nanoparticles for precision oncology: theranostic magnetic iron oxide nanoparticles for image-guided and targeted cancer therapy.

    Zhu, Lei; Zhou, Zhiyang; Mao, Hui; Yang, Lily

    2017-01-01

    Recent advances in the development of magnetic nanoparticles (MNPs) have shown promise in the development of new personalized therapeutic approaches for clinical management of cancer patients. The unique physicochemical properties of MNPs endow them with novel multifunctional capabilities for imaging, drug delivery and therapy, which are referred to as theranostics. To facilitate the translation of those theranostic MNPs into clinical applications, extensive efforts have been made on designing and improving biocompatibility, stability, safety, drug-loading ability, targeted delivery, imaging signal and thermal- or photodynamic response. In this review, we provide an overview of the physicochemical properties, toxicity and theranostic applications of MNPs with a focus on magnetic iron oxide nanoparticles.

  12. Docetaxel-loaded multilayer nanoparticles with nanodroplets for cancer therapy

    Oh KS

    2016-03-01

    Full Text Available Keun Sang Oh,1,* Kyungim Kim,1,* Byeong Deok Yoon,1 Hye Jin Lee,1 Dal Yong Park,1 Eun-yeong Kim,1 Kiho Lee,1 Jae Hong Seo,2 Soon Hong Yuk1,2 1College of Pharmacy, Korea University, Sejong, 2Biomedical Research Center, Korea University Guro Hospital, Guro-gu, Seoul, Republic of Korea *These authors contributed equally to this work Abstract: A mixture of docetaxel (DTX and Solutol® HS 15 (Solutol transiently formed nanodroplets when it was suspended in an aqueous medium. However, nanodroplets that comprised DTX and Solutol showed a rapid precipitation of DTX because of their unstable characteristics in the aqueous medium. The incorporation of nanodroplets that comprised DTX and Solutol through vesicle fusion and subsequent stabilization was designed to prepare multilayer nanoparticles (NPs with a DTX-loaded Solutol nanodroplet (as template NPs core for an efficient delivery of DTX as a chemotherapeutic drug. As a result, the DTX-loaded Solutol nanodroplets (~11.7 nm were observed to have an increased average diameter (from 11.7 nm to 156.1 nm and a good stability of the hydrated NPs without precipitation of DTX by vesicle fusion and multilayered structure, respectively. Also, a long circulation of the multilayer NPs was observed, and this was due to the presence of Pluronic F-68 on the surface of the multilayer NPs. This led to an improved antitumor efficacy based on the enhanced permeation and retention effect. Therefore, this study indicated that the multilayer NPs have a considerable potential as a drug delivery system with an enhanced therapeutic efficacy by blood circulation and with low side effects. Keywords: multilayer nanoparticles, Solutol, Pluronic F-68, docetaxel, cancer therapy

  13. Engineering of gadofluoroprobes: Broad-spectrum applications from cancer diagnosis to therapy

    Dutta, Ranu A., E-mail: ranu.dutta16@gmail.com [Nanotechnology Application Centre, University of Allahabad, Allahabad 211002 (India); NanoeRA medicare Private Limited, Uttar Pradesh (India); Sharma, Prashant K. [Nanotechnology Application Centre, University of Allahabad, Allahabad 211002 (India); Indian School of Mines, Dhanbad (India); Tiwari, Vandana [Department of Pathology, KGMU, Lucknow (India); Tiwari, Vivek; Patel, Anant B. [Centre for Cellular and Molecular Biology, Hyderabad (India); Pandey, Ravindra [Department of Physics, Michigan Technological University, Michigan 49931-1295 (United States); Pandey, Avinash C. [Nanotechnology Application Centre, University of Allahabad, Allahabad 211002 (India); NanoeRA medicare Private Limited, Uttar Pradesh (India); Bundelkhand University, Jhansi (India)

    2014-01-13

    The engineering of the Gadolinium based nanostructures have been demonstrated in this paper. Nanostructures of α-Gd{sub 2}S{sub 3} exhibit a unique transition between ferromagnetic state and paramagnetic state of the system. It was demonstrated that their properties could be tuned for a wide range of applications ranging from hyperthermia to Magnetic Resonance Imaging, owing to their magnetic moments and large relaxivities. Metallic Gd nanoparticles obtained by reduction method were employed for cancer imaging in mice. The Gd nanoparticles were coated with Curcumin and their biomedical implications in the field of simultaneous diagnosis and therapy of cancer and related diseases has been discussed.

  14. Engineering of gadofluoroprobes: Broad-spectrum applications from cancer diagnosis to therapy

    Dutta, Ranu A.; Sharma, Prashant K.; Tiwari, Vandana; Tiwari, Vivek; Patel, Anant B.; Pandey, Ravindra; Pandey, Avinash C.

    2014-01-01

    The engineering of the Gadolinium based nanostructures have been demonstrated in this paper. Nanostructures of α-Gd 2 S 3 exhibit a unique transition between ferromagnetic state and paramagnetic state of the system. It was demonstrated that their properties could be tuned for a wide range of applications ranging from hyperthermia to Magnetic Resonance Imaging, owing to their magnetic moments and large relaxivities. Metallic Gd nanoparticles obtained by reduction method were employed for cancer imaging in mice. The Gd nanoparticles were coated with Curcumin and their biomedical implications in the field of simultaneous diagnosis and therapy of cancer and related diseases has been discussed

  15. Paradoxical Roles of Nanoparticles in Cancer Therapeutics and Carcinogenesis

    Despeaux, Emily

    Nanoparticles (NPs) are becoming increasingly common in consumer goods and are under investigation for a variety of industrial and biomedical applications. However, challenges in determining NP toxicity may prevent them from reaching their full potential. NPs cannot be treated as single class for toxicity evaluations. Even among particles made from the same material, particle-specific physical properties, including size, shape, surface charge, agglomeration state, and surface modifications have a strong effect on the toxicity. Even so, the obstacles to conclusively and reproducibly evaluating toxicity span all NP classes. NP literature is riddled with confusing and often contradictory reports regarding the biocompatibility of both engineered NPs, designed with biocompatibility as a priority, and NPs from occupational or environmental exposures. Incomplete NP characterization and sample inhomogeneity represent major confounding factors in disparate results from seemingly comparable study setups. Additionally, NPs can interfere with many conventional toxicity screening methods. Inappropriate doses, exposure routes, and toxicity endpoints further diminish the utility of many published studies. Given the burgeoning interest in NP-based therapeutic agents, consistent, reliable standards are needed to ensure the biocompatibility of new formulations. To those ends, the synthesis, characterization, and in vitro toxicity of a multi-functional NP therapeutic were investigated (Chapter 2). Specifically, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with amphiphilic polymer and functionalized with antisense oligonucleotides targeting survivin, an anti-apoptotic protein that is highly overexpressed in cancer. SPION physical properties, including particle size and composition, were characterized at each step of synthesis. Our results showed that the SPION platform is biocompatible and capable of delivering functional antisense oligonucleotides to regulate

  16. Hyperthermia stimulates HIV-1 replication.

    Ferdinand Roesch

    Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

  17. Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors

    Almeida, Patrick V.; Shahbazi, Mohammad-Ali; Mäkilä, Ermei; Kaasalainen, Martti; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A.

    2014-08-01

    Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi-HA+ relies on the capability of the conjugated HA+ to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA+-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery.Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA+) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA+ nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of Un

  18. Feasibility of MR imaging in evaluating breast cancer lymphangiogenesis using Polyethylene glycol-GoldMag nanoparticles

    Yang, H.; Zou, L.G.; Zhang, S.; Gong, M.F.; Zhang, D.; Qi, Y.Y.; Zhou, S.W.; Diao, X.W.

    2013-01-01

    Aim: To investigate the feasibility of evaluating tumour lymphangiogenesis using magnetic resonance imaging (MRI) in vivo. Materials and methods: Water-soluble polyethylene glycol (PEG)-GoldMag nanoparticles were obtained by combining GoldMag with PEG. The PEG-GoldMag nanoparticles were bound to anti-podoplanin antibody (PodAb) to construct PEG-GoldMag-pod molecular probes targeting lymphatic endothelial cells (LECs). The characteristics of the PEG-GoldMag-pod nanoparticles were tested. Using these nanoparticles, tumour lymphangiogenesis was evaluated using MRI in vitro and in vivo. Results: The average size of PEG-GoldMag nanoparticles was about 66.8 nm, and the nanoparticles were stably dispersed in the liquid phase for at least 15 days. After incubation for 24 h at different iron concentrations ranging from 5–45 μg/ml, the LECs were labelled with PEG-GoldMag-pod nanoparticles, in particular the breast cancer LECs. Dose-dependence was observed in the labelling efficiencies and MRI images of the labelled cells. In vitro, the labelling efficiencies and MRI images showed that the nanoparticles could detect podoplanin expression in LECs. In induced rat models of breast cancer, PEG-GoldMag-pod nanoparticles combined with lymphatic vessels were significantly detectable at MRI 60 min after nanoparticle administration, the signal intensity was negatively correlated with the lymphatic vessel density of breast cancer (r = −0.864, P = 0.000). Conclusions: The present study proves the feasibility of evaluating tumour lymphangiogenesis with MRI in vivo

  19. 3-Dimensional quantitative detection of nanoparticle content in biological tissue samples after local cancer treatment

    Rahn, Helene, E-mail: helene.rahn@gmail.com [Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Technische Universitaet Dresden, Dresden 01069 (Germany); Alexiou, Christoph [ENT-Department, Section for Experimental Oncology and Nanomedicine (Else Kröner-Fresenius-Stiftungsprofessur), University Hospital Erlangen, Waldstraße 1, Erlangen 91054 (Germany); Trahms, Lutz [Physikalisch-Technische Bundesanstalt, Abbestraße 2-12, Berlin 10587 (Germany); Odenbach, Stefan [Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Technische Universitaet Dresden, Dresden 01069 (Germany)

    2014-06-01

    X-ray computed tomography is nowadays used for a wide range of applications in medicine, science and technology. X-ray microcomputed tomography (XµCT) follows the same principles used for conventional medical CT scanners, but improves the spatial resolution to a few micrometers. We present an example of an application of X-ray microtomography, a study of 3-dimensional biodistribution, as along with the quantification of nanoparticle content in tumoral tissue after minimally invasive cancer therapy. One of these minimal invasive cancer treatments is magnetic drug targeting, where the magnetic nanoparticles are used as controllable drug carriers. The quantification is based on a calibration of the XµCT-equipment. The developed calibration procedure of the X-ray-µCT-equipment is based on a phantom system which allows the discrimination between the various gray values of the data set. These phantoms consist of a biological tissue substitute and magnetic nanoparticles. The phantoms have been studied with XµCT and have been examined magnetically. The obtained gray values and nanoparticle concentration lead to a calibration curve. This curve can be applied to tomographic data sets. Accordingly, this calibration enables a voxel-wise assignment of gray values in the digital tomographic data set to nanoparticle content. Thus, the calibration procedure enables a 3-dimensional study of nanoparticle distribution as well as concentration. - Highlights: • Local cancer treatments are promising in reducing negative side effects occurring during conventional chemotherapy. • The nanoparticles play an important role in delivering drugs to the designated area during local cancer treatments as magnetic drug targeting. • We study the nanoparticles distribution in tumor tissue after magnetic drug targeting with X-ray computed tomography. • We achieved a 3-dimensional quantification of the nanoparticles content in tumor tissue out of digital tomographic data.

  20. Self-assembled gemcitabine-gadolinium nanoparticles for magnetic resonance imaging and cancer therapy.

    Li, Lele; Tong, Rong; Li, Mengyuan; Kohane, Daniel S

    2016-03-01

    Nanoparticles with combined diagnostic and therapeutic functions are promising tools for cancer diagnosis and treatment. Here, we demonstrate a theranostic nanoparticle that integrates an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile supramolecular self-assembly synthesis, where the anti-cancer drug gemcitabine-5'-monophosphate (a phosphorylated active metabolite of the anti-cancer drug gemcitabine) was used to coordinate with Gd(III) to self-assemble into theranostic nanoparticles. The formulation exhibits a strong T1 contrast signal for magnetic resonance imaging of tumors in vivo, with enhanced retention time. Furthermore, the nanoparticles did not require other inert nanocarriers or excipients and thus had an exceptionally high drug loading (55 wt%), resulting in the inhibition of MDA-MB-231 tumor growth in mice. Recent advances in nanoparticle-based drug delivery systems have spurred the development of "theranostic" multifunctional nanoparticles, which combine therapeutic and diagnostic functionalities in a single formulation. Developing simple and efficient synthetic strategies for the construction of nanotheranostics with high drug loading remains a challenge. Here, we demonstrate a theranostic nanoparticle that integrates high loadings of an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile synthesis. The nanoparticles were better T1 contrast agents than currently used Gd-DTPA and had prolonged retention in tumor. Moreover they exhibited enhanced in vivo antitumor activity compared to free drug in a breast cancer xenograft mouse model. The strategy provides a scalable way to fabricate nanoparticles that enables enhancement of both therapeutic and diagnostic capabilities. Published by Elsevier Ltd.

  1. Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer

    Cohen Sarit

    2012-08-01

    Full Text Available Abstract Background The use of near-infrared (NIR fluorescence imaging techniques has gained great interest for early detection of cancer because water and other intrinsic biomolecules display negligible absorption or autofluorescence in this region. Novel fluorescent nanoparticles with potential to improve neoplasm detection sensitivity may prove to be a valuable tool in early detection of colon tumors. Methods The present study describes the synthesis and use of NIR fluorescent albumin nanoparticles as a diagnostic tool for detection of colon cancer. These fluorescent nanoparticles were prepared by a precipitation process of human serum albumin (HSA in aqueous solution in the presence of a carboxylic acid derivative of the NIR dye IR-783 (CANIR. Tumor-targeting ligands such as peanut agglutinin (PNA, anti-carcinoembryonic antigen antibodies (anti-CEA and tumor associated glycoprotein-72 monoclonal antibodies (anti-TAG-72 were covalently conjugated to the albumin nanoparticles via the surface carboxylate groups by using the carbodiimide activation method. Results and discussion Leakage of the encapsulated dye into PBS containing 4% HSA or human bowel juice was not detected. This study also demonstrates that the encapsulation of the NIR fluorescent dye within the HSA nanoparticles reduces the photobleaching of the dye significantly. Specific colon tumor detection in a mouse model was demonstrated for PNA, anti-CEA and anti-TAG-72 conjugated NIR fluorescent HSA nanoparticles. These bioactive NIR fluorescent albumin nanoparticles also detected invisible tumors that were revealed as pathological only subsequent to histological analysis. Conclusions These results may suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent nanoparticles over regular colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs, such as paclitaxel and doxorubicin, within these biodegradable NIR fluorescent HSA

  2. Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer.

    Cohen, Sarit; Margel, Shlomo

    2012-08-14

    The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer because water and other intrinsic biomolecules display negligible absorption or autofluorescence in this region. Novel fluorescent nanoparticles with potential to improve neoplasm detection sensitivity may prove to be a valuable tool in early detection of colon tumors. The present study describes the synthesis and use of NIR fluorescent albumin nanoparticles as a diagnostic tool for detection of colon cancer. These fluorescent nanoparticles were prepared by a precipitation process of human serum albumin (HSA) in aqueous solution in the presence of a carboxylic acid derivative of the NIR dye IR-783 (CANIR). Tumor-targeting ligands such as peanut agglutinin (PNA), anti-carcinoembryonic antigen antibodies (anti-CEA) and tumor associated glycoprotein-72 monoclonal antibodies (anti-TAG-72) were covalently conjugated to the albumin nanoparticles via the surface carboxylate groups by using the carbodiimide activation method. Leakage of the encapsulated dye into PBS containing 4% HSA or human bowel juice was not detected. This study also demonstrates that the encapsulation of the NIR fluorescent dye within the HSA nanoparticles reduces the photobleaching of the dye significantly. Specific colon tumor detection in a mouse model was demonstrated for PNA, anti-CEA and anti-TAG-72 conjugated NIR fluorescent HSA nanoparticles. These bioactive NIR fluorescent albumin nanoparticles also detected invisible tumors that were revealed as pathological only subsequent to histological analysis. These results may suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent nanoparticles over regular colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs, such as paclitaxel and doxorubicin, within these biodegradable NIR fluorescent HSA nanoparticles, in order to use them for both detection as well as therapy of colon

  3. Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging

    Glasgow, Micah D. K.; Chougule, Mahavir B.

    2016-01-01

    Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug’s therapeutic effectiveness while reducing adverse side effects associated with high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expressing on tumor tissues compared to normal cells, an “active” molecular marker targeted approach would be beneficial for cancer therapy. These actively targeted nanoparticles would increase drug concentration at the tumor site, improving efficacy while further reducing chemo-resistance. The multidisciplinary approach may help to improve the overall efficacy in cancer therapy. This review article summarizes recent developments of targeted multifunctional nanoparticles in the delivery of various drugs for a combinational chemotherapy approach to cancer treatment and imaging. PMID:26554150

  4. Use of the Concept of Equivalent Biologically Effective Dose (BED) to Quantify the Contribution of Hyperthermia to Local Tumor Control in Radiohyperthermia Cervical Cancer Trials, and Comparison With Radiochemotherapy Results

    Plataniotis, George A.; Dale, Roger G.

    2009-01-01

    Purpose: To express the magnitude of contribution of hyperthermia to local tumor control in radiohyperthermia (RT/HT) cervical cancer trials, in terms of the radiation-equivalent biologically effective dose (BED) and to explore the potential of the combined modalities in the treatment of this neoplasm. Materials and Methods: Local control rates of both arms of each study (RT vs. RT+HT) reported from randomized controlled trials (RCT) on concurrent RT/HT for cervical cancer were reviewed. By comparing the two tumor control probabilities (TCPs) from each study, we calculated the HT-related log cell-kill and then expressed it in terms of the number of 2 Gy fraction equivalents, for a range of tumor volumes and radiosensitivities. We have compared the contribution of each modality and made some exploratory calculations on the TCPs that might be expected from a combined trimodality treatment (RT+CT+HT). Results: The HT-equivalent number of 2-Gy fractions ranges from 0.6 to 4.8 depending on radiosensitivity. Opportunities for clinically detectable improvement by the addition of HT are only available in tumors with an alpha value in the approximate range of 0.22-0.28 Gy -1 . A combined treatment (RT+CT+HT) is not expected to improve prognosis in radioresistant tumors. Conclusion: The most significant improvements in TCP, which may result from the combination of RT/CT/HT for locally advanced cervical carcinomas, are likely to be limited only to those patients with tumors of relatively low-intermediate radiosensitivity.

  5. A Novel Docetaxel-Loaded Poly (ɛ-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

    Mei, Lin; Zhang, Yangqing; Zheng, Yi; Tian, Ge; Song, Cunxian; Yang, Dongye; Chen, Hongli; Sun, Hongfan; Tian, Yan; Liu, Kexin; Li, Zhen; Huang, Laiqiang

    2009-12-01

    Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (ɛ-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively. PCL/Pluronic F68 nanoparticles were found to be of spherical shape with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PCL/Pluronic F68 nanoparticles in docetaxel-resistance human breast cancer cell line, MCF-7 TAX30, when compared with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxotere® in the MCF-7 TAX30 cell culture, but the differences were not significant ( p > 0.05). However, the PCL/Pluronic F68 nanoparticles achieved significantly higher level of cytotoxicity than both of PCL nanoparticles and Taxotere® ( p < 0.05), indicating docetaxel-loaded PCL/Pluronic F68 nanoparticles could overcome multidrug resistance in human breast cancer cells and therefore have considerable potential for treatment of breast cancer.

  6. Rational Design of Multifunctional Gold Nanoparticles via Host-Guest Interaction for Cancer-Targeted Therapy.

    Chen, Wei-Hai; Lei, Qi; Luo, Guo-Feng; Jia, Hui-Zhen; Hong, Sheng; Liu, Yu-Xin; Cheng, Yin-Jia; Zhang, Xian-Zheng

    2015-08-12

    A versatile gold nanoparticle-based multifunctional nanocomposite AuNP@CD-AD-DOX/RGD was constructed flexibly via host-guest interaction for targeted cancer chemotherapy. The pH-sensitive anticancer prodrug AD-Hyd-DOX and the cancer-targeted peptide AD-PEG8-GRGDS were modified on the surface of AuNP@CD simultaneously, which endowed the resultant nanocomposite with the capability to selectively eliminate cancer cells. In vitro studies indicated that the AuNP@CD-AD-DOX/RGD nanocomposite was preferentially uptaken by cancer cells via receptor-mediated endocytosis. Subsequently, anticancer drug DOX was released rapidly upon the intracellular trigger of the acid microenvirenment of endo/lysosomes, inducing apoptosis in cancer cells. As the ideal drug nanocarrier, the multifunctional gold nanoparticles with the active targeting and controllable intracellular release ability hold the great potential in cancer therapy.

  7. Magnetic hyperthermia of laponite based ferrofluid

    Diamantopoulos, G., E-mail: gior15@ims.demokritos.gr [Institute of Materials Science, National Centre for Scientific Research ‘Demokritos’, 153 10 Aghia Paraskevi, Athens (Greece); Basina, G.; Tzitzios, V.; Karakosta, E.; Fardis, M. [Institute of Materials Science, National Centre for Scientific Research ‘Demokritos’, 153 10 Aghia Paraskevi, Athens (Greece); Jaglicic, Z. [University of Ljubljana, Faculty of Civil Engineering and Geodesy and Institute of Mathematics, Physics and Mechanics, Jadranska 19, 1000 Ljubljana (Slovenia); Lazaridis, N. [Aristotle University of Thessaloniki, Chemistry Department, 54124 Thessaloniki (Greece); Papavassiliou, G. [Institute of Materials Science, National Centre for Scientific Research ‘Demokritos’, 153 10 Aghia Paraskevi, Athens (Greece)

    2013-06-15

    Magnetic Hyperthermia experiments have been performed on different concentrations of magnetic iron oxide nanoparticles immobilized on nano-clay disks. The specific absorption rate (SAR) was measured in AC field amplitudes H{sub 0} from 7 to 30 kA/m. At low field amplitudes, SAR followed the usual H{sub 0}{sup 2} law whereas for higher field amplitudes a linear dependence was found for the higher concentrations. Measurements at three different field amplitudes were also performed for a wide range of iron oxide concentrations in order to determine the effect of the Brownian relaxation time to SAR. A field dependent maximum was observed and for fields up to 20 kA/m the power dissipation losses were well explained according to theoretical predictions. - Highlights: ► Influence of the AC field to the specific absorption rates (SAR). ► Transition point from the expected square dependence to a linear law between SAR and AC field amplitude. ► A field dependent maximum of the SAR values versus iron oxide concentration is observed. ► Experimental validation of the existing theoretical work.

  8. Magnetic nanoparticles for theragnostics

    Shubayev, Veronica I.; Pisanic, Thomas R.; Jin, Sungho

    2009-01-01

    Engineered magnetic nanoparticles (MNPs) represent a cutting-edge tool in medicine because they can be simultaneously functionalized and guided by a magnetic field. Use of MNPs has advanced magnetic resonance imaging (MRI), guided drug and gene delivery, magnetic hyperthermia cancer therapy, tissue engineering, cell tracking and bioseparation. Integrative therapeutic and diagnostic (i.e., theragnostic) applications have emerged with MNP use, such as MRI-guided cell replacement therapy or MRI-based imaging of cancer-specific gene delivery. However, mounting evidence suggests that certain properties of nanoparticles (e.g., enhanced reactive area, ability to cross cell and tissue barriers, resistance to biodegradation) amplify their cytotoxic potential relative to molecular or bulk counterparts. Oxidative stress, a 3-tier paradigm of nanotoxicity, manifests in activation of reactive oxygen species (ROS) (tier I), followed by a pro-inflammatory response (tier II) and DNA damage leading to cellular apoptosis and mutagenesis (tier III). In vivo administered MNPs are quickly challenged by macrophages of the reticuloendothelial system (RES), resulting in not only neutralization of potential MNP toxicity but also reduced circulation time necessary for MNP efficacy. We discuss the role of MNP size, composition and surface chemistry in their intracellular uptake, biodistribution, macrophage recognition and cytotoxicity, and review current studies on MNP toxicity, caveats of nanotoxicity assessments and engineering strategies to optimize MNPs for biomedical use. PMID:19389434

  9. Silica nanoparticles doped with anthraquinone for lung cancer phototherapy.

    de Souza Oliveira, Ronaldo Custodio; Corrêa, Rodrigo José; Teixeira, Raquel Simas Pereira; Queiroz, Daniela Dias; da Silva Souza, Rodrigo; Garden, Simon John; de Lucas, Nanci Camara; Pereira, Marcos Dias; Bello Forero, Josué Sebastián; Romani, Eric Cardona; Ribeiro, Emerson Schwingel

    2016-12-01

    In the present study, SiO 2 nanoparticles functionalized with 3-(2-aminoethylamino)propyl group (SiNP-AAP) were used, for the first time, to covalently bond rose bengal (SiNP-AAP-RB) or 9,10-anthraquinone-2-carboxylic acid (SiNP-AAP-OCAq). The functionalized SiNP were characterized by: Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM); elemental analysis (CHN) for determination of the dye concentration; FTIR and UV-vis diffuse reflectance (DR-UV-vis) and a surface area study (BET). The functionalized SiNPs were applied in photodynamic therapy (PDT) against lung cancer cell lines. The evaluated cytotoxicity revealed 20-30% cell survival after 15min of PDT for both materials but the OCAq concentration was half of the RB nanomaterial. The phototoxicity was mainly related to oxidative stress generated in the cellular environment by singlet oxygen and by hydrogen abstraction as confirmed by the laser flash photolysis technique. The unprecedented results indicate that SiNP-AAP-OCAq is a possible system for promoting cell apoptosis by both type I and type II mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Glypican-3 Targeting of Liver Cancer Cells Using Multifunctional Nanoparticles

    James O. Park

    2011-01-01

    Full Text Available Imaging is essential in accurately detecting, staging, and treating primary liver cancer (hepatocellular carcinoma [HCC], one of the most prevalent and lethal malignancies. We developed a novel multifunctional nanoparticle (NP specifically targeting glypican-3 (GPC3, a proteoglycan implicated in promotion of cell growth that is overexpressed in most HCCs. Quantitative real-time polymerase chain reaction was performed to confirm the differential GPC3 expression in two human HCC cells, Hep G2 (high and HLF (negligible. These cells were treated with biotin-conjugated GPC3 monoclonal antibody (αGPC3 and subsequently targeted using superparamagnetic iron oxide NPs conjugated to streptavidin and Alexa Fluor 647. Flow cytometry demonstrated that only GPC3-expressing Hep G2 cells were specifically targeted using this αGPC3-NP conjugate (fourfold mean fluorescence over nontargeted NP, and magnetic resonance imaging (MRI experiments showed similar findings (threefold R2 relaxivity. Confocal fluorescence microscopy localized the αGPC3 NPs only to the cell surface of GPC3-expressing Hep G2 cells. Further characterization of this construct demonstrated a negatively charged, monodisperse, 50 nm NP, ideally suited for tumor targeting. This GPC3-specific NP system, with dual-modality imaging capability, may enhance pretreatment MRI, enable refined intraoperative HCC visualization by near-infrared fluorescence, and be potentially used as a carrier for delivery of tumor-targeted therapies, improving patient outcomes.

  11. IGF1 Receptor Targeted Theranostic Nanoparticles for Targeted and Image-Guided Therapy of Pancreatic Cancer.

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Wang, Liya; Wang, Y Andrew; Chen, Hongyu; Kooby, David; Yu, Qian; Lipowska, Malgorzata; Staley, Charles A; Mao, Hui; Yang, Lily

    2015-08-25

    Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.

  12. Targeting thyroid cancer with acid-triggered release of doxorubicin from silicon dioxide nanoparticles

    Li SJ

    2017-08-01

    Full Text Available Shijie Li,1 Daqi Zhang,1 Shihou Sheng,2 Hui Sun1 1Department of Thyroid Surgery, 2Department of Gastrointestinal Colorectal and Anal Surgery, China–Japan Union Hospital of Jilin University, Chang Chun, People’s Republic of China Abstract: Currently, therapy for thyroid cancer mainly involves surgery and radioiodine therapy. However, chemotherapy can be used in advanced and aggressive thyroid cancer that cannot be treated by other options. Nevertheless, a major obstacle to the successful treatment of thyroid cancer is the delivery of drugs to the thyroid gland. Here, we present an example of the construction of silicon dioxide nanoparticles with thyroid–stimulating-hormone receptor-targeting ligand that can specifically target the thyroid cancer. Doxorubicin nanoparticles can be triggered by acid to release the drug payload for cancer therapy. These nanoparticles shrink the tumor size in vivo with less toxic side effects. This research paves the way toward effective chemotherapy for thyroid cancer. Keywords: thyroid cancer, silicon dioxide nanoparticle, doxorubicin, acid-triggered release

  13. Magnetic nanoparticle biodistribution following intratumoral administration

    Giustini, A J; Hoopes, P J [Dartmouth Medical School and the Thayer School of Engineering, 8000 Cummings Hall, Dartmouth College, Hanover, NH 03755 (United States); Ivkov, R, E-mail: andrew.j.giustini@dartmouth.edu [Triton BioSystems, Inc. , Chelmsford, MA 01824 (United States)

    2011-08-26

    Recently, heat generated by iron oxide nanoparticles (IONPs) stimulated by an alternating magnetic field (AMF) has shown promise in the treatment of cancer. To determine the mechanism of nanoparticle-induced cytotoxicity, the physical association of the cancer cells and the nanoparticles must be determined. We have used transmission electron microscopy (TEM) to define the time dependent cellular uptake of intratumorally administered dextran-coated, core-shell configuration IONP having a mean hydrodynamic diameter of 100-130 nm in a murine breast adenocarcinoma cell line (MTG-B) in vivo. Tumors averaging volumes of 115 mm{sup 3} were injected with iron oxide nanoparticles. The tumors were then excised and fixed for TEM at time 0.1-120 h post-IONP injection. Intracellular uptake of IONPs was 5.0, 48.8 and 91.1% uptake at one, 2 and 4 h post-injection of IONPs, respectively. This information is essential for the effective use of IONP hyperthermia in cancer treatment.

  14. Multimodal doxorubicin loaded magnetic nanoparticles for VEGF targeted theranostics of breast cancer.

    Semkina, Alevtina S; Abakumov, Maxim A; Skorikov, Alexander S; Abakumova, Tatiana O; Melnikov, Pavel A; Grinenko, Nadejda F; Cherepanov, Sergey A; Vishnevskiy, Daniil A; Naumenko, Victor A; Ionova, Klavdiya P; Majouga, Alexander G; Chekhonin, Vladimir P

    2018-05-03

    In presented paper we have developed new system for cancer theranostics based on vascular endothelial growth factor (VEGF) targeted magnetic nanoparticles. Conjugation of anti-VEGF antibodies with bovine serum albumin coated PEGylated magnetic nanoparticles allows for improved binding with murine breast adenocarcinoma 4T1 cell line and facilitates doxorubicin delivery to tumor cells. It was shown that intravenous injection of doxorubicin loaded VEGF targeted nanoparticles increases median survival rate of mice bearing 4T1 tumors up to 50%. On the other hand magnetic resonance imaging (MRI) of 4T1 tumors 24 h after intravenous injection showed accumulation of nanoparticles in tumors, thus allowing simultaneous cancer therapy and diagnostics. Copyright © 2018. Published by Elsevier Inc.

  15. On the improvement of regional hyperthermia treatment

    Kroeze, Hugo

    2002-01-01

    Hyperthermia is an adjuvant treatment modality to radiotherapy and/or chemotherapy, with the aim of increasing the tumour killing effect of the treatment. It involves the elevation of the tumour temperature to ~ 42oC. Radiofrequent heating is a practical method for hyperthermia: a number of

  16. An in-vitro studies on green synthesis of gold nanoparticles against pathogens and cancer cells

    V. Ramesh

    2015-11-01

    Full Text Available Nanotechnology is a most promising field for generating new applications in medicine. It is imperative to integrate nanoscience and medicine. The present investigation is highly warranted to through more light upon the gold nanoparticles reduced from gold salt through the active principle of medicinal plant. The special emphasis of investigation is the active principle along with gold nanoparticles against for cancer cells. The 70 - 90 nm sized particles were synthesized by using Diospyros ferrea and this confirmed by SEM. These gold nanoparticles showed a characteristic absorption peak at 540 nm in UV spectra. The possibility of protein as a stabilizing material in gold nanoparticles is revealed by FTIR analysis. Remarkably, as a result of wide screening on the application of newly synthesized gold nanoparticles their anticancer potential has been discovered using MTT assay. The antimicrobial activity of AuNPs showed effective against bacteria than the fungal strains.

  17. Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy.

    Purushotham, S; Ramanujan, R V

    2010-02-01

    The synthesis, characterization and property evaluation of drug-loaded polymer-coated magnetic nanoparticles (MNPs) relevant to multimodal cancer therapy has been studied. The hyperthermia and controlled drug release characteristics of these particles was examined. Magnetite (Fe(3)O(4))-poly-n-(isopropylacrylamide) (PNIPAM) composite MNPs were synthesized in a core-shell morphology by dispersion polymerization of n-(isopropylacrylamide) chains in the presence of a magnetite ferrofluid. These core-shell composite particles, with a core diameter of approximately 13nm, were loaded with the anti-cancer drug doxorubicin (dox), and the resulting composite nanoparticles (CNPs) exhibit thermoresponsive properties. The magnetic properties of the composite particles are close to those of the uncoated magnetic particles. In an alternating magnetic field (AMF), composite particles loaded with 4.15 wt.% dox exhibit excellent heating properties as well as simultaneous drug release. Drug release testing confirmed that release was much higher above the lower critical solution temperature (LCST) of the CNP, with a release of up to 78.1% of bound dox in 29h. Controlled drug release testing of the particles reveals that the thermoresponsive property can act as an on/off switch by blocking drug release below the LCST. Our work suggests that these dox-loaded polymer-coated MNPs show excellent in vitro hyperthermia and drug release behavior, with the ability to release drugs in the presence of AMF, and the potential to act as agents for combined targeting, hyperthermia and controlled drug release treatment of cancer.

  18. Orthogonal Clickable Iron Oxide Nanoparticle Platform for Targeting, Imaging, and On-Demand Release.

    Guldris, Noelia; Gallo, Juan; García-Hevia, Lorena; Rivas, José; Bañobre-López, Manuel; Salonen, Laura M

    2018-04-12

    A versatile iron oxide nanoparticle platform is reported that can be orthogonally functionalized to obtain highly derivatized nanomaterials required for a wide variety of applications, such as drug delivery, targeted therapy, or imaging. Facile functionalization of the nanoparticles with two ligands containing isocyanate moieties allows for high coverage of the surface with maleimide and alkyne groups. As a proof-of-principle, the nanoparticles were subsequently functionalized with a fluorophore as a drug model and with biotin as a targeting ligand towards tumor cells through Diels-Alder and azide-alkyne cycloaddition reactions, respectively. The thermoreversibility of the Diels-Alder product was exploited to induce the on-demand release of the loaded molecules by magnetic hyperthermia. Additionally, the nanoparticles were shown to target cancer cells through in vitro experiments, as analyzed by magnetic resonance imaging. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Folate receptor targeted 17-allylamino-17-demethoxygeldanamycin (17-AAG) loaded polymeric nanoparticles for breast cancer.

    Saxena, Vipin; Naguib, Youssef; Hussain, M Delwar

    2012-06-01

    Low water solubility and hepatotoxicity limited the clinical use of 17-allylamino-17-demethoxy geldanamycin (17-AAG), an inhibitor of heat shock protein 90 (HSP90). Folate targeted polylactide-co-glycolide-polyethylene glycol-folic acid (PLGA-PEG-FA) nanoparticles containing 17-AAG were prepared and characterized. Cellular uptake and in vitro cytotoxicity of the prepared nanoparticles were determined in MCF-7 human breast cancer cells. The particle size of 17-AAG loaded folate targeted nanoparticles was 238.67±3.52 nm, drug loading was 8.25±2.49% and about 80% of drug was released from the nanoparticles over 10 days. Cellular uptake studies showed much higher intracellular uptake of folate targeted nanoparticle as compared to nontargeted nanoparticles. Cytotoxicity study showed 2 fold increase (PAAG loaded PLGA-PEG-FA nanoparticles might be developed as a targeted delivery system for breast and other cancer treatment. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. The Preclinical Evaluation of Fever-Range, Whole Body Hyperthermia as a Adjuvant to Chemotherapy and Cytokine Immunotherapy for the Treatment of Breast Cancer

    Pritchard, Michele

    2002-01-01

    .... Mechanisms behind the observed enhancement in anti-tumor response remain to be clearly identified although work using another mouse model for human colon cancer suggests that the down stream effector...

  1. Nanoparticles of Selaginella doederleinii leaf extract inhibit human lung cancer cells A549

    Syaefudin; Juniarti, A.; Rosiyana, L.; Setyani, A.; Khodijah, S.

    2016-01-01

    The aim of the present study is to evaluate cytotoxicity effect of nanoparticles of Selaginella doederleinii (S. doederleinii) leaves extract. S. doederleinii was extracted by maceration method using 70%(v/v) ethanol as solvent. Phytochemical content was analyzed qualitatively by using Harborne and Thin Layer Chromatography (TLC) methods. Nanoparticle extract was prepared by ionic gelation using chitosan as encapsulant agent. Anticancer activity was performed by using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results showed that S. doederleinii contains of flavonoids. Nanoparticle of S. doederleinii leaves extract greatly inhibited A549 cells growth (cancer cells), with IC50 of 3% or 1020 μg/ml. These nanoparticles extract also inhibited the growth of Chang cells (normal cells), with IC50 of 4% or 1442 μg/ml. The effective concentration of nanoparticles extract which inhibits cancer cells without harming the normal cells is 0.5% or 167 μg/ml. Further studies are needed to obtain the concentration of nanoparticles extract which can selectively suppress cancer cells.

  2. Aptamer-modified nanoparticles and their use in cancer diagnostics and treatment.

    Reinemann, Christine; Strehlitz, Beate

    2014-01-06

    Aptamers are single-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) oligonucleotides, which are able to bind their target with high selectivity and affinity. Owing to their multiple talents, aptamers combined with nanoparticles are nanosystems well qualified for the development of new biomedical devices for analytical, imaging, drug delivery and many other medical applications. Because of their target affinity, aptamers can direct the transport of aptamer-nanoparticle conjugates. The binding of the aptamers to the target "anchors" the nanoparticle-aptamer conjugates at their site of action. In this way, nanoparticle-based bioimaging and smart drug delivery are enabled, especially by use of systematically developed aptamers for cancer-associated biomarkers. This review article gives a brief overview of recent relevant research into aptamers and trends in their use in cancer diagnostics and therapy. A concise description of aptamers, their development and functionalities relating to nanoparticle modification is given. The main part of the article is dedicated to current developments of aptamer-modified nanoparticles and their use in cancer diagnostics and treatment.

  3. Multilayered Magnetic Nanoparticles Fabricated by Nanoimprint Lithography for Magnetomechanical Treatment of Cancer

    Kwon, Byung Seok

    Fe3O4-magetite nanoparticles have received wide interest as prominent agents for various biomedical applications, ranging from target-specific cancer treatment, gene therapy, and Magnetic Particle Imaging (MPI). However, Fe3O4-magnetite nanoparticles, synthesized by chemical methods beyond a certain size, present challenges in controlling size distribution and shape. Similarly, Fe3O 4-magnetite nanoparticles fabricated by conventional top-down lithographic methods present difficulty of controlling defects and lead to agglomeration due to large size. In order to overcome the difficulties associated with the conventional chemical and top-down lithographic methods, it is critical to develop a fabrication method which produces homogeneous nanoparticles in large quantities with the control of size, defects, and structure. Furthermore, the concept of cell death induced by mechanical perturbation has received wide attention as a way to maximize the cancer cell death with minimal side effects. Previous study has proposed the use of permalloy disk-shaped vortex state microparticles, in order to create cancer cell death by mechanical force. However, insufficient biocompatibility, inadequate mechanical force created by vortex switching, and inability to control the particle size have been critical issues to be further researched and proceeded for in vivo application. Hence, we studied physical and magnetic properties of Fe3O 4 as a material in thin film form and proceeded to develop Fe3 O4 based synthetic antiferromagnetic (SAF) thin films. Then, we combined these favorable physical/magnetic properties with nanoimprint lithography to fabricate homogeneously patterned synthetic antiferromagnetic (SAF) nanoparticles (wafer area >1 x 1 cm2) with the control of size, shape and structure. Then we demonstrated the release of these particles in an aqueous environment. The fabrication process combines a tetrafluoroethylene (ETFE) "working stamp", a bi-layer resist lift-off, defect

  4. Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer-90Y conjugates in treatment of prostate tumors

    Buckway, Brandon; Frazier, Nick; Gormley, Adam J.; Ray, Abhijit; Ghandehari, Hamidreza

    2014-01-01

    Introduction: The treatment of prostate cancer using a radiotherapeutic 90 Y labeled N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer can be enhanced with localized tumor hyperthermia. An 111 In labeled HPMA copolymer system for single photon emission computerized tomography (SPECT) was developed to observe the biodistribution changes associated with hyperthermia. Efficacy studies were conducted in prostate tumor bearing mice using the 90 Y HPMA copolymer with hyperthermia. Methods: HPMA copolymers containing 1, 4, 7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were synthesized by reversible addition-fragmentation transfer (RAFT) copolymerization and subsequently labeled with either 111 In for imaging or 90 Y for efficacy studies. Radiolabel stability was characterized in vitro with mouse serum. Imaging and efficacy studies were conducted in DU145 prostate tumor bearing mice. Imaging was performed using single photon emission computerized tomography (SPECT). Localized mild tumor hyperthermia was achieved by plasmonic photothermal therapy using gold nanorods. Results: HPMA copolymer-DOTA conjugates demonstrated efficient labeling and stability for both radionuclides. Imaging analysis showed a marked increase of radiolabeled copolymer within the hyperthermia treated prostate tumors, with no significant accumulation in non-targeted tissues. The greatest reduction in tumor growth was observed in the hyperthermia treated tumors with 90 Y HPMA copolymer conjugates. Histological analysis confirmed treatment efficacy and safety. Conclusion: HPMA copolymer-DOTA conjugates radiolabeled with both the imaging and treatment radioisotopes, when combined with hyperthermia can serve as an image guided approach for efficacious treatment of prostate tumors

  5. Advances in nanotheranostics II cancer theranostic nanomedicine

    2016-01-01

    This book surveys recent advances in theranostics based on magnetic nanoparticles, ultrasound contrast agents, silica nanoparticles and polymeric micelles. It presents magnetic nanoparticles, which offer a robust tool for contrast enhanced MRI imaging, magnetic targeting, controlled drug delivery, molecular imaging guided gene therapy, magnetic hyperthermia, and controlling cell fate. Multifunctional ultrasound contrast agents have great potential in ultrasound molecular imaging, multimodal imaging, drug/gene delivery, and integrated diagnostics and therapeutics. Due to their diversity and multifunctionality, polymeric micelles and silica-based nanocomposites are highly capable of enhancing the efficacy of multimodal imaging and synergistic cancer therapy. This comprehensive book summarizes the main advances in multifunctional nanoprobes for targeted imaging and therapy of gastric cancer, and explores the clinical translational prospects and challenges. Although more research is needed to overcome the substan...

  6. Dual-Color Fluorescence Imaging of Magnetic Nanoparticles in Live Cancer Cells Using Conjugated Polymer Probes

    Sun, Minjie; Sun, Bin; Liu, Yun; Shen, Qun-Dong; Jiang, Shaojun

    2016-01-01

    Rapid growth in biological applications of nanomaterials brings about pressing needs for exploring nanomaterial-cell interactions. Cationic blue-emissive and anionic green-emissive conjugated polymers are applied as dual-color fluorescence probes to the surface of negatively charged magnetic nanoparticles through sequentially electrostatic adsorption. These conjugated polymers have large extinction coefficients and high fluorescence quantum yield (82% for PFN and 62% for ThPFS). Thereby, one can visualize trace amount (2.7 μg/mL) of fluorescence-labeled nanoparticles within cancer cells by confocal laser scanning microscopy. Fluorescence labeling by the conjugated polymers is also validated for quantitative determination of the internalized nanoparticles in each individual cell by flow cytometry analysis. Extensive overlap of blue and green fluorescence signals in the cytoplasm indicates that both conjugated polymer probes tightly bind to the surface of the nanoparticles during cellular internalization. The highly charged and fluorescence-labeled nanoparticles non-specifically bind to the cell membranes, followed by cellular uptake through endocytosis. The nanoparticles form aggregates inside endosomes, which yields a punctuated staining pattern. Cellular internalization of the nanoparticles is dependent on the dosage and time. Uptake efficiency can be enhanced three-fold by application of an external magnetic field. The nanoparticles are low cytotoxicity and suitable for simultaneously noninvasive fluorescence and magnetic resonance imaging application. PMID:26931282

  7. Principles and concept 1993 of the systemic cancer multistep therapy (sCMT). Extreme whole-body hyperthermia using the infrared-A technique IRATHERM 2000 - selective thermosensitisation by hyperglycemia - circulatory back-up by adapted hyperoxemia

    Ardenne, M. von [Von Ardenne Inst. of Applied Medical Research, Dresden (Germany)

    1994-10-01

    The so-called Cancer Multistep Therapy was conceived by the author in 1965. It is a combined modality treatment with 3 process steps: Whole-body hyperthermia, hyperglycemia and hyperoxemia. The original therapy concept was further developed into a systemic Cancer Multistep Therapy (sCMT) of high efficiency and selectivity. An outline follows of this therapy and the actual state of the sCMT concept as per 1993 (new in timing, dosage, technique). Knowledge of the synergetic-additive efficiency of various groups of cytostatics reacting to the effects of the main treatment process steps (WBH+HG+HO) led in 1974 to an extension of the sCMT concept by including chemotherapy. In addition, a radiotherapeutical treatment was included in this concept as cancer cells clearly show a higher sensibility to radiation while under the influence of sCMT. Following the sCMT treatment, the patient remains under observation on an intensive in-patient basis for 24 hours before he or she is discharged for out-patient post-treatment care. The systemic tolerance of sCMT with minimal side-effects has been proven with several 100 patients and results have been published as part of the phase-I study. A first evaluation of the efficacy of sCMT was documented in the same study. (orig.) [Deutsch] 1965 wurde vom Autor die sogenannte Krebs-Mehrschritt-Therapie konzipiert. Es handelt sich hierbei um eine kombinierte Behandlung, bestehend aus Ganzkoerperhyperthermie, Hyperglykaemie und Hyperoxaemie. Die Weiterentwicklung der aelteren Therapiekonzepte bis hin zu einer systemischen Krebs-Mehrschritt-Therapie (sKMT) hoher Effizienz und Selektivitaet wird skizziert und der heutige Stand des sKMT-Konzeptes 1993 dargestellt. Es wurde ein strahlentherapeutischer Schritt in das Konzept aufgenommen, da unter der Wirkung der Hauptschritte eine deutlich erhoehte Strahlensensibilitaet der Krebszellen gegeben ist. Somit besteht das sKMT-Konzept 1993 aus den Hauptschritten Hyperthermie, Hyperglykaemie

  8. Phase II-trial of radiation therapy with 45 Gy, 5-fluorouracil (5-FU) and mitomycin C (MMC) in patients with anal cancer - a rationale to add regional hyperthermia?

    Graf, R.; Wust, P.; Gellermann, J.; Mohr, B.; Goegler, H.; Riess, H.; Felix, R.

    1996-01-01

    Purpose: To evaluate the effect of standard regimen of chemoradiation for anal cancer with a radiation dose of 45 Gy on survival, local control and toxicity with respect to the discussion about intensification of therapy. Assessment of prognostic factors and designing improved treatment strategies for certain risk groups. Materials and Methods: From 1987 to 1995 46 patients with localized anal cancer were eligible. Thirty-five women and 11 men with a median age of 54 years were treated according to the protocoll. Thirty-two (70%) patients had histologically a squamous cell carcinoma, 12 (26%) a cloacogenic carcinoma. Thirty-one patients (68%) had T1, T2 tumors, 15 patients (33%) had locally advanced primary tumors (T3, T4), 9 patients (20%) had N1-3 disease. Radiotherapy consisted of 30 Gy to the primary tumor and pelvic lymph nodes, followed by one week treatment break and boost to the primary tumor to a total dose of 45 Gy with a single dose of 2 Gy, mean duration of radiotherapy 44 days. 5-FU was given on days 1-5 and 29-33 as continuous infusion (800 mg/m 2 /day), MMC (10 mg/m 2 ) was given intravenously as bolus on day 1 and 29. Patients were followed for survival and local control. Toxicity was assessed using Common Toxicity Criteria and the LENT score (late effects normal tissues). The mean follow-up time was 34,4 months. Results: The cancer specific actuarial 5-year survival rate was 69%: 79% in T1, T2 and 41% in T3, T4 tumors (p = 0,03). The 5-year actuarial local control rate was 74%: 89% in T1, T2 tumors, 42% ind T3, T4 tumors (p 5 cm): p 4 cm): p = 0,04, depth of infiltration: p < 0,00, response: p < 0,00. No local control was achievable for tumors greater than 6 cm, whereas all local failures occurred when there was extrasphincteric infiltration. Conclusions: Colostomy-free survival was unsatisfactory. Depth of infiltration (extrasphincteric involvement) as well as tumor size (≥ 5 cm) has been shown as negative prognostic factor for local control

  9. NON-INVASIVE RADIOFREQUENCY ABLATION OF CANCER TARGETED BY GOLD NANOPARTICLES

    Cardinal, Jon; Klune, John Robert; Chory, Eamon; Jeyabalan, Geetha; Kanzius, John S.; Nalesnik, Michael; Geller, David A.

    2008-01-01

    Introduction Current radiofrequency ablation (RFA) techniques require invasive needle placement and are limited by accuracy of targeting. The purpose of this study was to test a novel non-invasive radiowave machine that uses RF energy to thermally destroy tissue. Gold nanoparticles were designed and produced to facilitate tissue heating by the radiowaves. Methods A solid state radiowave machine consisting of a power generator and transmitting/receiving couplers which transmit radiowaves at 13.56 MHz was used. Gold nanoparticles were produced by citrate reduction and exposed to the RF field either in solutions testing or after incubation with HepG2 cells. A rat hepatoma model using JM-1 cells and Fisher rats was employed using direct injection of nanoparticles into the tumor to focus the radiowaves for select heating. Temperatures were measured using a fiber-optic thermometer for real-time data. Results Solutions containing gold nanoparticles heated in a time- and power-dependent manner. HepG2 liver cancer cells cultured in the presence of gold nanoparticles achieved adequate heating to cause cell death upon exposure to the RF field with no cytotoxicity attributable to the gold nanoparticles themselves. In vivo rat exposures at 35W using gold nanoparticles for tissue injection resulted in significant temperature increases and thermal injury at subcutaneous injection sites as compared to vehicle (water) injected controls. Discussion These data show that non-invasive radiowave thermal ablation of cancer cells is feasible when facilitated by gold nanoparticles. Future studies will focus on tumor selective targeting of nanoparticles for in vivo tumor destruction. PMID:18656617

  10. Green synthesis of anisotropic gold nanoparticles for photothermal therapy of cancer.

    Fazal, Sajid; Jayasree, Aswathy; Sasidharan, Sisini; Koyakutty, Manzoor; Nair, Shantikumar V; Menon, Deepthy

    2014-06-11

    Nanoparticles of varying composition, size, shape, and architecture have been explored for use as photothermal agents in the field of cancer nanomedicine. Among them, gold nanoparticles provide a simple platform for thermal ablation owing to its biocompatibility in vivo. However, the synthesis of such gold nanoparticles exhibiting suitable properties for photothermal activity involves cumbersome routes using toxic chemicals as capping agents, which can cause concerns in vivo. Herein, gold nanoparticles, synthesized using green chemistry routes possessing near-infrared (NIR) absorbance facilitating photothermal therapy, would be a viable alternative. In this study, anisotropic gold nanoparticles were synthesized using an aqueous route with cocoa extract which served both as a reducing and stabilizing agent. The as-prepared gold nanoparticles were subjected to density gradient centrifugation to maximize its NIR absorption in the wavelength range of 800-1000 nm. The particles also showed good biocompatibility when tested in vitro using A431, MDA-MB231, L929, and NIH-3T3 cell lines up to concentrations of 200 μg/mL. Cell death induced in epidermoid carcinoma A431 cells upon irradiation with a femtosecond laser at 800 nm at a low power density of 6 W/cm(2) proved the suitability of green synthesized NIR absorbing anisotropic gold nanoparticles for photothermal ablation of cancer cells. These gold nanoparticles also showed good X-ray contrast when tested using computed tomography (CT), proving their feasibility for use as a contrast agent as well. This is the first report on green synthesized anisotropic and cytocompatible gold nanoparticles without any capping agents and their suitability for photothermal therapy.

  11. Optimal design of implants for magnetically mediated hyperthermia: A wireless power transfer approach

    Lang, Hans-Dieter; Sarris, Costas D.

    2017-09-01

    In magnetically mediated hyperthermia (MMH), an externally applied alternating magnetic field interacts with a mediator (such as a magnetic nanoparticle or an implant) inside the body to heat up the tissue in its proximity. Producing heat via induced currents in this manner is strikingly similar to wireless power transfer (WPT) for implants, where power is transferred from a transmitter outside of the body to an implanted receiver, in most cases via magnetic fields as well. Leveraging this analogy, a systematic method to design MMH implants for optimal heating efficiency is introduced, akin to the design of WPT systems for optimal power transfer efficiency. This paper provides analytical formulas for the achievable heating efficiency bounds as well as the optimal operating frequency and the implant material. Multiphysics simulations validate the approach and further demonstrate that optimization with respect to maximum heating efficiency is accompanied by minimizing heat delivery to healthy tissue. This is a property that is highly desirable when considering MMH as a key component or complementary method of cancer treatment and other applications.

  12. Hyperthermia with rotating magnetic nanowires inducing heat into tumor by fluid friction

    Egolf, Peter W.; Pawlowski, Anne-Gabrielle; Tsague, Paulin; Marco, Bastien de; Bovy, William; Tucev, Sinisa [Institute of Thermal Sciences and Engineering, University of Applied Sciences of Western Switzerland, CH 1401 Yverdon-les-Bains (Switzerland); Shamsudhin, Naveen, E-mail: snaveen@ethz.ch; Pané, Salvador; Pokki, Juho; Ansari, M. H. D.; Nelson, Bradley J. [Multi-Scale Robotics Lab, Institute of Robotics and Intelligent Systems, ETH Zurich, CH 8092 Zurich (Switzerland); Vuarnoz, Didier [Ecole Polytechnique Fédérale de Lausanne (EPFL), EPFL Fribourg, CH 1701 Fribourg (Switzerland)

    2016-08-14

    A magnetic hyperthermia cancer treatment strategy that does not operate by means of conventional heating mechanisms is presented. The proposed approach consists of injecting a gel with homogeneously distributed magnetic nanowires into a tumor. Upon the application of a low-frequency rotating or circularly polarized magnetic field, nanowires spin around their center of viscous drag due to torque generated by shape anisotropy. As a result of external rotational forcing and fluid friction in the nanoparticle's boundary layer, heating occurs. The nanowire dynamics is theoretically and experimentally investigated, and different feasibility proofs of the principle by physical modeling, which adhere to medical guidelines, are presented. The magnetic nanorotors exhibit rotations and oscillations with quite a steady center of gravity, which proves an immobile behavior and guarantees a time-independent homogeneity of the spatial particle distribution in the tumor. Furthermore, a fluid dynamic and thermodynamic heating model is briefly introduced. This model is a generalization of Penne's model that for this method reveals theoretic heating rates that are sufficiently high, and fits well into medical limits defined by present standards.

  13. Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

    Yun-Jung Choi

    2016-12-01

    Full Text Available The cancer stem cell (CSC hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs. In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH and CD133 by fluorescence-activated cell sorting (FACS. The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH, reactive oxygen species (ROS, and mitochondrial membrane potential (mt-MP. The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells. These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

  14. Nanoparticle delivered vascular disrupting agents (VDAs): use of TNF-alpha conjugated gold nanoparticles for multimodal cancer therapy.

    Shenoi, Mithun M; Iltis, Isabelle; Choi, Jeunghwan; Koonce, Nathan A; Metzger, Gregory J; Griffin, Robert J; Bischof, John C

    2013-05-06

    Surgery, radiation and chemotherapy remain the mainstay of current cancer therapy. However, treatment failure persists due to the inability to achieve complete local control of the tumor and curtail metastatic spread. Vascular disrupting agents (VDAs) are a class of promising systemic agents that are known to synergistically enhance radiation, chemotherapy or thermal treatments of solid tumors. Unfortunately, there is still an unmet need for VDAs with more favorable safety profiles and fewer side effects. Recent work has demonstrated that conjugating VDAs to other molecules (polyethylene glycol, CNGRCG peptide) or nanoparticles (liposomes, gold) can reduce toxicity of one prominent VDA (tumor necrosis factor alpha, TNF-α). In this report, we show the potential of a gold conjugated TNF-α nanoparticle (NP-TNF) to improve multimodal cancer therapies with VDAs. In a dorsal skin fold and hindlimb murine xenograft model of prostate cancer, we found that NP-TNF disrupts endothelial barrier function and induces a significant increase in vascular permeability within the first 1-2 h followed by a dramatic 80% drop in perfusion 2-6 h after systemic administration. We also demonstrate that the tumor response to the nanoparticle can be verified using dynamic contrast-enhanced magnetic resonance imaging (MRI), a technique in clinical use. Additionally, multimodal treatment with thermal therapies at the perfusion nadir in the sub- and supraphysiological temperature regimes increases tumor volumetric destruction by over 60% and leads to significant tumor growth delays compared to thermal therapy alone. Lastly, NP-TNF was found to enhance thermal therapy in the absence of neutrophil recruitment, suggesting that immune/inflammatory regulation is not central to its power as part of a multimodal approach. Our data demonstrate the potential of nanoparticle-conjugated VDAs to significantly improve cancer therapy by preconditioning tumor vasculature to a secondary insult in a targeted

  15. Large specific absorption rates in the magnetic hyperthermia properties of metallic iron nanocubes

    Mehdaoui, B.; Meffre, A.; Lacroix, L.-M. [Universite de Toulouse, INSA, UPS, LPCNO (Laboratoire de Physique et Chimie des Nano-Objets), 135 avenue de Rangueil, F-31077 Toulouse (France); CNRS, UMR 5215, LPCNO, F-31077 Toulouse (France); Carrey, J., E-mail: julian.carrey@insa-toulouse.f [Universite de Toulouse, INSA, UPS, LPCNO (Laboratoire de Physique et Chimie des Nano-Objets), 135 avenue de Rangueil, F-31077 Toulouse (France); CNRS, UMR 5215, LPCNO, F-31077 Toulouse (France); Lachaize, S. [Universite de Toulouse, INSA, UPS, LPCNO (Laboratoire de Physique et Chimie des Nano-Objets), 135 avenue de Rangueil, F-31077 Toulouse (France); CNRS, UMR 5215, LPCNO, F-31077 Toulouse (France); Gougeon, M. [Institut CARNOT-CIRIMAT-UMR 5085, Batiment 2R1, 118 route de Narbonne, F-31062 Toulouse (France); Respaud, M. [Universite de Toulouse, INSA, UPS, LPCNO (Laboratoire de Physique et Chimie des Nano-Objets), 135 avenue de Rangueil, F-31077 Toulouse (France); CNRS, UMR 5215, LPCNO, F-31077 Toulouse (France); Chaudret, B. [Laboratoire de Chimie de Coordination-CNRS, 205 rte de Narbonne, 31077 Toulouse cedex 4 (France)

    2010-10-15

    We report on the magnetic hyperthermia properties of chemically synthesized ferromagnetic 11 and 16 nm Fe(0) nanoparticles of cubic shape displaying the saturation magnetization of bulk iron. The specific absorption rate measured on 16 nm nanocubes is 1690{+-}160 W/g at 300 kHz and 66 mT. This corresponds to specific losses-per-cycle of 5.6 mJ/g, largely exceeding the ones reported in other systems. A way to quantify the degree of optimization of any system with respect to hyperthermia applications is proposed. Applied here, this method shows that our nanoparticles are not fully optimized, probably due to the strong influence of magnetic interactions on their magnetic response. Once protected from oxidation and further optimized, such nano-objects could constitute efficient magnetic cores for biomedical applications requiring very large heating power.

  16. CD44-engineered mesoporous silica nanoparticles for overcoming multidrug resistance in breast cancer

    Wang, Xin; Liu, Ying; Wang, Shouju; Shi, Donghong; Zhou, Xianguang; Wang, Chunyan; Wu, Jiang; Zeng, Zhiyong; Li, Yanjun; Sun, Jing; Wang, Jiandong; Zhang, Longjiang; Teng, Zhaogang; Lu, Guangming

    2015-01-01

    Graphical abstract: - Highlights: • CD44-engineered mesoporous silica nanoparticles are synthesized. • The mechanism of CD44-engineered mesoporous silica nanoparticles is revealed. • This new delivery system increased the drug accumulation in vitro and in vivo. • This new delivery system offers an effective approach to treat multidrug resistance. - Abstract: Multidrug resistance is a major impediment for the successful chemotherapy in breast cancer. CD44 is over-expressed in multidrug resistant human breast cancer cells. CD44 monoclonal antibody exhibits anticancer potential by inhibiting proliferation and regulating P-glycoprotein-mediated drug efflux activity in multidrug resistant cells. Thereby, CD44 monoclonal antibody in combination with chemotherapeutic drug might be result in enhancing chemosensitivity and overcoming multidrug resistance. The purpose of this study is to investigate the effects of the CD44 monoclonal antibody functionalized mesoporous silica nanoparticles containing doxorubicin on human breast resistant cancer MCF-7 cells. The data showed that CD44-modified mesoporous silica nanoparticles increased cytotoxicity and enhanced the downregulation of P-glycoprotein in comparison to CD44 antibody. Moreover, CD44-engineered mesoporous silica nanoparticles provided active target, which promoted more cellular uptake of DOX in the resistant cells and more retention of DOX in tumor tissues than unengineered counterpart. Animal studies of the resistant breast cancer xenografts demonstrated that CD44-engineered drug delivery system remarkably induced apoptosis and inhibited the tumor growth. Our results indicated that the CD44-engineered mesoporous silica nanoparticle-based drug delivery system offers an effective approach to overcome multidrug resistance in human breast cancer

  17. Synthesis of highly stable folic acid conjugated magnetite nanoparticles for targeting cancer cells

    Mohapatra, S; Mallick, S K; Maiti, T K; Ghosh, S K; Pramanik, P

    2007-01-01

    A new approach towards the design of folic acid conjugated magnetic nanoparticles for enhancing their site specific intracellular uptake against a folate receptor overexpressing cancer cells is reported. Magnetite nanoparticles were prepared by coprecipitation from an Fe 3+ and Fe 2+ solution followed by surface modification with 2-carboxyethyl phosphonic acid to form carboxyl group terminated nanoparticles. Then folic acid and fluorescein isothiocyanate (FITC) were conjugated with carboxylic acid functionalized magnetite nanoparticles using 2,2'-(ethylenedioxy)-bis-ethylamine. These folate-conjugated nanoparticles were characterized in terms of their size by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Surface functional groups and surface composition were analyzed by Fourier transform infrared (FTIR) spectroscopy and x-ray photoelectron spectroscopy (XPS), respectively. Vibration sample magnetometry (VSM) measurements showed the superparamagnetic nature of the particles at room temperature. Folate-conjugated magnetic nanoparticles are noncytotoxic and receptor mediated internalization by HeLa and B16 melanoma F0 cancer cells was confirmed by flow cytometry and confocal microscopy

  18. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com [National Institute of Pharmaceutical Education and Research (NIPER), Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology (India)

    2015-01-15

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose.

  19. Nanoparticle-based photodynamic therapy on non-melanoma skin cancer

    Fanjul-Vélez, F.; Arce-Diego, J. L.

    2018-02-01

    There are several advantages of Photodynamic Therapy (PDT) for nonmelanoma skin cancer treatment compared to conventional treatment techniques such as surgery, radiotherapy or chemotherapy. Among these advantages its noninvasive nature, the use of non ionizing radiation and its high selectivity can be mentioned. Despite all these advantages, the therapeutic efficiency of the current clinical protocol is not complete in all the patients and depends on the type of pathology. An adequate dosimetry is needed in order to personalize the protocol. There are strategies that try to overcome the current PDT shortcomings, such as the improvement of the photosensitizer accumulation in the target tissue, optical radiation distribution optimization or photochemical reactions maximization. These strategies can be further complemented by the use of nanostructures with conventional PDT. Customized dosimetry for nanoparticle-based PDT requires models in order to adjust parameters of different nature to get an optimal tumor removal. In this work, a predictive model of nanoparticle-based PDT is proposed and analyzed. Dosimetry in nanoparticle-based PDT is going to be influenced by photosensitizer-nanoparticle distribution in the malignant tissue, its influence in the optical radiation distribution and the subsequent photochemical reactions. Nanoparticles are considered as photosensitizer carriers on several types of non-melanoma skin cancer. Shielding effects are taken into account. The results allow to compare the estimated treatment outcome with and without nanoparticles.

  20. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan

    2015-01-01

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose

  1. Synthesis of bombesin-functionalized iron oxide nanoparticles and their specific uptake in prostate cancer cells

    Martin, Amanda L.; Hickey, Jennifer L.; Ablack, Amber L.; Lewis, John D.; Luyt, Leonard G.; Gillies, Elizabeth R.

    2010-01-01

    The imaging of molecular markers associated with disease offers the possibility for earlier detection and improved treatment monitoring. Receptors for gastrin-releasing peptide are overexpressed on prostate cancer cells offering a promising imaging target, and analogs of bombesin, an amphibian tetradecapeptide have been previously demonstrated to target these receptors. Therefore, the pan-bombesin analog [β-Ala11, Phe13, Nle14]bombesin-(7-14) was conjugated through a linker to dye-functionalized superparamagnetic iron oxide nanoparticles for the development of a new potential magnetic resonance imaging probe. The peptide was conjugated via click chemistry, demonstrating a complementary alternative methodology to conventional peptide-nanoparticle conjugation strategies. The peptide-functionalized nanoparticles were then demonstrated to be selectively taken up by PC-3 prostate cancer cells relative to unfunctionalized nanoparticles and this uptake was inhibited by the presence of free peptide, confirming the specificity of the interaction. This study suggests that these nanoparticles have the potential to serve as magnetic resonance imaging probes for the detection of prostate cancer.

  2. Nanoparticles and cancer therapy: A concise review with emphasis on dendrimers

    Dhruba J Bharali

    2009-01-01

    Full Text Available Dhruba J Bharali, Marianne Khalil, Mujgan Gurbuz, Tessa M Simone, Shaker A MousaPharmaceutical Research Institute at Albany College of Pharmacy, Rensselaer, NY, USAAbstract: The emergence of nanotechnology has had a profound effect on many areas of healthcare and scientific research. Having grown exponentially, the focus of nanotechnology has been on engineering diversified novel applications that even go beyond therapeutic activity; nanotechnology also offers the ability to detect diseases, such as cancer, much earlier than ever imaginable. Often, patients diagnosed with breast, lung, colon, prostate, and ovarian cancer have hidden or overt metastatic colonies. With the advent of diagnostic nanotechnology, these numbers are expected to greatly diminish. This review provides a brief description of nanoparticle (liposome, quantum dot, and dendrimer-mediated cancer therapy in the last decade with an emphasis on the development and use of dendrimers in cancer therapeutics.Keywords: nanoparticles, dendrimer, quantum dots, liposome

  3. PLGA-Chitosan nanoparticle-mediated gene delivery for oral cancer treatment: A brief review

    Bakar, L. M.; Abdullah, M. Z.; Doolaanea, A. A.; Ichwan, S. J. A.

    2017-08-01

    Cancer becomes a serious issue on society with increasing of their growth and proliferation, either in well economic developed countries or not. Recent years, oral cancer is one of the most threatening diseases impairing the quality of life of the patient. Scientists have emphasised on application of gene therapy for oral cancer by using nanoparticle as transportation vectors as a new alternative platform in order to overcome the limitations of conventional approaches. In modern medicine, nanotechnologies’ application, such as nanoparticles-mediated gene delivery, is one of promising tool for therapeutic devices. The objective of this article is to present a brief review summarizes on the current progress of nanotechnology-based gene delivery treatment system targeted for oral cancer.

  4. Magnetic nanowires and hyperthermia: How geometry and material affect heat production efficiency

    Contreras, Maria F.

    2015-05-01

    Magnetic hyperthermia, which refers to the production of heat by magnetic nanostructures under an alternating magnetic field (AMF), has been previously investigated with superparamagnetic nanobeads as a cancer therapy method. Magnetic nanowires (NWs) used in hyperthermia can be very promising, as it has been shown that they have a larger magnetic moment per unit of volume compared to the nanobeads. Moreover, Fe NWs proved to have a higher heating efficiency compared to Fe nanobeads, when exposed to an AMF at the same concentration [1].

  5. Synthesis of curcumin-functionalized gold nanoparticles and cytotoxicity studies in human prostate cancer cell line

    Nambiar, Shruti; Osei, Ernest; Fleck, Andre; Darko, Johnson; Mutsaers, Anthony J.; Wettig, Shawn

    2018-03-01

    Gold nanoparticles synthesized using plant extracts with medicinal properties have gained traction in recent years, especially for their use in various biomedical applications. Colloidal stability of these nanoparticles in different environments is critical to retain the expected therapeutic/diagnostic efficacy and toxicological outcome. Any change in the colloidal stability leads to dramatic changes in the physico-chemical properties of the nanoparticles such as size and surface charge, which in turn may alter the biological activity of the particles. Such changes are imminent in physiologically-relevant environment wherein interactions with different biomolecules, such as serum proteins, may modify the overall properties of the nanoparticles. In this regard, we synthesized 15 nm sized gold nanoparticles using curcumin, a plant extract from turmeric root, to evaluate cytotoxicity, uptake, and localization in human prostate cancer cells using cell-culture medium supplemented with or without fetal bovine serum (FBS). The results indicate a dramatic difference in the cytotoxicity and uptake between cells treated with curcumin-functionalized gold nanoparticles (cur-AuNPs) in cell-culture medium with and without serum. The addition of FBS to the medium not only increased the stability of the nanoparticles but also enhanced the biocompatibility (i.e. minimal cytotoxicity for a wide range of cur-AuNP concentrations). We conclude that the presence of serum proteins significantly impact the therapeutic potential of cur-AuNPs.

  6. Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

    Kopelman, Raoul; Lee Koo, Yong-Eun; Philbert, Martin; Moffat, Bradford A.; Ramachandra Reddy, G.; McConville, Patrick; Hall, Daniel E.; Chenevert, Thomas L.; Bhojani, Mahaveer Swaroop; Buck, Sarah M.; Rehemtulla, Alnawaz; Ross, Brian D.

    2005-05-01

    A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment.

  7. Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

    Kopelman, Raoul; Lee Koo, Yong-Eun; Philbert, Martin; Moffat, Bradford A.; Ramachandra Reddy, G.; McConville, Patrick; Hall, Daniel E.; Chenevert, Thomas L.; Bhojani, Mahaveer Swaroop; Buck, Sarah M.; Rehemtulla, Alnawaz; Ross, Brian D.

    2005-01-01

    A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment

  8. Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

    Kopelman, Raoul [Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor MI 48109 (United States)]. E-mail: kopelman@umich.edu; Lee Koo, Yong-Eun [Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor MI 48109 (United States); Philbert, Martin [Environmental Health Sciences, niversity of Michigan (United States); Moffat, Bradford A. [Department of Radiology, The University of Michigan (United States); Ramachandra Reddy, G. [Molecular Therapeutics, Inc., Ann Arbor, MI 48104 (United States); McConville, Patrick [Molecular Therapeutics, Inc., Ann Arbor, MI 48104 (United States); Hall, Daniel E. [Department of Radiology, University of Michigan (United States); Chenevert, Thomas L. [Department of Radiology, University of Michigan (United States); Bhojani, Mahaveer Swaroop [Department of Radiation Oncology, University of Michigan (United States); Buck, Sarah M. [Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor MI 48109 (United States); Rehemtulla, Alnawaz [Department of Radiation Oncology, University of Michigan (United States); Ross, Brian D. [Department of Radiology, University of Michigan (United States)

    2005-05-15

    A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment.

  9. Magnetic Iron Oxide Nanoparticles for Multimodal Imaging and Therapy of Cancer

    In-Kyu Park

    2013-07-01

    Full Text Available Superparamagnetic iron oxide nanoparticles (SPION have emerged as an MRI contrast agent for tumor imaging due to their efficacy and safety. Their utility has been proven in clinical applications with a series of marketed SPION-based contrast agents. Extensive research has been performed to study various strategies that could improve SPION by tailoring the surface chemistry and by applying additional therapeutic functionality. Research into the dual-modal contrast uses of SPION has developed because these applications can save time and effort by reducing the number of imaging sessions. In addition to multimodal strategies, efforts have been made to develop multifunctional nanoparticles that carry both diagnostic and therapeutic cargos specifically for cancer. This review provides an overview of recent advances in multimodality imaging agents and focuses on iron oxide based nanoparticles and their theranostic applications for cancer. Furthermore, we discuss the physiochemical properties and compare different synthesis methods of SPION for the development of multimodal contrast agents.

  10. Gold Nanotheranostics: Photothermal Therapy and Imaging of Mucin 7 Conjugated Antibody Nanoparticles for Urothelial Cancer

    Chieh Hsiao Chen

    2015-01-01

    Full Text Available Objective. To kill urothelial cancer cells while preserving healthy cells, this study used photothermal therapy (PTT. PTT techniques target urothelial cancer cells using gold nanoparticles (GNPs and a green light laser. Materials and Methods. The GNPs were conjugated with anti-Mucin 7 antibodies, which acted as a probe for targeting tumor cells. Conjugated GNPs were exposed to a green light laser (532 nm with sufficient thermal energy to kill the transitional cell carcinomas (TCCs. Results. According to our results, nanoparticles conjugated with Mucin 7 antibodies damaged all types of cancer cells (MBT2, T24, 9202, and 8301 at relatively low energy levels (i.e., 500 laser shots at 10 W/cm2 in power, 1.6 Hz in frequency, and 300 ms in duration. Nonconjugated nanoparticles required 30 W/cm2 or more to achieve the same effect. Cell damage was directly related to irradiation time and applied laser energy. Conclusions. The minimally invasive PTT procedure combined with Mucin 7 targeted GNPs is able to kill cancer cells and preserve healthy cells. The success of this treatment technique can likely be attributed to the lower amount of energy required to kill targeted cancer cells compared with that required to kill nontargeted cancer cells. Our in vitro pilot study yielded promising results; however, additional animal studies are required to confirm these findings.

  11. Dual drug loaded chitosan nanoparticles-sugar--coated arsenal against pancreatic cancer.

    David, Karolyn Infanta; Jaidev, Leela Raghav; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

    2015-11-01

    Pancreatic cancer is an aggressive form of cancer with poor survival rates. The increased mortality due to pancreatic cancer arises due to many factors such as development of multidrug resistance, presence of cancer stem cells, development of a stromal barrier and a hypoxic environment due to hypo-perfusion. The present study aims to develop a nanocarrier for a combination of drugs that can address these multiple issues. Quercetin and 5-fluorouracil were loaded in chitosan nanoparticles, individually as well as in combination. The nanoparticles were characterized for morphology, size, zeta potential, percentage encapsulation of drugs as well as their release profiles in different media. The dual drug-loaded carrier exhibited good entrapment efficiency (quercetin 95% and 5-fluorouracil 75%) with chitosan: quercetin: 5-fluorouracil in the ratio 3:1:2. The release profiles suggest that 5-fluorouracil preferentially localized in the periphery while quercetin was located towards the core of chitosan nanoparticles. Both drugs exhibited considerable association with the chitosan matrix. The dual drug-loaded carrier system exhibited significant toxicity towards pancreatic cancer cells both in the 2D as well as in the 3D cultures. We believe that the results from these studies can open up interesting options in the treatment of pancreatic cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Magnetic fluid hyperthermia probed by both calorimetric and dynamic hysteresis measurements

    Guibert, Clément; Fresnais, Jérôme; Peyre, Véronique; Dupuis, Vincent, E-mail: vincent.dupuis@upmc.fr

    2017-01-01

    In this paper, we report an investigation of magnetic fluid hyperthermia (MFH) using combined calorimetric and newly implemented dynamic hysteresis measurements for two sets of well characterized size-sorted maghemite nanoparticles (with diameters of about 10 nm and 20 nm) dispersed in water and in glycerol. Our primary goal was to assess the influence of viscosity on the heating efficiency of magnetic nanoparticles described in terms of specific loss power (SLP or specific absorption rate, SAR) and dynamic hysteresis. In particular, we aimed to investigate how this SLP depends on the transition from Néelian to Brownian behavior of nanoparticles expected to occur between 10 nm and 20 nm (for maghemite) and dependent on the viscosity. While we observed a good agreement between calorimetric and dynamic hysteresis measurements, we found that the SLP measured for the different systems do not depend noticeably on the viscosity of solvent. Calculations performed according to Rosensweig's linear model [1] allow us to quantitatively reproduce our results at low field intensities, provided we use a value for the magnetic anisotropy constant much smaller than the one commonly used in the literature. This raises the question of the temperature dependance of the magnetic anisotropy constant and its relevance for a quantitative description of MFH. - Highlights: • Dynamic hysteresis measurements are a promising tool to study magnetic hyperthermia. • Dynamic hysteresis cycles can be reproduced using a simple model. • The effect of viscosity on hyperthermia of maghemite is weaker than expected.

  13. Cholecystokinin Receptor-Targeted Polyplex Nanoparticle Inhibits Growth and Metastasis of Pancreatic Cancer

    Julian Burks

    2018-01-01

    Conclusions: Our polyplex nanoparticle platform establishes both a strong foundation for the development of receptor-targeted therapeutics and a unique approach for the delivery of siRNA in vivo, thus warranting further exploration of this approach in other types of cancers.

  14. Nanoparticle-Based Drug Delivery for Therapy of Lung Cancer: Progress and Challenges

    Anish Babu

    2013-01-01

    Full Text Available The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ability to overcome biological barriers, effectively deliver hydrophobic therapies, and preferentially target disease sites. Currently, many formulations of nanocarriers are utilized including lipid-based, polymeric and branched polymeric, metal-based, magnetic, and mesoporous silica. Innovative strategies have been employed to exploit the multicomponent, three-dimensional constructs imparting multifunctional capabilities. Engineering such designs allows simultaneous drug delivery of chemotherapeutics and anticancer gene therapies to site-specific targets. In lung cancer, nanoparticle-based therapeutics is paving the way in the diagnosis, imaging, screening, and treatment of primary and metastatic tumors. However, translating such advances from the bench to the bedside has been severely hampered by challenges encountered in the areas of pharmacology, toxicology, immunology, large-scale manufacturing, and regulatory issues. This review summarizes current progress and challenges in nanoparticle-based drug delivery systems, citing recent examples targeted at lung cancer treatment.

  15. A new application of plant virus nanoparticles as drug delivery in breast cancer

    Esfandiari, Neda; Arzanani, Mohsen Karimi; Soleimani, Masoud

    2016-01-01

    used nanoparticles formed from the potato virus X to conjugate the Herceptin (Trastuzumab) monoclonal antibody as a new option in specific targeting of breast cancer. Bioconjugation was performed by EDC/sulfo-n-hydroxysuccinimide (sulfo-NHS) in a two-step protocol. Then, the efficiency of conjugation...

  16. Targeted Therapy Combined with Immune Modulation Using Gold Nanoparticles for Treating Metastatic Colorectal Cancer

    2017-09-01

    stimulate the body’s immune system to target and attack cancer cells. Another part of our research includes coating these gold nanoparticles with...change in animal care is the introduction of doxycycline through food chow in addition to drinking water. The dose of doxycycline from the drinking water

  17. Nanotechnology and cancer: improving real-time monitoring and staging of bladder cancer with multimodal mesoporous silica nanoparticles.

    Sweeney, Sean K; Luo, Yi; O'Donnell, Michael A; Assouline, Jose

    Despite being one of the most common cancers, bladder cancer is largely inefficiently and inaccurately staged and monitored. Current imaging methods detect cancer only when it has reached "visible" size and has significantly disrupted the structure of the organ. By that time, thousands of cells will have proliferated and perhaps metastasized. Repeated biopsies and scans are necessary to determine the effect of therapy on cancer growth. In this report, we describe a novel approach based on multimodal nanoparticle contrast agent technology and its application to a preclinical animal model of bladder cancer. The innovation relies on the engineering core of mesoporous silica with specific scanning contrast properties and surface modification that include fluorescence and magnetic resonance imaging (MRI) contrast. The overall dimensions of the nano-device are preset at 80-180 nm, depending on composition with a pore size of 2 nm. To facilitate and expedite discoveries, we combined a well-known model of bladder cancer and our novel technology. We exposed nanoparticles to MB49 murine bladder cancer cells in vitro and found that 70 % of the cells were labeled by nanoparticles as measured by flow cytometry. The in vivo mouse model for bladder cancer is particularly well suited for T1- and T2-weighted MRI. Under our experimental conditions, we demonstrate that the nanoparticles considerably improve tumor definition in terms of volumetric, intensity and structural characteristics. Important bladder tumor parameters can be ascertained, non-invasively, repetitively, and with great accuracy. Furthermore, since the particles are not biodegradable, repetitive injection is not required. This feature allows follow-up diagnostic evaluations during cancer treatment. Changes in MRI signals show that in situ uptake of free particles has predilection to tumor cells relative to normal bladder epithelium. The particle distribution within the tumors was corroborated by fluorescent

  18. Temperature responsive hydrogel magnetic nanocomposites for hyperthermia and metal extraction applications

    Reddy, N. Narayana, E-mail: nagireddynarayana@gmail.com [Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia@CRIB, Largo Barsanti e Matteucci 53, 80125 Napoli (Italy); Ravindra, S. [Department of Physics, College of Science, Engineering and Technology, University of South Africa, Johannesburg 1709 (South Africa); Reddy, N. Madhava [Department of Environmental Science, Gates Institute of Technology, NH-7, Gooty, Anantapuram, Andhra Pradesh (India); Rajinikanth, V. [Department of Physics, College of Science, Engineering and Technology, University of South Africa, Johannesburg 1709 (South Africa); Raju, K. Mohana [Synthetic Polymer Laboratory, Department of Polymer Science & Technology, S.K. University, Anantapuram, Andhra Pradesh (India); Vallabhapurapu, Vijaya Srinivasu [Department of Physics, College of Science, Engineering and Technology, University of South Africa, Johannesburg 1709 (South Africa)

    2015-11-15

    The present work deals with the development of temperature and magnetic responsive hydrogel networks based on poly (N-isopropylacrylamide)/acrylamido propane sulfonic acid. The hydrogel matrices are synthesized by polymerizing N-isopropylacrylamide (NIPAM) monomer in the presence of acrylamido propane sulphonicacid (AMPS) using a cross-linker (N,N-methylenebisacrylamide, MBA) and redox initiating system [ammonium persulphate (APS)/tetramethylethylenediamine (TMEDA)]. The magnetic nanoparticles are generated throughout the hydrogel networks using in situ method by incorporating iron ions and subsequent treatment with ammonia. A series of hydrogel-magnetic nanocomposites (HGMNC) are developed by varying AMPS composition. The synthesized hydrogel magnetic nanocomposites (HGMNC) are characterized by using Fourier Transform Infrared (FTIR) Spectroscopy, X-ray diffraction (XRD), Thermal Analyses and Electron Microscopy analysis (Scanning and Transmission Electron Microscope). The metal extraction capacities of the prepared hydrogel (HG) and hydrogel magnetic nanocomposites (HGMNC) were studied at different temperatures. The results suggest that HGMNCs have higher extraction capacity compared to HG and HG loaded iron ions. This data also reveals that the extraction of metals by hydrogel magnetic nanocomposites (HGMNCs) is higher at higher temperatures than room temperature. The prepared HGMNCs are also subjected to hyperthermia (cancer therapy) studies. - Highlights: • We have developed temperature responsive hydrogel magnetic nanocomposites. • Addition of AMPS monomer to this magnetic hydrogel enhances the temperature sensitivity to 40–43 °C. • Similarly the sulfonic groups present in the AMPS units enhances the swelling ratio of magnetic hydrogels. • AMPS acts as good stabilizing agent for nanoparticles in the magnetic nanogel.

  19. Temperature responsive hydrogel magnetic nanocomposites for hyperthermia and metal extraction applications

    Reddy, N. Narayana; Ravindra, S.; Reddy, N. Madhava; Rajinikanth, V.; Raju, K. Mohana; Vallabhapurapu, Vijaya Srinivasu

    2015-01-01

    The present work deals with the development of temperature and magnetic responsive hydrogel networks based on poly (N-isopropylacrylamide)/acrylamido propane sulfonic acid. The hydrogel matrices are synthesized by polymerizing N-isopropylacrylamide (NIPAM) monomer in the presence of acrylamido propane sulphonicacid (AMPS) using a cross-linker (N,N-methylenebisacrylamide, MBA) and redox initiating system [ammonium persulphate (APS)/tetramethylethylenediamine (TMEDA)]. The magnetic nanoparticles are generated throughout the hydrogel networks using in situ method by incorporating iron ions and subsequent treatment with ammonia. A series of hydrogel-magnetic nanocomposites (HGMNC) are developed by varying AMPS composition. The synthesized hydrogel magnetic nanocomposites (HGMNC) are characterized by using Fourier Transform Infrared (FTIR) Spectroscopy, X-ray diffraction (XRD), Thermal Analyses and Electron Microscopy analysis (Scanning and Transmission Electron Microscope). The metal extraction capacities of the prepared hydrogel (HG) and hydrogel magnetic nanocomposites (HGMNC) were studied at different temperatures. The results suggest that HGMNCs have higher extraction capacity compared to HG and HG loaded iron ions. This data also reveals that the extraction of metals by hydrogel magnetic nanocomposites (HGMNCs) is higher at higher temperatures than room temperature. The prepared HGMNCs are also subjected to hyperthermia (cancer therapy) studies. - Highlights: • We have developed temperature responsive hydrogel magnetic nanocomposites. • Addition of AMPS monomer to this magnetic hydrogel enhances the temperature sensitivity to 40–43 °C. • Similarly the sulfonic groups present in the AMPS units enhances the swelling ratio of magnetic hydrogels. • AMPS acts as good stabilizing agent for nanoparticles in the magnetic nanogel

  20. Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

    Hamon, Casey L.; Dorsey, Christopher L.; Özel, Tuğba; Barnes, Eugenia M.; Hudnall, Todd W.; Betancourt, Tania

    2016-01-01

    Nanoparticles are being readily investigated as carriers for the delivery of imaging and therapeutic agents for the detection, monitoring, and treatment of cancer and other diseases. In the present work, the preparation of biodegradable polymeric nanoparticles loaded with a near-infrared fluorescent aza-boron dipyrromethene (NIR-BODIPY) derivative, and their use as contrast agents for optical imaging in cancer are described. Nanoparticles were prepared by nanoprecipitation of amphiphilic block copolymers of poly(lactic acid) and poly(ethylene glycol). The size, morphology, dye loading, spectral properties, quantum yield, cytocompatibility, and in vitro NIR imaging potential of the nanoparticles in breast and ovarian cancer cells were evaluated. Spherical nanoparticles of 30–70 nm in diameter were loaded with 0.73 w/w% BODIPY derivative. At this loading, the dye presented a fluorescence quantum yield in the same order of magnitude as in solution. Nanoparticle suspensions at concentrations up to 580 μg/mL were cytocompatible to breast (MDA-MB-231) and ovarian (SKOV-3 and Caov-3) cancer cells after a four-hour incubation period. Fluorescence microscopy images demonstrated the ability of the nanoparticles to act as imaging agents in all three cell lines in as little as 1 hour. The results shown indicate the potential of these NIR-BODIPY-loaded nanoparticles as contrast agents for near-infrared optical imaging in cancer.Graphical abstract

  1. Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

    Hamon, Casey L.; Dorsey, Christopher L. [Texas State University, Department of Chemistry and Biochemistry (United States); Özel, Tuğba [Texas State University, Materials Science, Engineering, and Commercialization Program (United States); Barnes, Eugenia M.; Hudnall, Todd W.; Betancourt, Tania, E-mail: tb26@txstate.edu [Texas State University, Department of Chemistry and Biochemistry (United States)

    2016-07-15

    Nanoparticles are being readily investigated as carriers for the delivery of imaging and therapeutic agents for the detection, monitoring, and treatment of cancer and other diseases. In the present work, the preparation of biodegradable polymeric nanoparticles loaded with a near-infrared fluorescent aza-boron dipyrromethene (NIR-BODIPY) derivative, and their use as contrast agents for optical imaging in cancer are described. Nanoparticles were prepared by nanoprecipitation of amphiphilic block copolymers of poly(lactic acid) and poly(ethylene glycol). The size, morphology, dye loading, spectral properties, quantum yield, cytocompatibility, and in vitro NIR imaging potential of the nanoparticles in breast and ovarian cancer cells were evaluated. Spherical nanoparticles of 30–70 nm in diameter were loaded with 0.73 w/w% BODIPY derivative. At this loading, the dye presented a fluorescence quantum yield in the same order of magnitude as in solution. Nanoparticle suspensions at concentrations up to 580 μg/mL were cytocompatible to breast (MDA-MB-231) and ovarian (SKOV-3 and Caov-3) cancer cells after a four-hour incubation period. Fluorescence microscopy images demonstrated the ability of the nanoparticles to act as imaging agents in all three cell lines in as little as 1 hour. The results shown indicate the potential of these NIR-BODIPY-loaded nanoparticles as contrast agents for near-infrared optical imaging in cancer.Graphical abstract.

  2. Cancer cell-selective promoter recognition accompanies antitumor effect by glucocorticoid receptor-targeted gold nanoparticle

    Sau, Samaresh; Agarwalla, Pritha; Mukherjee, Sudip; Bag, Indira; Sreedhar, Bojja; Pal-Bhadra, Manika; Patra, Chitta Ranjan; Banerjee, Rajkumar

    2014-05-01

    Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied on the delivery of `exogenous' genes invoking gene knockdown or replacement. Practically, there are no instances for the nanoparticle-mediated promoter regulation of `endogenous' genes, more so, as a cancer selective phenomenon. In this regard, we report the development of a simple, easily modifiable GNP-formulation, which promoted/up-regulated the expression of a specific category of `endogenous' genes, the glucocorticoid responsive genes. This genetic up-regulation was induced in only cancer cells by modified GNP-mediated transcriptional activation of its cytoplasmic receptor, glucocorticoid receptor (GR). Normal cells and their GR remained primarily unperturbed by this GNP-formulation. The most potent gene up-regulating GNP-formulation down-regulated a cancer-specific proliferative signal, phospho-Akt in cancer cells, which accompanied retardation of tumor growth in the murine melanoma model. We show that GR-targeted GNPs may find potential use in the targeting and modulation of genetic information in cancer towards developing novel anticancer therapeutics.Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied

  3. Ultrastructural Analysis of Human Breast Cancer Cells during Their Overtime Interaction with Cerium Oxide Nanoparticles

    AlAbbadi, Shatha H.

    2016-12-01

    Cerium oxide nanoparticles have been proposed as an anticancer agent, thanks to their ability of tuning the redox activity in accordance to different conditions, which lead to selective roles on healthy and cancer cells. Recent evidence suggested the ability of these nanoparticles to be toxic against cancer cells, while confer protection from oxidative stress, toward healthy cells. The main focus of this study was to determine the ultrastructural effects of cerium oxide nanoparticles over multiple incubation time of 1, 3, and 7 days on breast healthy and cancer cells. Cellular characterizations were carried out using electron microscopes, both transmission and scanning electron microscopes, while the viability assessments were performed by propidium iodide and trypan blue viability assays. The obtained results of the viability assays and electron microscopy suggested higher toxic effects on the cancer cell line viability by using a nanoceria dose of 300 μg/mL after 1 day of treatment. Such effects were shown to be preserved at 3 days, and in a longer time point of 7 days. On the contrary, the healthy cells underwent less effects on their viability at time point of 1 and 7 days. The 3 days treatment demonstrated a reduction on the number of cells that did not correlate with an increase of the dead cells, which suggested a possible initial decrease of the cell growth rate, which could be due to the high intracellular loading of nanoparticles. To conclude, the overall result of this experiment suggested that 300 μg/mL of CeO2 nanoparticles is the most suitable dose, within the range and the time point tested, which induces long-lasting cytotoxic effects in breast cancer cells, without harming the normal cells, as highlighted by the viability assays and ultrastructural characterization of electron microscopy analysis.

  4. Oxygen microenvironment affects the uptake of nanoparticles in head and neck tumor cells

    Chen, Eunice Y.; Hodge, Sasson; Tai, Katherine; Hou, Huagang; Khan, Nadeem; Hoopes, P. Jack; Samkoe, Kimberley S.

    2013-02-01

    Survival of head and neck cancer patients has not improved in several decades despite advances in diagnostic and therapeutic techniques. Tumor hypoxia in head and neck cancers is a critical factor that leads to poor prognosis, resistance to radiation and chemotherapies, and increased metastatic potential. Magnetic nanoparticle hyperthermia (mNPHT) is a promising therapy for hypoxic tumors because nanoparticles (NP) can be directly injected into, or targeted to, hypoxic tumor cells and exposed to alternating magnetic fields (AMF) to induce hyperthermia. Magnetic NPHT can improve therapeutic effectiveness by two modes of action: 1) direct killing of hypoxic tumor cells; and 2) increase in tumor oxygenation, which has the potential to make the tumor more susceptible to adjuvant therapies such as radiation and chemotherapy. Prior studies in breast cancer cells demonstrated that a hypoxic microenvironment diminished NP uptake in vitro; however, mNPHT with intratumoral NP injection in hypoxic tumors increased tumor oxygenation and delayed tumor growth. In this study, head and neck squamous cell carcinoma (HNSCC) cell lines were incubated in normoxic, hypoxic, and hyperoxic conditions with iron oxide NP for 4-72 hours. After incubation, the cells were analyzed for iron uptake by mass spectrometry, Prussian blue staining, and electron microscopy. In contrast to breast cancer cells, uptake of NPs was increased in hypoxic microenvironments as compared to normoxic conditions in HNSCC cells. In future studies, we will confirm the effect of the oxygen microenvironment on NP uptake and efficacy of mNPHT both in vitro and in vivo.

  5. Low-magnetization magnetic microcapsules: A synergistic theranostic platform for remote cancer cells therapy and imaging

    Zhang, Wei

    2014-04-02

    Multifunctional magnetic microcapsules (MMCs) for the combined cancer cells hyperthermia and chemotherapy in addition to MR imaging are successfully developed. A classical layer-by-layer technique of oppositely charged polyelectrolytes (poly(allylamine hydrochloride) (PAH) and poly(4-styrene sulfonate sodium) (PSS)) is used as it affords great controllability over the preparation together with enhanced loading of the chemotherapeutic drug (doxorubicin, DOX) in the microcapsules. Superparamagnetic iron oxide (SPIOs) nanoparticles are layered in the system to afford MMC1 (one SPIOs layer) and MMC2 (two SPIOs layers). Most interestingly, MMC1 and MMC2 show efficient hyperthermia cell death and controlled DOX release although their magnetic saturation value falls below 2.5 emu g-1, which is lower than the 7-22 emu g-1 reported to be the minimum value needed for biomedical applications. Moreover, MMCs are pH responsive where a pH 5.5 (often reported for cancer cells) combined with hyperthermia increases DOX release predictably. Both systems prove viable when used as T2 contrast agents for MR imaging in HeLa cells with high biocompatibility. Thus, MMCs hold a great promise to be used commercially as a theranostic platform as they are controllably prepared, reproducibly enhanced, and serve as drug delivery, hyperthermia, and MRI contrast agents at the same time.

  6. Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study

    Reuveni T

    2011-11-01

    Full Text Available Tobi Reuveni1, Menachem Motiei1, Zimam Romman2, Aron Popovtzer3, Rachela Popovtzer11Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-ilan University, Ramat Gan, 2GE HealthCare, Tirat Hacarmel, 3Department of Otorhinolaryngology, Head and Neck Surgery and Onology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, IsraelAbstract: In recent years, advances in molecular biology and cancer research have led to the identification of sensitive and specific biomarkers that associate with various types of cancer. However, in vivo cancer detection methods with computed tomography, based on tracing and detection of these molecular cancer markers, are unavailable today. This paper demonstrates in vivo the feasibility of cancer diagnosis based on molecular markers rather than on anatomical structures, using clinical computed tomography. Anti-epidermal growth factor receptor conjugated gold nanoparticles (30 nm were intravenously injected into nude mice implanted with human squamous cell carcinoma head and neck cancer. The results clearly demonstrate that a small tumor, which is currently undetectable through anatomical computed tomography, is enhanced and becomes clearly visible by the molecularly-targeted gold nanoparticles. It is further shown that active tumor targeting is more efficient and specific than passive targeting. This noninvasive and nonionizing molecular cancer imaging tool can facilitate early cancer detection and can provide researchers with a new technique to investigate in vivo the expression and activity of cancer-related biomarkers and molecular processes.Keywords: functional computed tomography, molecular imaging, gold nanoparticles, biologically targeted in vivo imaging, contrast agents

  7. Triton X-100 functionalized Fe3O4 nanoparticles for biomedical applications

    Gawali, Santosh L.; Madan, Devendra P.; Barick, K. C.; Somani, R.; Hassan, P. A.

    2018-04-01

    We report the preparation of Triton X-100 functionalized Fe3O4 nanoparticles (TXMNPs) and investigated their potential application in hyperthermia therapy. The formation of highly crystalline, spinel-structured Fe3O4 nanoparticles of average size of about 10 nm was evident from X-ray diffraction (XRD) and transmission electron microscopy (TEM) analyses. Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), UV-visible spectroscopy and zeta-potential measurements suggest the successful functionalization of nanoparticles with TX-100. These TXMNPs exhibit good colloidal stabilization in aqueous medium and show protein resistance characteristic in physiological medium. They showed excellent heating efficacy under AC magnetic field (AMF) with specific absorption rate (SAR) values of 146 and 260 W/g of Fe for 1.25 and 0.625 mg/ml of Fe, respectively at an applied AMF of 507 Oe and frequency of 300 kHz. Thus, these nanoparticles can be used as effective thermoseed for hyperthermia treatment of cancer.

  8. Thermometry of hot spot using NMR for hyperthermia

    Amemiya, Yoshifumi; Kamimura, Yoshitsugu

    1983-01-01

    Lately noticed hyperthermia in cancer therapy requires non-invasive measurement of the temperature at the warmed site in the deep portion of human body. Nuclear magnetic relaxation time of NMR is also usable for cancer diagnosis. For coordination of these two techniques, it was judged suitable to measure temperature by NMR so that cancer diagnosis and treatment and evaluation of therapeutic effect might be incorporated into one system. This report dealt with concrete procedures of measuring the temperature of deep portions by NMR. Computations revealed that the coefficient of temperature of the thermal equilibrium magnetization was useful, that magnetic field focusing was the most effective imaging technique and that temperature rise in areas about 2 cm in radius could be measured without large errors. (Chiba, N.)

  9. Engineering nanoparticle-coated bacteria as oral DNA vaccines for cancer immunotherapy.

    Hu, Qinglian; Wu, Min; Fang, Chun; Cheng, Changyong; Zhao, Mengmeng; Fang, Weihuan; Chu, Paul K; Ping, Yuan; Tang, Guping

    2015-04-08

    Live attenuated bacteria are of increasing importance in biotechnology and medicine in the emerging field of cancer immunotherapy. Oral DNA vaccination mediated by live attenuated bacteria often suffers from low infection efficiency due to various biological barriers during the infection process. To this end, we herein report, for the first time, a new strategy to engineer cationic nanoparticle-coated bacterial vectors that can efficiently deliver oral DNA vaccine for efficacious cancer immunotherapy. By coating live attenuated bacteria with synthetic nanoparticles self-assembled from cationic polymers and plasmid DNA, the protective nanoparticle coating layer is able to facilitate bacteria to effectively escape phagosomes, significantly enhance the acid tolerance of bacteria in stomach and intestines, and greatly promote dissemination of bacteria into blood circulation after oral administration. Most importantly, oral delivery of DNA vaccines encoding autologous vascular endothelial growth factor receptor 2 (VEGFR2) by this hybrid vector showed remarkable T cell activation and cytokine production. Successful inhibition of tumor growth was also achieved by efficient oral delivery of VEGFR2 with nanoparticle-coated bacterial vectors due to angiogenesis suppression in the tumor vasculature and tumor necrosis. This proof-of-concept work demonstrates that coating live bacterial cells with synthetic nanoparticles represents a promising strategy to engineer efficient and versatile DNA vaccines for the era of immunotherapy.

  10. Preparation and Evaluation anticancer activity of D-glucosamine Nanoparticles on Metastatic cancer Model in vivo

    Neda Soleimani

    2016-07-01

    Full Text Available Objective(s: Breast cancer imposes a highest rate of malignancy among the women all around the world. Chitin and its derivatives such as D-glucosamine-carboxymethyl chitin and Di-hydroxy propyl chitin have immune-modulating effects and influence on innate and acquisitive immunity which lead to cell activity enhancement. The aim of this study was investigating the effect of D-glucosamine nanoparticle on immune responses such as the changes in cytokines type 1 and 2 level in tumoral mice. Methods: Nanoparticles were synthesized by ionic gelation method and characterized by DLS and SEM methods. Tumors were induced in experimental mice and subsequently treated with nanoparticles. Then, the production of cytokine interferon-γ (IFN-γ and interleukin 4 (IL-4 were evaluated. Results: The obtained results showed a significant increase in the level of IFN-γ production in the mice group treated with nanoparticles compared to control groups. Additionally, there was a reduction in the level of IL-4 and tumor size in the test group. Conclusions: D-glucosamine nanoparticles can be proposed as a stimulator of the immune system and a promising compound for cancer treatment in the future.

  11. pH-responsive mesoporous silica nanoparticles employed in controlled drug delivery systems for cancer treatment

    Yang, Ke-Ni; Zhang, Chun-Qiu; Wang, Wei; Wang, Paul C.; Zhou, Jian-Ping; Liang, Xing-Jie

    2014-01-01

    In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles (MSNs) with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanoparticles, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail

  12. Thermo-induced modifications and selective accumulation of glucose-conjugated magnetic nanoparticles in vivo in rats - increasing the effectiveness of magnetic-assisted therapy - pilot study.

    Traikov, L; Antonov, I; Gerou, A; Vesselinova, L; Hadjiolova, R; Raynov, J

    2015-09-01

    Ferro-Magnetic nanoparticles (Fe-MNP) have gained a lot of attention in biomedical and industrial applications due to their biocompatibility, ease of surface modification and paramagnetic properties. The basic idea of our study is whether it is possible to use glucose-conjugate Fe-MNP (Glc-Fe-MNP) for targeting and more accurate focusing in order to increase the effect of high-frequency electromagnetic fields induced hyperthermia in solid tumors. Tumors demonstrate high metabolic activity for glucose in comparison with other somatic cells.Increasing of accumulation of glucose conjugated (Glc)-Fe-MNP on tumor site and precision of radio frequency electro-magnetic field (RF-EMF) energy absorption in solid tumors, precede RF-EMF induced hyperthermia. Rat model for monitoring the early development of breast cancer. Twenty female Wistar rats (MU-line-6171) were divided into two groups of 10 rats that were either treated with N-methyl-N-nitrosourea to induce breast cancer