Magnetic hyperthermia with hard-magnetic nanoparticles

Energy Technology Data Exchange (ETDEWEB)

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.

Gelatine-assisted synthesis of magnetite nanoparticles for magnetic hyperthermia

Energy Technology Data Exchange (ETDEWEB)

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.

Magnetic nanoparticle hyperthermia as an adjuvant cancer therapy with chemotherapy

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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.

Thermosensitive Nanostructured Media for imaging and Hyperthermia Cancer Treatment

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Magnetic Nanoparticles Coated with a Thermosensitive Polymer with Hyperthermia Properties

Directory of Open Access Journals (Sweden)

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.

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

International Nuclear Information System (INIS)

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)

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

Directory of Open Access Journals (Sweden)

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

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

Directory of Open Access Journals (Sweden)

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.

Stabilization of temperature during magnetic hyperthermia by Ce substituted magnetite nanoparticles

Energy Technology Data Exchange (ETDEWEB)

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.

Biodegradable magnesium nanoparticle-enhanced laser hyperthermia therapy

Directory of Open Access Journals (Sweden)

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

Water dispersible superparamagnetic Cobalt iron oxide nanoparticles for magnetic fluid hyperthermia

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Magnetic Properties of Magnetic Nanoparticles for Efficient Hyperthermia

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Biological effects of hyperthermia

International Nuclear Information System (INIS)

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.)

Radiation therapy combined with hyperthermia in advanced cancer

International Nuclear Information System (INIS)

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)

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

Directory of Open Access Journals (Sweden)

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.

Self-regulated magnetic fluid hyperthermia: A potential cancer therapy

Science.gov (United States)

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

Current Status and Perspectives of Hyperthermia in Cancer Therapy

Science.gov (United States)

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.

Targeting therapy-resistant cancer stem cells by hyperthermia

DEFF Research Database (Denmark)

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...

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

Directory of Open Access Journals (Sweden)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

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

Directory of Open Access Journals (Sweden)

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.

Improved delivery of magnetic nanoparticles with chemotherapy cancer treatment

Science.gov (United States)

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.

Induction heating studies of combustion synthesized MgFe2O4 nanoparticles for hyperthermia applications

International Nuclear Information System (INIS)

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

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

Directory of Open Access Journals (Sweden)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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)

Feasibility study of local ultrasound hyperthermia in cancer therapy

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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

International Nuclear Information System (INIS)

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)

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

International Nuclear Information System (INIS)

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

Exchange-coupled Fe3O4/CoFe2O4 nanoparticles for advanced magnetic hyperthermia

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Iron oxide and gold nanoparticles in cancer therapy

Energy Technology Data Exchange (ETDEWEB)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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)

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Czech Academy of Sciences Publication Activity Database

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

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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.

Re-irradiation and hyperthermia after surgery for recurrent breast cancer

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Thermometric analysis of intra-cavitary hyperthermia for esophageal cancer.

Science.gov (United States)

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.

On the temperature control in self-controlling hyperthermia therapy

Energy Technology Data Exchange (ETDEWEB)

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.

On the temperature control in self-controlling hyperthermia therapy

International Nuclear Information System (INIS)

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.

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

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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)

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

Science.gov (United States)

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.

Multimodal treatment combining chemotherapy, hyperthermia and radiotherapy for ovarian cancer

International Nuclear Information System (INIS)

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.)

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

International Nuclear Information System (INIS)

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)

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

‘Smart’ gold nanoshells for combined cancer chemotherapy and hyperthermia

International Nuclear Information System (INIS)

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)

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

Hyperthermia quality assurance

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

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

KAUST Repository

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.

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

KAUST Repository

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.

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

International Nuclear Information System (INIS)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

NARCIS (Netherlands)

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

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

International Nuclear Information System (INIS)

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)

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

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

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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)

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

International Nuclear Information System (INIS)

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.

Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells

Directory of Open Access Journals (Sweden)

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.

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

International Nuclear Information System (INIS)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Indian Academy of Sciences (India)

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 ...

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

Energy Technology Data Exchange (ETDEWEB)

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.

Magnetic nanoparticle biodistribution following intratumoral administration

Energy Technology Data Exchange (ETDEWEB)

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.

Photo-fluorescent and magnetic properties of iron oxide nanoparticles for biomedical applications.

Science.gov (United States)

Shi, Donglu; Sadat, M E; Dunn, Andrew W; Mast, David B

2015-05-14

Iron oxide exhibits fascinating physical properties especially in the nanometer range, not only from the standpoint of basic science, but also for a variety of engineering, particularly biomedical applications. For instance, Fe3O4 behaves as superparamagnetic as the particle size is reduced to a few nanometers in the single-domain region depending on the type of the material. The superparamagnetism is an important property for biomedical applications such as magnetic hyperthermia therapy of cancer. In this review article, we report on some of the most recent experimental and theoretical studies on magnetic heating mechanisms under an alternating (AC) magnetic field. The heating mechanisms are interpreted based on Néel and Brownian relaxations, and hysteresis loss. We also report on the recently discovered photoluminescence of Fe3O4 and explain the emission mechanisms in terms of the electronic band structures. Both optical and magnetic properties are correlated to the materials parameters of particle size, distribution, and physical confinement. By adjusting these parameters, both optical and magnetic properties are optimized. An important motivation to study iron oxide is due to its high potential in biomedical applications. Iron oxide nanoparticles can be used for MRI/optical multimodal imaging as well as the therapeutic mediator in cancer treatment. Both magnetic hyperthermia and photothermal effect has been utilized to kill cancer cells and inhibit tumor growth. Once the iron oxide nanoparticles are up taken by the tumor with sufficient concentration, greater localization provides enhanced effects over disseminated delivery while simultaneously requiring less therapeutic mass to elicit an equal response. Multi-modality provides highly beneficial co-localization. For magnetite (Fe3O4) nanoparticles the co-localization of diagnostics and therapeutics is achieved through magnetic based imaging and local hyperthermia generation through magnetic field or photon

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

International Nuclear Information System (INIS)

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

Design of a temperature measurement and feedback control system based on an improved magnetic nanoparticle thermometer

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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)

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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

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

Directory of Open Access Journals (Sweden)

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

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Triton X-100 functionalized Fe3O4 nanoparticles for biomedical applications

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Hyperthermia for the Treatment of Locally Advanced Cervix Cancer

NARCIS (Netherlands)

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

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

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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

Cancer nanomedicine: gold nanoparticle mediated combined cancer therapy

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

Multimodal magnetic nano-carriers for cancer treatment: Challenges and advancements

Energy Technology Data Exchange (ETDEWEB)

Aadinath, W.; Ghosh, Triroopa; Anandharamakrishnan, C., E-mail: anandharam@cftri.res.in

2016-03-01

Iron oxide nanoparticles (IONPs) have been a propitious topic for cancer treatment in recent years because of its multifunctional theranostic applications under magnetic field. Two such widely used applications in cancer biology are gradient magnetic field guided targeting and alternative magnetic field (AMF) induced local hyperthermia. Gradient magnetic field guided targeting is a mode of active targeting of therapeutics conjugated with iron oxide nanoparticles. These particles also dissipate heat in presence of AMF which causes thermal injury to the cells of interest, for example tumour cells and subsequent death. Clinical trials divulge the feasibility of such magnetic nano-carrier as a promising candidate in cancer biology. However, these techniques need further investigations to curtail certain limitations manifested. Recent progresses in response have shrunken the barricade to certain extent. In this context, principles, challenges associated with these applications and recent efforts made in response will be discussed. - Highlights: • Iron oxide nanoparticles offer various modalities in the field of cancer theranostics. • Magnetic field guided targeting and local hyperthermia are two well known modalities in cancer therapy. • These techniques need further investigations to curtail certain limitations manifested. • This review emphasizes the recent efforts carried out to counteract the drawbacks.

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

Science.gov (United States)

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.

MWCNT-MnFe2O4 nanocomposite for efficient hyperthermia applications

Science.gov (United States)

Seal, Papori; Hazarika, Monalisa; Paul, Nibedita; Borah, J. P.

2018-04-01

In this work we present synthesis of multi-walled carbon nanotube (MWCNT)-Manganese ferrite (MnFe2O4) nanocomposite and its probable application in hyperthermia. MnFe2O4 nanoparticles were synthesized by co-precipitation method. X ray diffractogram (XRD) confirms the formation of cubic phase of MnFe2O4 with preferred crystallographic orientation along (311) plane. High resolution electron microscope (HRTEM) image of the composites confirms the presence of MnFe2O4 spherical nanoparticles on the surface of CNT which are bound strongly to the surface. MWCNT-MnFe2O4 nanocomposite were prepared after acid functionalization of MWCNT. Vibrational features of the synthesized samples were confirmed through Fourier transformed infra-red spectroscopy (FTIR). FTIR spectra of acid functionalized MWCNT shows a peak positioned at ˜1620cm-1 which corresponds to C=O functional group of carboxylic acid. Prepared MnFe2O4 nanoparticles and MWCNT-MnFe2O4 nanocomposites were subjected to hyperthermia studies.

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

International Nuclear Information System (INIS)

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)

Surface functionalized biocompatible magnetic nanospheres for cancer hyperthermia.

Energy Technology Data Exchange (ETDEWEB)

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.

Hormonal, Biochemical and Haematological Changes in Response to Acute Hyperthermia in Rabbits

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

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

Czech Academy of Sciences Publication Activity Database

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

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

Czech Academy of Sciences Publication Activity Database

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

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

Science.gov (United States)

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.

An overview of interstitial brachytherapy and hyperthermia

International Nuclear Information System (INIS)

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

Preferential radiosensitization of human prostatic carcinoma cells by mild hyperthermia

International Nuclear Information System (INIS)

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

Magnetic fluid hyperthermia probed by both calorimetric and dynamic hysteresis measurements

Energy Technology Data Exchange (ETDEWEB)

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.

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

Directory of Open Access Journals (Sweden)

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.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Numerical modeling for an electric-field hyperthermia applicator

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Simple and Rapid Synthesis of Magnetite/Hydroxyapatite Composites for Hyperthermia Treatments via a Mechanochemical Route

Science.gov (United States)

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

Simple and Rapid Synthesis of Magnetite/Hydroxyapatite Composites for Hyperthermia Treatments via a Mechanochemical Route

Directory of Open Access Journals (Sweden)

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.

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

Directory of Open Access Journals (Sweden)

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.

Magnetomotive Optical Coherence Elastography for Magnetic Hyperthermia Dosimetry Based on Dynamic Tissue Biomechanics

Science.gov (United States)

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

In Vivo Imaging of Local Gene Expression Induced by Magnetic Hyperthermia

Directory of Open Access Journals (Sweden)

Olivier Sandre

2017-02-01

Full Text Available The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and noninvasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected subcutaneously with Matrigel™ to generate so-called pseudotumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 h after heating. We showed that dextran-coated magnetic iron oxide nanoparticle dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as noninvasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

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

Science.gov (United States)

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.

Thermoresponsive magnetic composite nanomaterials for multimodal cancer therapy.

Science.gov (United States)

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.

Trial of radiation therapy combined with hyperthermia

Energy Technology Data Exchange (ETDEWEB)

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.

FDTD analysis of a noninvasive hyperthermia system for brain tumors.

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

Hyperthermia and radiotherapy

International Nuclear Information System (INIS)

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

Reirradiation + hyperthermia for recurrent breast cancer en cuirasse

Energy Technology Data Exchange (ETDEWEB)

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

Targeted nanoparticles for colorectal cancer

DEFF Research Database (Denmark)

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...

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

Institute of Scientific and Technical Information of China (English)

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.

Large specific absorption rates in the magnetic hyperthermia properties of metallic iron nanocubes

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

Nanomedicine for cancer therapy from chemotherapeutic to hyperthermia-based therapy

CERN Document Server

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. .

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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.

Fe3O4@Au composite magnetic nanoparticles modified with cetuximab for targeted magneto-photothermal therapy of glioma cells.

Science.gov (United States)

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.

FDTD analysis of a noninvasive hyperthermia system for brain tumors

Directory of Open Access Journals (Sweden)

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.

Advances in nanotheranostics II cancer theranostic nanomedicine

CERN Document Server

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...

Theranostic Iron Oxide/Gold Ion Nanoprobes for MR Imaging and Noninvasive RF Hyperthermia.

Science.gov (United States)

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.

Gold Nanoparticle Mediated Phototherapy for Cancer

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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

Magnetic nanoparticles for application in cancer therapy

Energy Technology Data Exchange (ETDEWEB)

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.

Magnetic nanoparticles for biomedical applications

International Nuclear Information System (INIS)

Krustev, P.; Ruskov, T.

2007-01-01

In this paper we describe different biomedical application using magnetic nanoparticles. Over the past decade, a number of biomedical applications have begun to emerge for magnetic nanoparticles of differing sizes, shapes, and compositions. Areas under investigation include targeted drug delivery, ultra-sensitive disease detection, gene therapy, high throughput genetic screening, biochemical sensing, and rapid toxicity cleansing. Magnetic nanoparticles exhibit ferromagnetic or superparamagnetic behavior, magnetizing strongly under an applied field. In the second case (superparamagnetic nanoparticles) there is no permanent magnetism once the field is removed. The superparamagnetic nanoparticles are highly attractive as in vivo probes or in vitro tools to extract information on biochemical systems. The optical properties of magnetic metal nanoparticles are spectacular and, therefore, have promoted a great deal of excitement during the last few decades. Many applications as MRI imaging and hyperthermia rely on the use of iron oxide particles. Moreover magnetic nanoparticles conjugated with antibodies are also applied to hyperthermia and have enabled tumor specific contrast enhancement in MRI. Other promising biomedical applications are connected with tumor cells treated with magnetic nanoparticles with X-ray ionizing radiation, which employs magnetic nanoparticles as a complementary radiate source inside the tumor. (authors)

Hyperthermia treatment planning

International Nuclear Information System (INIS)

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)

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

Directory of Open Access Journals (Sweden)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Combined effects of hyperthermia and radiation in cultured mammalian cells

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

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

Energy Technology Data Exchange (ETDEWEB)

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

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

International Nuclear Information System (INIS)

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

Citrate-capped gold nanoparticle electrophoretic heat production in response to a time-varying radiofrequency electric-field.

Science.gov (United States)

Corr, Stuart J; Raoof, Mustafa; Mackeyev, Yuri; Phounsavath, Sophia; Cheney, Matthew A; Cisneros, Brandon T; Shur, Michael; Gozin, Michael; McNally, Patrick J; Wilson, Lon J; Curley, Steven A

2012-11-15

The evaluation of heat production from gold nanoparticles (AuNPs) irradiated with radiofrequency (RF) energy has been problematic due to Joule heating of their background ionic buffer suspensions. Insights into the physical heating mechanism of nanomaterials under RF excitations must be obtained if they are to have applications in fields such as nanoparticle-targeted hyperthermia for cancer therapy. By developing a purification protocol which allows for highly-stable and concentrated solutions of citrate-capped AuNPs to be suspended in high-resistivity water, we show herein, for the first time, that heat production is only evident for AuNPs of diameters ≤ 10 nm, indicating a unique size-dependent heating behavior not previously observed. Heat production has also shown to be linearly dependent on both AuNP concentration and total surface area, and severely attenuated upon AuNP aggregation. These relationships have been further validated using permittivity analysis across a frequency range of 10 MHz to 3 GHz, as well as static conductivity measurements. Theoretical evaluations suggest that the heating mechanism can be modeled by the electrophoretic oscillation of charged AuNPs across finite length scales in response to a time-varying electric field. It is anticipated these results will assist future development of nanoparticle-assisted heat production by RF fields for applications such as targeted cancer hyperthermia.

Tuning the magnetism of ferrite nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Viñas, S. Liébana [Faculty of Physics and CENIDE, University Duisburg-Essen, Duisburg 47048 (Germany); Departamento de Física Aplicada, Universidade de Vigo, Vigo 36310 (Spain); Simeonidis, K. [Department of Physics, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Li, Z.-A.; Ma, Z. [Faculty of Physics and CENIDE, University Duisburg-Essen, Duisburg 47048 (Germany); Myrovali, E.; Makridis, A.; Sakellari, D. [Department of Physics, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Angelakeris, M., E-mail: agelaker@auth.gr [Department of Physics, Aristotle University of Thessaloniki, Thessaloniki 54124 (Greece); Wiedwald, U.; Spasova, M. [Faculty of Physics and CENIDE, University Duisburg-Essen, Duisburg 47048 (Germany); Farle, M., E-mail: michael.farle@uni-due.de [Faculty of Physics and CENIDE, University Duisburg-Essen, Duisburg 47048 (Germany)

2016-10-01

The importance of magnetic interactions within an individual nanoparticle or between adjacent ones is crucial not only for the macroscopic collective magnetic behavior but for the AC magnetic heating efficiency as well. On this concept, single-(MFe{sub 2}O{sub 4} where M=Fe, Co, Mn) and core–shell ferrite nanoparticles consisting of a magnetically softer (MnFe{sub 2}O{sub 4}) or magnetically harder (CoFe{sub 2}O{sub 4}) core and a magnetite (Fe{sub 3}O{sub 4}) shell with an overall size in the 10 nm range were synthesized and studied for their magnetic particle hyperthermia efficiency. Magnetic measurements indicate that the coating of the hard magnetic phase (CoFe{sub 2}O{sub 4}) by Fe{sub 3}O{sub 4} provides a significant enhancement of hysteresis losses over the corresponding single-phase counterpart response, and thus results in a multiplication of the magnetic hyperthermia efficiency opening a novel pathway for high-performance, magnetic hyperthermia agents. At the same time, the existence of a biocompatible Fe{sub 3}O{sub 4} outer shell, toxicologically renders these systems similar to iron-oxide ones with significantly milder side-effects. - Highlights: • Magnetic hyperthermia is studied for 10 nm single and core/shell ferrite nanoparticles. • Maximum heating rate is observed for Fe{sub 3}O{sub 4}-coated CoFe{sub 2}O{sub 4} nanoparticles. • The increase is attributed to the interaction of phases with different anisotropy. • The presence of biocompatible Fe{sub 3}O{sub 4} shell potentially minimizes toxic side-effects.

Engineering of gadofluoroprobes: Broad-spectrum applications from cancer diagnosis to therapy

Energy Technology Data Exchange (ETDEWEB)

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.

Engineering of gadofluoroprobes: Broad-spectrum applications from cancer diagnosis to therapy

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

Eight-MHz RF-hyperthermia for advanced urological malignancies

International Nuclear Information System (INIS)

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)

Novel thermo-sensitive core-shell nanoparticles for targeted paclitaxel delivery

International Nuclear Information System (INIS)

Li Yuanpei; Pan Shirong; Zhang Wei; Du Zhuo

2009-01-01

Novel thermo-sensitive nanoparticles self-assembled from poly(N,N-diethylacrylamide- co-acrylamide)-block-poly(γ-benzyl L-glutamate) were designed for targeted drug delivery in localized hyperthermia. The lower critical solution temperature (LCST) of nanoparticles was adjusted to a level between physiological body temperature (37 deg. C) and that used in local hyperthermia (about 43 deg. C). The temperature-dependent performances of the core-shell nanoparticles were systemically studied by nuclear magnetic resonance (NMR), circular dichroism (CD), fluorescence spectroscopy, dynamic light scattering (DLS), and atom force microscopy (AFM). The mean diameter of the nanoparticles increased slightly from 110 to 129 nm when paclitaxel (PTX), a poorly water-soluble anti-tumor drug, was encapsulated. A stability study in bovine serum albumin (BSA) solution indicated that the PTX loaded nanoparticles may have a long circulation time under physiological environments as the LCST was above physiological body temperature and the shell remained hydrophilic at 37 deg.C. The PTX release profiles showed thermo-sensitive controlled behavior. The proliferation inhibiting activity of PTX loaded nanoparticles was evaluated against Hela cells in vitro, compared with Taxol (a formulation of paclitaxel dissolved in Cremophor EL and ethanol). The cytotoxicity of PTX loaded nanoparticles increased obviously when hyperthermia was performed. The nanoparticles synthesized here could be an ideal candidate for thermal triggered anti-tumor PTX delivery system.

Thermal Skin Damage During Reirradiation and Hyperthermia Is Time-Temperature Dependent

Energy Technology Data Exchange (ETDEWEB)

Bakker, Akke, E-mail: akke.bakker@amc.uva.nl [Department of Radiation Oncology, Academic Medical Center (AMC), Amsterdam (Netherlands); Kolff, M. Willemijn [Department of Radiation Oncology, Academic Medical Center (AMC), Amsterdam (Netherlands); Holman, Rebecca [Clinical Research Unit, Academic Medical Center (AMC), Amsterdam (Netherlands); Leeuwen, Caspar M. van; Korshuize-van Straten, Linda; Kroon-Oldenhof, Rianne de; Rasch, Coen R.N.; Tienhoven, Geertjan van; Crezee, Hans [Department of Radiation Oncology, Academic Medical Center (AMC), Amsterdam (Netherlands)

2017-06-01

Purpose: To investigate the relationship of thermal skin damage (TSD) to time–temperature isoeffect levels for patients with breast cancer recurrence treated with reirradiation plus hyperthermia (reRT + HT), and to investigate whether the treatment history of previous treatments (scar tissue) is a risk factor for TSD. Methods and Materials: In this observational study, temperature characteristics of hyperthermia sessions were analyzed in 262 patients with recurrent breast cancer treated in the AMC between 2010 and 2014 with reirradiation and weekly hyperthermia for 1 hour. Skin temperature was measured using a median of 42 (range, 29-82) measurement points per hyperthermia session. Results: Sixty-eight patients (26%) developed 79 sites of TSD, after the first (n=26), second (n=17), third (n=27), and fourth (n=9) hyperthermia session. Seventy percent of TSD occurred on or near scar tissue. Scar tissue reached higher temperatures than other skin tissue (0.4°C, P<.001). A total of 102 measurement points corresponded to actual TSD sites in 35 of 79 sessions in which TSD developed. Thermal skin damage sites had much higher maximum temperatures than non-TSD sites (2.8°C, P<.001). Generalized linear mixed models showed that the probability of TSD is related to temperature and thermal dose values (P<.001) and that scar tissue is more at risk (odds ratio 0.4, P<.001). Limiting the maximum temperature of a measurement point to 43.7°C would mean that the probability of observing TSD was at most 5%. Conclusion: Thermal skin damage during reRT + HT for recurrent breast cancer was related to higher local temperatures and time–temperature isoeffect levels. Scar tissue reached higher temperatures than other skin tissue, and TSD occurred at lower temperatures and thermal dose values in scar tissue compared with other skin tissue. Indeed, TSD developed often on and around scar tissue from previous surgical procedures.

Quantifying the Combined Effect of Radiation Therapy and Hyperthermia in Terms of Equivalent Dose Distributions

International Nuclear Information System (INIS)

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

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

Czech Academy of Sciences Publication Activity Database

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

Oxygen microenvironment affects the uptake of nanoparticles in head and neck tumor cells

Science.gov (United States)

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.

Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells

Directory of Open Access Journals (Sweden)

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.

Thermo-induced modifications and selective accumulation of glucose-conjugated magnetic nanoparticles in vivo in rats - increasing the effectiveness of magnetic-assisted therapy - pilot study.

Science.gov (United States)

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 and 10 with carrageenan to induce inflammation (control). Glc-Fe-MNP can offer a solution to increase hyperthermia effect to the desired areas in the body by accumulation and increasing local concentration due to high tissue metabolic assimilation. In this condition, it is considered that the magnetization of the nanoparticles is a single-giant magnetic moment, the sum of all the individual magnetic moments and is proportional to the concentration of Glc-Fe-MNP.

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Hyaluronan and calcium carbonate hybrid nanoparticles for colorectal cancer chemotherapy

Science.gov (United States)

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.

Mechano-synthesis, structural and magnetic characterization, and heat release of α-Fe nanoparticles embedded in a wüstite matrix

Energy Technology Data Exchange (ETDEWEB)

Batista, S.O.S.; Morales, M.A.; Santos, W.C. dos; Iglesias, C.A. [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, 59078-900 Natal, RN (Brazil); Baggio-Saitovitch, E. [Centro Brasileiro de Pesquisas Físicas, Rua Dr. Xavier Sigaud 150, Urca, 22290-180 Rio de Janeiro, RJ (Brazil); Carriço, A.S. [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, 59078-900 Natal, RN (Brazil); Bohn, F., E-mail: felipebohn@gmail.com [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, 59078-900 Natal, RN (Brazil); Medeiros, S.N. de [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, 59078-900 Natal, RN (Brazil)

2015-10-01

We report a study of the structural and magnetic properties, as well as of the heat release, of an iron/wüstite composite, prepared from iron powder and water by high energy mechanical milling. We identify that the produced sample consists of α-Fe nanoparticles embedded in a wüstite matrix and has high stability in time. Moreover, we observe that it presents noticeable features, as exchange bias effect at low temperatures and, when an alternating magnetic field is applied, its temperature reaches ∼46 °C in ∼600 s. Thus, the results and the possibility of tuning the magnetic properties of α-Fe nanoparticles embedded in a wüstite matrix, through interface interactions, place this system as a very attractive candidate for biomedical applications such as magnetic hyperthermia agent for cancer therapy. - Highlights: • We investigate the structural and magnetic properties, as well as the heat release, of an iron/wüstite composite. • The samples are produced using high energy mechanical milling. • Fe nanoparticles embedded in a wüstite matrix have high stability in time. • When an alternating magnetic field is applied, the sample temperature increases up to ∼46°C. • The composite is an interesting candidate for biomedical applications, such as magnetic hyperthermia agent for cancer therapy.

Theranostic nanoparticles for the treatment of cancer

Science.gov (United States)

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.

Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

Science.gov (United States)

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

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

KAUST Repository

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].

Gold Nanoparticle Microwave Synthesis

Energy Technology Data Exchange (ETDEWEB)

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.

Gold Nanoparticle Microwave Synthesis

International Nuclear Information System (INIS)

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.

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

Science.gov (United States)

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.

Multifunctional superparamagnetic nanoparticles for enhanced drug transport in cystic fibrosis

Science.gov (United States)

Armijo, Leisha M.; Brandt, Yekaterina I.; Rivera, Antonio C.; Cook, Nathaniel C.; Plumley, John B.; Withers, Nathan J.; Kopciuch, Michael; Smolyakov, Gennady A.; Huber, Dale L.; Smyth, Hugh D.; Osinski, Marek

2012-10-01

Iron oxide colloidal nanoparticles (ferrofluids) are investigated for application in the treatment of cystic fibrosis lung infections, the leading cause of mortality in cystic fibrosis patients. We investigate the use of iron oxide nanoparticles to increase the effectiveness of administering antibiotics through aerosol inhalation using two mechanisms: directed particle movement in the presence of an inhomogeneous static external magnetic field and magnetic hyperthermia. Magnetic hyperthermia is an effective method for decreasing the viscosity of the mucus and biofilm, thereby enhancing drug, immune cell, and antibody penetration to the affected area. Iron oxide nanoparticles of various sizes and morphologies were synthesized and tested for specific losses (heating power). Nanoparticles in the superparamagnetic to ferromagnetic size range exhibited excellent heating power. Additionally, iron oxide / zinc selenide core/shell nanoparticles were prepared, in order to enable imaging of the iron oxide nanoparticles. We also report on synthesis and characterization of MnSe/ZnSeS alloyed quantum dots.

Orthogonal Clickable Iron Oxide Nanoparticle Platform for Targeting, Imaging, and On-Demand Release.

Science.gov (United States)

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.

Non-Invasive Radiofrequency Field Treatment to Produce Hepatic Hyperthermia: Efficacy and Safety in Swine

OpenAIRE

,; ,; ,; ,; ,; ,; ,; ,; ,

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...

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

KAUST Repository

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

Improving efficacy of hyperthermia in oncology by exploiting biological mechanisms

DEFF Research Database (Denmark)

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...

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

Science.gov (United States)

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.

Low-magnetization magnetic microcapsules: A synergistic theranostic platform for remote cancer cells therapy and imaging

KAUST Repository

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.

Oligonucleotide-based theranostic nanoparticles in cancer therapy

Science.gov (United States)

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

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

Science.gov (United States)

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.

31P-MRS study for the assessment of tumor response after radiotherapy and/or hyperthermia

International Nuclear Information System (INIS)

Kimura, Hirohiko; Itho, Satoshi; Nakatsugawa, Sigekazu; Maeda, Masayuki; Iwasaki, Toshiko; Yamamoto, Kazutaka; Ishii, Yasushi

1992-01-01

The metabolic changes of human lung cancer implanted in nude mice were studied by the use of in vivo 31 P nuclear magnetic resonance spectroscopy ( 31 P-MRS) after radiotherapy, hyperthermia or the combined therapy of radiation and hyperthermia. 31 P-MRS of the tumors showed increased Pi/β-NTP ratio and acidic pH value on 1 day after hyperthermia, that indicated metabolic decline caused by hyperthermia. On the other hand, lower Pi/β-NTP ratios during 3 to 10 days after irradiation suggested metabolic activation of the tumors. In the tumors treated with the combined therapy, 31 P-MRS revealed increase of Pi/β-NTP ratio within 1 day and its decrease subsequent 6 to 10 days after treatment, that indicated additive bi-phasic changes induced by radiation and hyperthermia, respectively. Since Pi/β-NTP ratio had significant correlation to the tumor blood perfusion measured by hydrogen gas clearance studies, these bi-phasic changes were considered to correspond to two different physiological states, namely, ischemic and reperfused states. 31 P-MRS obtained from tumors could be useful to asses the physiological consequence following radiation, hyperthermia or the combined therapy. (author)

Magnetic field enhanced photothermal effect of Fe3O4 nanoparticles

Science.gov (United States)

Pan, Pengfei; Lin, Yawen; Gan, Zhixing; Luo, Xiaobin; Zhou, Weiping; Zhang, Ning

2018-03-01

Photothermal and magnetothermal effects are promising in hyperthermia for cancer therapy. However, the development of safe treatments with limited side-effects requires a relatively-high thermal efficiency triggered by mild near-infrared (NIR) light and alternating magnetic field (HAC), which remains a formidable challenge. In this work, a magnetic field enhanced photothermal effect (MFEP) of Fe3O4 nanoparticles is proposed and investigated systematically. The results suggest remarkable temperature increments of 9.59 to 36.90 °C under irradiation of NIR with different light power densities (808 nm, 0-6.98 W/cm2) combined with a certain magnetic field (HAC = 1.5 kA/m at 90 kHz). The rise of temperature induced by MFEP is substantially larger than the sum of isolated photothermal and magnetothermal effects, which is attributed to the hot-phonon bottleneck effect. The MFEP of Fe3O4 nanoparticles could serve as an effective treatment for cancer therapy in the future.

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

Directory of Open Access Journals (Sweden)

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.

Using Nanoparticles in Medicine for Liver Cancer Imaging

Directory of Open Access Journals (Sweden)

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.

Noble Metal Nanoparticles Applications in Cancer

Directory of Open Access Journals (Sweden)

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.

Multifunctional nanoparticles for prostate cancer therapy.

Science.gov (United States)

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.

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

OpenAIRE

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...

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

Science.gov (United States)

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.

Magnetic hyperthermia dosimetry by biomechanical properties revealed in magnetomotive optical coherence elastography (MM-OCE) (Conference Presentation)

Science.gov (United States)

Huang, Pin-Chieh; Marjanovic, Marina; Spillman, Darold R.; Odintsov, Boris M.; Boppart, Stephen A.

2016-03-01

Magnetic nanoparticles (MNPs) have been utilized in magnetic hyperthermia to treat solid tumors. Under an appropriate AC magnetic field, energy can be transferred to the MNPs to heat up the intended tissue target while sparing non-targeted healthy tissue. However, a sensitive monitoring technique for the dose of MNP thermal therapy is desirable in order to prevent over-treatment and collateral injury. Typical hyperthermia dosimetry often relies on changes in imaging properties or temperature measurements based on the thermal distribution. Alternative dosimetric indicators can include the biomechanical properties of the tissue, reflecting the changes due to protein denaturation, coagulation, and tissue dehydration during hyperthermia treatments. Tissue stiffness can be probed by elastography modalities including MRI, ultrasound imaging, and optical coherence elastography (OCE), with OCE showing the highest displacement sensitivity (tens of nanometers). Magnetomotive optical coherence elastography (MM-OCE) is one type of OCE that utilizes MNPs as internal force transducers to probe the tissue stiffness. Therefore, we examined the feasibility of evaluating the hyperthermia dose based on the elasticity changes revealed by MM-OCE. Superparamagnetic MNPs were applied to ex vivo tissue specimens for both magnetic hyperthermia and MM-OCE experiments, where temperature and elastic modulus were obtained. A correlation between temperature rise and measured stiffness was observed. In addition, we found that with repetitive sequential treatments, tissue stiffness increased, while temperature rise remained relatively constant. These results potentially suggest that MM-OCE could indicate the irreversible changes the tissue undergoes during thermal therapy, which supports the idea for MM-OCE-based hyperthermia dosage control in future applications.

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

Science.gov (United States)

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.

Multifunctional nanoparticle developments in cancer diagnosis and treatment

Directory of Open Access Journals (Sweden)

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

Multifunctional Polymer Nanoparticles for Dual Drug Release and Cancer Cell Targeting

Directory of Open Access Journals (Sweden)

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.

A thermocouple thermometry system for ultrasound hyperthermia

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

Hyperthermia with rotating magnetic nanowires inducing heat into tumor by fluid friction

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

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

Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

Science.gov (United States)

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

Multifunctional gold nanoparticles for photodynamic therapy of cancer

Science.gov (United States)

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

The effect of hyperthermia in the preoperative combined treatment of radiation, hyperthermia and chemotherapy for rectal carcinoma

Energy Technology Data Exchange (ETDEWEB)

Konishi, Fumio; Furuta, Kazuhiro; Saito, Yukio; Kataoka, Takashi; Kashiwagi, Hiroshi; Okada, Masaki; Kanazawa, Kyotaro; Sugahara, Tadashi; Shinohara, Naohiro (Jichi Medical School, Minamikawachi, Tochigi (Japan))

1994-03-01

To investigate the effectiveness of hyperthermia in the preoperative combined treatment of radiation, chemotherapy and hyperthermia for rectal carcinoma, two groups were compared. Group A consisted of 18 patients in whom hyperthermia, radiation and chemotherapy were performed. Group B consisted of 18 patients in whom only chemotherapy and radiation were performed. The total dose of radiation in both of the two groups was 40.5 Gy, and a radiation field covering the whole pelvis was used. Hyperthermia was performed using 8 MHz radiofrequency waves (Thermotron RF8, Yamamoto Vinyter, Japan), and tumors were heated at about 42 degrees C for 50 minutes. Hyperthermia was repeated five times during the preoperative treatment. Chemotherapy was performed by giving 5-fluorouracil suppositories to a total dose of 3400 mg. Mean tumor reduction rates on barium enema were 31.8% in group A and 18.2% in group B. The difference was statistically significant. The result of the histological assessment of tumor necrosis showed that there was a significantly higher degree of necrosis in group A than in group B. These results showed that the addition of hyperthermia enhanced tumor necrosis. It was concluded that the addition of hyperthermia would be an effective preoperative treatment of rectal carcinoma. (author).

The effect of hyperthermia in the preoperative combined treatment of radiation, hyperthermia and chemotherapy for rectal carcinoma

International Nuclear Information System (INIS)

Konishi, Fumio; Furuta, Kazuhiro; Saito, Yukio; Kataoka, Takashi; Kashiwagi, Hiroshi; Okada, Masaki; Kanazawa, Kyotaro; Sugahara, Tadashi; Shinohara, Naohiro

1994-01-01

To investigate the effectiveness of hyperthermia in the preoperative combined treatment of radiation, chemotherapy and hyperthermia for rectal carcinoma, two groups were compared. Group A consisted of 18 patients in whom hyperthermia, radiation and chemotherapy were performed. Group B consisted of 18 patients in whom only chemotherapy and radiation were performed. The total dose of radiation in both of the two groups was 40.5 Gy, and a radiation field covering the whole pelvis was used. Hyperthermia was performed using 8 MHz radiofrequency waves (Thermotron RF8, Yamamoto Vinyter, Japan), and tumors were heated at about 42 degrees C for 50 minutes. Hyperthermia was repeated five times during the preoperative treatment. Chemotherapy was performed by giving 5-fluorouracil suppositories to a total dose of 3400 mg. Mean tumor reduction rates on barium enema were 31.8% in group A and 18.2% in group B. The difference was statistically significant. The result of the histological assessment of tumor necrosis showed that there was a significantly higher degree of necrosis in group A than in group B. These results showed that the addition of hyperthermia enhanced tumor necrosis. It was concluded that the addition of hyperthermia would be an effective preoperative treatment of rectal carcinoma. (author)

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

Energy Technology Data Exchange (ETDEWEB)

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

Selenium nanoparticles: potential in cancer gene and drug delivery.

Science.gov (United States)

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.

Transient mild hyperthermia induces E-selectin mediated localization of mesoporous silicon vectors in solid tumors.

Directory of Open Access Journals (Sweden)

Dickson K Kirui

Full Text Available BACKGROUND: Hyperthermia treatment has been explored as a strategy to overcome biological barriers that hinder effective drug delivery in solid tumors. Most studies have used mild hyperthermia treatment (MHT to target the delivery of thermo-sensitive liposomes carriers. Others have studied its application to permeabilize tumor vessels and improve tumor interstitial transport. However, the role of MHT in altering tumor vessel interfacial and adhesion properties and its relationship to improved delivery has not been established. In the present study, we evaluated effects of MHT treatment on tumor vessel flow dynamics and expression of adhesion molecules and assessed enhancement in particle localization using mesoporous silicon vectors (MSVs. We also determined the optimal time window at which maximal accumulation occur. RESULTS: In this study, using intravital microscopy analyses, we showed that temporal mild hyperthermia (∼1 W/cm(2 amplified delivery and accumulation of MSVs in orthotopic breast cancer tumors. The number of discoidal MSVs (1000×400 nm adhering to tumor vasculature increased 6-fold for SUM159 tumors and 3-fold for MCF-7 breast cancer tumors. By flow chamber experiments and Western blotting, we established that a temporal increase in E-selectin expression correlated with enhanced particle accumulation. Furthermore, MHT treatment was shown to increase tumor perfusion in a time-dependent fashion. CONCLUSIONS: Our findings reveal that well-timed mild hyperthermia treatment can transiently elevate tumor transport and alter vascular adhesion properties and thereby provides a means to enhance tumor localization of non-thermally sensitive particles such as MSVs. Such enhancement in accumulation could be leveraged to increase therapeutic efficacy and reduce drug dosing in cancer therapy.

The role of cobalt ferrite magnetic nanoparticles in medical science

International Nuclear Information System (INIS)

Amiri, S.; Shokrollahi, H.

2013-01-01

The nanotechnology industry is rapidly growing and promises that the substantial changes that will have significant economic and scientific impacts be applicable to a wide range of areas, such as aerospace engineering, nano-electronics, environmental remediation and medical healthcare. In this area, cobalt ferrite nanoparticles have been regarded as one of the competitive candidates because of their suitable physical, chemical and magnetic properties like the high anisotropy constant, high coercivity and high Curie temperature, moderate saturation magnetization and ease of synthesis. This paper introduces the magnetic properties, synthesis methods and some medical applications, including the hyperthermia, magnetic resonance imaging (MRI), magnetic separation and drug delivery of cobalt ferrite nanoparticles. Highlights: ► Cobalt ferrite nanoparticles are one of the most important materials for nanomedicine. ► They have high coercivity and moderate saturation magnetization. ► Cobalt ferrite nanoparticles are synthesized easily. ► They are a good candidate for hyperthermia and magnetic resonance imaging.

The role of cobalt ferrite magnetic nanoparticles in medical science

Energy Technology Data Exchange (ETDEWEB)

Amiri, S.; Shokrollahi, H., E-mail: Shokrollahi@sutech.ac.ir

2013-01-01

The nanotechnology industry is rapidly growing and promises that the substantial changes that will have significant economic and scientific impacts be applicable to a wide range of areas, such as aerospace engineering, nano-electronics, environmental remediation and medical healthcare. In this area, cobalt ferrite nanoparticles have been regarded as one of the competitive candidates because of their suitable physical, chemical and magnetic properties like the high anisotropy constant, high coercivity and high Curie temperature, moderate saturation magnetization and ease of synthesis. This paper introduces the magnetic properties, synthesis methods and some medical applications, including the hyperthermia, magnetic resonance imaging (MRI), magnetic separation and drug delivery of cobalt ferrite nanoparticles. Highlights: Black-Right-Pointing-Pointer Cobalt ferrite nanoparticles are one of the most important materials for nanomedicine. Black-Right-Pointing-Pointer They have high coercivity and moderate saturation magnetization. Black-Right-Pointing-Pointer Cobalt ferrite nanoparticles are synthesized easily. Black-Right-Pointing-Pointer They are a good candidate for hyperthermia and magnetic resonance imaging.

Combined treatment of 8 MHz radiofrequency hyperthermia and irradiation for advanced urological malignancies

International Nuclear Information System (INIS)

Nakajima, Kazuyoshi; Hisazumi, Haruo; Yamamoto, Hajime; Naito, Katsusuke; Misaki, Toshimitsu; Kobashi, Kazunori; Yokoyama, Osamu; Saito, Yasuo

1986-01-01

A combined therapy of irradiation and 8 MHz radiofrequency hyperthermia using Thermotron-RF Model 8 was carried out in a total of 26 patients with urological malignancies; 9 renal cancers, 1 renal capsular tumor, multiple liver metastatic lesions of renal cancer, a postoperative mediastinal metastasis of renal cancer, 2 ureteral cancers associated with bladder cancers, 4 bladder cancers, 4 prostatic cancers, a postoperative local recurrent tumor of an adult type Wilms' tumor, and multiple skin metastatic lesions of a penile cancer. Previous therapies were unsuccessful, or surgical interventions were not indicated because of poor general conditions. They were irradiated with daily 1.8 to 2.0 Gy, 5 times a week, or daily 2.0 to 4.0 Gy twice a week. Hyperthermia was induced twice a week within one hour after each irradiation, in total 10 times for 5 weeks. Intratumoral temperature was kept between 42.0 to 44.0 deg C. Clinical efficacy was evaluated by CT, ultrasound and biochemical data. Partial tumor regression, defined as the regression of 50 % or more, was obtained in one of the 9 renal cancers, in the mediastinal metastasis of renal cancer, 2 of the 4 prostatic cancers, one of the 4 bladder cancers and the 2 ureteral cancers, CR was obtained in the 2 associated bladder cancers. As side effects, a mild skin burns and anorexia were observed in approximately 50 % of the cases. Subcutaneous fat tissue indurations occurred in 6 of the 30 patients, who had 15 mm or more thickness of subdermal fat tissues, after treatment. (author)

Hyperthermia and hyperglycemia in oncology

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

Radiosensitizing Silica Nanoparticles Encapsulating Docetaxel for Treatment of Prostate Cancer.

Science.gov (United States)

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.

Magnetic nanoparticles for theragnostics

Science.gov (United States)

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

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

Science.gov (United States)

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.

Drug Delivery Nanoparticles in Skin Cancers

Science.gov (United States)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Science.gov (United States)

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

Thermometry of hot spot using NMR for hyperthermia

International Nuclear Information System (INIS)

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.)

Skin-safe photothermal therapy enabled by responsive release of acid-activated membrane-disruptive polymer from polydopamine nanoparticle upon very low laser irradiation.

Science.gov (United States)

Zhu, Rui; Gao, Feng; Piao, Ji-Gang; Yang, Lihua

2017-07-25

How to ablate tumor without damaging skin is a challenge for photothermal therapy. We, herein, report skin-safe photothermal cancer therapy provided by the responsive release of acid-activated hemolytic polymer (aHLP) from the photothermal polydopamine (PDA) nanoparticle upon irradiation at very low dosage. Upon skin-permissible irradiation (via an 850 nm laser irradiation at the power density of 0.4 W cm -2 ), the nanoparticle aHLP-PDA generates sufficient localized-heat to bring about mild hyperthermia treatment and consequently, responsively sheds off the aHLP polymer from its PDA nanocore; this leads to selective cytotoxicity to cancer cells under the acidic conditions of the extracellular microenvironment of tumor. As a result, our aHLP-PDA nanoparticle upon irradiation at a low dosage effectively inhibits tumor growth without damaging skin, as demonstrated using animal models. Effective in mitigating the otherwise inevitable skin damage in tumor photothermal therapy, the nanosystem reported herein offers an efficient pathway towards skin-safe photothermal therapy.

Development and characterization of multifunctional nanoparticles for drug delivery to cancer cells

Science.gov (United States)

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

A JASTRO study group report. A randomized phase III trial of hyperthermia in combination with radiotherapy for superficial tumors

International Nuclear Information System (INIS)

Hiraoka, Masahiro; Nishimura, Yasumasa; Mitsumori, Michihide

1998-01-01

Result of study about local effect of hyperthermia in combination with radiotherapy for superficial tumors was reported. The irradiation was more than 90% isodose for lesion, and total dose was 60 Gy in cases with anamnesis and 40-50 Gy and without anamnesis at a rate of five times a week and 2 Gy at one time. Hyperthermia was carried out four times; once a week, at 42.5 degrees on tumor side edge, and for 40 minutes. Total 53 cases (neck lymph node metastasis 30 cases, relapse breast cancer 11, advanced breast cancer 1, other superficial tumor 11) were divided into 2 groups. Radiotherapy without hyperthermia (group R) was 27 cases, radiotherapy with hyperthermia (group H) was 26 cases. CR and CR+PR within 2 months after treatment were as follows: Group R: 50%, 85%, Group H: 64%, 100%. The CR+PR was superior in group H (p=0.0497). The CR at maximum effect after treatment was 65% of group R and 86% of group H (p=0.17). The local control rate after CR was not different in both groups. (K.H.)

Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids.

Science.gov (United States)

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.

Optimal design of implants for magnetically mediated hyperthermia: A wireless power transfer approach

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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

Hyperthermia in low aspect-ratio magnetic nanotubes for biomedical applications

Science.gov (United States)

Gutierrez-Guzman, D. F.; Lizardi, L. I.; Otálora, J. A.; Landeros, P.

2017-03-01

A simple model for the magnetization reversal process of low aspect-ratio ferromagnetic nanotubes (MNTs) is presented. Because of advantages over other geometries, these structures are interesting for biomedical applications, such as magnetic hyperthermia cancer therapy, where the heat released during magnetic reversal is used to destroy tumors. For example, the tubular geometry provides two independent functional surfaces that may be selectively manipulated and also gives a storage cavity. Owing to their large surface to weight ratio and low mass density, MNTs are not decanted by gravity. We calculated magnetic phase diagrams, energy barriers, nucleation fields, and the amount of dissipated heat and specific absorption rate for magnetite nanotubes. The geometrical parameters were varied, and simple formulae were used to optimize the tube response under alternating excitation, as required for magnetic hyperthermia applications.

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

International Nuclear Information System (INIS)

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

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

International Nuclear Information System (INIS)

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)

Application of gold nanoparticles for gastrointestinal cancer theranostics: A systematic review.

Science.gov (United States)

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.

Analysis of clinical data to determine the minimum number of sensors required for adequate skin temperature monitoring of superficial hyperthermia treatments.

Science.gov (United States)

Bakker, Akke; Holman, Rebecca; Rodrigues, Dario B; Dobšíček Trefná, Hana; Stauffer, Paul R; van Tienhoven, Geertjan; Rasch, Coen R N; Crezee, Hans

2018-04-27

Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients. Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23 × 2 Gy) and hyperthermia using single 434 MHz applicators (effective field size 351-396 cm 2 ). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset simulating continuous thermal mapping of the skin. Temperature differences (ΔT) between subsets and complete sets of sensors were evaluated in terms of overall minimum (T min ) and maximum (T max ) temperature, as well as T90 and T10. Eighty patients were included yielding a total of 400 hyperthermia sessions. Median ΔT was 50 sensors were used. Subsets of sensors result in underestimation of T max up to -2.1 °C (ΔT 95%CI), which decreased to -0.5 °C when >50 sensors were used. Thermal profiles (8-21 probes) yielded a median ΔT 50 stationary sensors or thermal profiles. Adequate coverage of the skin temperature distribution during superficial hyperthermia treatment requires the use of >50 stationary sensors per 400 cm 2 applicator. Thermal mapping is a valid alternative.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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.

Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

Directory of Open Access Journals (Sweden)

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.

Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

Science.gov (United States)

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

Theoretical predictions for spatially-focused heating of magnetic nanoparticles guided by magnetic particle imaging field gradients

Energy Technology Data Exchange (ETDEWEB)

Dhavalikar, Rohan [Department of Chemical Engineering, University of Florida, 1030 Center Drive, Gainesville, FL 32611 (United States); Rinaldi, Carlos, E-mail: carlos.rinaldi@bme.ufl.edu [Department of Chemical Engineering, University of Florida, 1030 Center Drive, Gainesville, FL 32611 (United States); J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Drive, Gainesville, FL 32611 (United States)

2016-12-01

Magnetic nanoparticles in alternating magnetic fields (AMFs) transfer some of the field's energy to their surroundings in the form of heat, a property that has attracted significant attention for use in cancer treatment through hyperthermia and in developing magnetic drug carriers that can be actuated to release their cargo externally using magnetic fields. To date, most work in this field has focused on the use of AMFs that actuate heat release by nanoparticles over large regions, without the ability to select specific nanoparticle-loaded regions for heating while leaving other nanoparticle-loaded regions unaffected. In parallel, magnetic particle imaging (MPI) has emerged as a promising approach to image the distribution of magnetic nanoparticle tracers in vivo, with sub-millimeter spatial resolution. The underlying principle in MPI is the application of a selection magnetic field gradient, which defines a small region of low bias field, superimposed with an AMF (of lower frequency and amplitude than those normally used to actuate heating by the nanoparticles) to obtain a signal which is proportional to the concentration of particles in the region of low bias field. Here we extend previous models for estimating the energy dissipation rates of magnetic nanoparticles in uniform AMFs to provide theoretical predictions of how the selection magnetic field gradient used in MPI can be used to selectively actuate heating by magnetic nanoparticles in the low bias field region of the selection magnetic field gradient. Theoretical predictions are given for the spatial decay in energy dissipation rate under magnetic field gradients representative of those that can be achieved with current MPI technology. These results underscore the potential of combining MPI and higher amplitude/frequency actuation AMFs to achieve selective magnetic fluid hyperthermia (MFH) guided by MPI. - Highlights: • SAR predictions based on a field-dependent magnetization relaxation model. �

Hyperthermia and chemotherapy agent

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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.

Bimodal distribution of the magnetic dipole moment in nanoparticles with a monomodal distribution of the physical size

NARCIS (Netherlands)

van Rijssel, Jozef; Kuipers, Bonny W M; Erne, Ben

2015-01-01

High-frequency applications of magnetic nanoparticles, such as therapeutic hyperthermia and magnetic particle imaging, are sensitive to nanoparticle size and dipole moment. Usually, it is assumed that magnetic nanoparticles with a log-normal distribution of the physical size also have a log-normal

Thermal dosimetry for bladder hyperthermia treatment. An overview.

Science.gov (United States)

Schooneveldt, Gerben; Bakker, Akke; Balidemaj, Edmond; Chopra, Rajiv; Crezee, Johannes; Geijsen, Elisabeth D; Hartmann, Josefin; Hulshof, Maarten C C M; Kok, H Petra; Paulides, Margarethus M; Sousa-Escandon, Alejandro; Stauffer, Paul R; Maccarini, Paolo F

2016-06-01

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

Temperature responsive hydrogel magnetic nanocomposites for hyperthermia and metal extraction applications

Energy Technology Data Exchange (ETDEWEB)

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.

Temperature responsive hydrogel magnetic nanocomposites for hyperthermia and metal extraction applications

International Nuclear Information System (INIS)

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

Drug loaded magnetic nanoparticles for cancer therapy

International Nuclear Information System (INIS)

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

Hyperthermic effect of magnetic nanoparticles under electromagnetic field

Directory of Open Access Journals (Sweden)

Giovanni Baldi

2009-06-01

Full Text Available Magnetic nanoparticles have attracted increasingly attention due to their potential applications in many industrial fields, even extending their use in biomedical applications. In the latter contest the main features of magnetic nanoparticles are the possibility to be driven by external magnetic fields, the ability to pass through capillaries without occluding them and to absorb and convert electromagnetic radiation in to heat (Magnetic Fluid Hyperthermia. The main challenges of the current works on hyperthermia deal with the achievement of highly efficiency magnetic nanoparticles, the surface grafting with ligands able to facilitate their specific internalisation in tumour cells and the design of stealth nanocomposites able to circulate in the blood compartment for a long time. This article presents the synthesis of cobalt ferrite nanoparticles dispersed in diethylene glycol via the so called polyol strategy and the crystal size control through successive synthesis steps. Preliminary heat dissipation evaluations on the prepared samples were carried out and the question of how particles sizes affect their magnetic and hyperthermic properties was addressed as well. Furthermore we will present how surface chemistry can be modified in order to change the dispersity of the product without affecting magnetic and hyperthermic properties.

Nano-biomedical approaches of cancer therapy using carbon based and magnetic nanomaterials

Science.gov (United States)

Karmakar, Alokita

the higher accumulation EGF targeted SWCNTs to PANC-1 cells. In chapter 4, we have explored the multimodality of nanotechnology by using EGF-functionalized iron cored, carbon shelled (FeC) magnetic nanoprticle that can generate heat when exposed to radiofrequency (RF). This process called hyperthermia, which is an effective way to kill different cancer cells as cancer cells are most susceptible to heat increase beyond a threshold level compared to normal cells. By targeting the nanoparticles this process was made more efficient by selectively populating magnetic nanoparticles specifically in cancer cells only. Two different cells line, MCF-7 and PANC-1 were incubated with the magnetic nanopartilces for 24 hours followed by exposure to the RF (350KHz, 5kW) for 10 min. EB/AO and flow-cytometry were used to determine the apoptotic and necrotic cells. EGF targeted FeC was superior in apoptosis induction in both cell lines, while the untargeted nanoparticles showed little effect. The MCF-7 cells were more vulnerable to the targeted FeC nanoparticles compared to PANC-1 cells. Caspase-8 and caspase-3 assays were done to provide the involvement of these two capsizes in two different cell lines. To enhance the therapeutic efficiency of anticancer drug, two FDA approved anticancer drugs doxorubicin and erlotinib were loaded on FeC nanoparticles (Chapter 5). The loading capacity was determined by UV-Vis spectroscopy. MTT assay was also used to determine the loaded and unloaded forms of drug. RF treatment was used to generate hyperthermia and which also helps in releasing the drug from nanoparticles. Flow-cytomertic detection of apoptosis showed above 90% cells died after combined hyperthermia and doxorubicin treatment. Graphene is a 2D carbon nanoparticle that has been proven to be an excellent carrier of chemotherapeutic drugs. In chapter 6, -COOH functionalized graphene (FG) was used to deliver a potent but extremely hydrophobic and water insoluble drug, parthenolide (PTL), to

Applications of nanoparticles in cancer detection and diagnostic tool for hepatocellular carcinoma

International Nuclear Information System (INIS)

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)

FDTD verification of deep-set brain tumor hyperthermia using a spherical microwave source distribution

Energy Technology Data Exchange (ETDEWEB)

Dunn, D. [20th Intelligence Squadron, Offutt AFB, NE (United States); Rappaport, C.M. [Northeastern Univ., Boston, MA (United States). Center for Electromagnetics Research; Terzuoli, A.J. Jr. [Air Force Inst. of Tech., Dayton, OH (United States). Graduate School of Engineering

1996-10-01

Although use of noninvasive microwave hyperthermia to treat cancer is problematic in many human body structures, careful selection of the source electric field distribution around the entire surface of the head can generate a tightly focused global power density maximum at the deepest point within the brain. An analytic prediction of the optimum volume field distribution in a layered concentric head model based on summing spherical harmonic modes is derived and presented. This ideal distribution is then verified using a three-dimensional finite difference time domain (TDTD) simulation with a discretized, MRI-based head model excited by the spherical source. The numerical computation gives a very similar dissipated power pattern as the analytic prediction. This study demonstrates that microwave hyperthermia can theoretically be a feasible cancer treatment modality for tumors in the head, providing a well-resolved hot-spot at depth without overheating any other healthy tissue.

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

Science.gov (United States)

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.

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

International Nuclear Information System (INIS)

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

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

Energy Technology Data Exchange (ETDEWEB)

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.

Modelling Nanoparticle Diffusion into Cancer Tumors

Science.gov (United States)

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.

A numerical study on dual-phase-lag model of bio-heat transfer during hyperthermia treatment.

Science.gov (United States)

Kumar, P; Kumar, Dinesh; Rai, K N

2015-01-01

The success of hyperthermia in the treatment of cancer depends on the precise prediction and control of temperature. It was absolutely a necessity for hyperthermia treatment planning to understand the temperature distribution within living biological tissues. In this paper, dual-phase-lag model of bio-heat transfer has been studied using Gaussian distribution source term under most generalized boundary condition during hyperthermia treatment. An approximate analytical solution of the present problem has been done by Finite element wavelet Galerkin method which uses Legendre wavelet as a basis function. Multi-resolution analysis of Legendre wavelet in the present case localizes small scale variations of solution and fast switching of functional bases. The whole analysis is presented in dimensionless form. The dual-phase-lag model of bio-heat transfer has compared with Pennes and Thermal wave model of bio-heat transfer and it has been found that large differences in the temperature at the hyperthermia position and time to achieve the hyperthermia temperature exist, when we increase the value of τT. Particular cases when surface subjected to boundary condition of 1st, 2nd and 3rd kind are discussed in detail. The use of dual-phase-lag model of bio-heat transfer and finite element wavelet Galerkin method as a solution method helps in precise prediction of temperature. Gaussian distribution source term helps in control of temperature during hyperthermia treatment. So, it makes this study more useful for clinical applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Drug loaded silica coated MnFe2O4 ferromagnetic biomaterials for targeted cancer treatment

Science.gov (United States)

Anand, Vikas; Singh, K. J.; Kaur, Kulwinder; Bhatia, Gaurav

2017-05-01

Magnetically attracted silica coated MnFe2O4 samples have been prepared by using co-precipitation method. Structural changes have been confirmed from XRD spectra. Ferromagnetic behavior of samples has been studied by using vibration sample magnetometer. Cytotoxicity and cell culture of samples have been investigated by using human MG63 cell line and found that sample provide a healthy environment to the growth of cell lines. Drug carrier ability of sample has been checked with gentamycin as an antibiotic and results show that sample can be used as excellent drug carriers. Drug loaded samples can be easily targeted to specific area due to their attractive nature towards external magnetic field. Moreover, magnetic nanoparticles can also be used to kill the cancer cells by using hyperthermia technique. Hyperthermia is a process to raise the temperature of surrounding cells in the presence of external AC magnetic field above the maximum temperature limit for surviving of the cancer cells. Cancer cell can survive only up to 47°C. After that cancer cells start to die, but healthy cells can easily survive up to higher temperature. Our results indicate that prepared samples possess good drug carrier ability and hence, can be potential candidates for cancer cell treatment.

Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

Directory of Open Access Journals (Sweden)

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.

Protein nanoparticles as drug delivery carriers for cancer therapy.

Science.gov (United States)

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.

Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer-90Y conjugates in treatment of prostate tumors

International Nuclear Information System (INIS)

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

Erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy

Science.gov (United States)

Zhu, Dao-Ming; Xie, Wei; Xiao, Yu-Sha; Suo, Meng; Zan, Ming-Hui; Liao, Qing-Quan; Hu, Xue-Jia; Chen, Li-Ben; Chen, Bei; Wu, Wen-Tao; Ji, Li-Wei; Huang, Hui-Ming; Guo, Shi-Shang; Zhao, Xing-Zhong; Liu, Quan-Yan; Liu, Wei

2018-02-01

Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies were used to modify the RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were coated with the modified RBC membranes. These new nanoparticles were termed EpCam-RPAuNs. We characterized the capability of the EpCam-RPAuNs for selective tumor targeting via exposure to near-infrared irradiation. The experimental results demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validated the biocompatibility of the EpCam-RAuNs in vitro. By combining the molecularly modified targeting RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer diagnoses and therapies.

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

International Nuclear Information System (INIS)

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)

Aptamer-modified nanoparticles and their use in cancer diagnostics and treatment.

Science.gov (United States)

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.

Cytotoxic Effect on Cancerous Cell Lines by Biologically Synthesized Silver Nanoparticles

Directory of Open Access Journals (Sweden)

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.

Microwaves for breast cancer treatments

Directory of Open Access Journals (Sweden)

Heba Abdelhamid Elkayal

2015-12-01

Full Text Available Hyperthermia is potentially an effective method for the treatment of cancer, especially breast cancer tumors. One of the most attractive attributes of hyperthermia is the possibility of providing therapeutic benefit noninvasively, minimizing side effects. To be effective, a hyperthermia treatment must selectively heat the cancerous tissue, elevating the temperature in the tumor without exposing healthy tissue to excessive temperature elevations. In this paper, a suggested simple model of Annular Phased Array (APA using eight half wavelength linear dipoles is presented. New software (COMSOL MULTIPHYSICS is used to calculate the temperature distribution inside a model of a three layered breast (skin, breast tissue, and tumor. In addition, the effect of changing the amplitude and phases of the array elements on the temperature distributions and the conditions on the values of the phases are demonstrated in order to achieve the objective of hyperthermia for breast tumor treatment.

Hyaluronic acid-modified zirconium phosphate nanoparticles for potential lung cancer therapy.

Science.gov (United States)

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.

Targeting thyroid cancer with acid-triggered release of doxorubicin from silicon dioxide nanoparticles

Directory of Open Access Journals (Sweden)

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

Amine-modified hyaluronic acid-functionalized porous silicon nanoparticles for targeting breast cancer tumors

Science.gov (United States)

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

Improved magnetic induction heating of nanoferrites for hyperthermia applications: Correlation with colloidal stability and magneto-structural properties

International Nuclear Information System (INIS)

Khot, V.M.; Salunkhe, A.B.; Ruso, J.M.; Pawar, S.H.

2015-01-01

Nanoferrites with compositions Mn 0.4 Zn 0.6 Fe 2 O 4 , Co 0.4 Zn 0.6 Fe 2 O 4 , Ni 0.4 Zn 0.6 Fe 2 O 4 (MZF, CZF and NZF respectively) coated with polyethylene glycol (PEG) were prepared in a single step. These nanoparticles are highly water dispersible with zeta potential values between 14 and 21 mV. Magnetic induction heating characteristics of these NPs have been studied as a function of magnetic field amplitude from 6.7 to 26.7 kA m −1 (at fixed frequency 265 kHz) and concentration of nanoparticles. Notable enhancement in specific absorption rate (334.5 W g −1 ) by CZF nanoparticles has been observed. This enhanced induction heating properties have been studied and correlated with colloidal stability and magnetostructural properties such as tuned magnetic anisotropy arising from zinc substitution. Cytotoxicity of synthesized mixed ferrites has been evaluated in vitro on HeLa cell lines using MTT assay to explore their use as heating agents in magnetic hyperthermia. - Highlights: • Magnetic nanoferrites (sizes 8–12 nm) with improved specific absorption rate (334.5 W g −1 ) at lowest particle concentration have been prepared • The results have been explained by correlating colloidal stability and magnetostructural properties such as magnetocrystalline anisotropy. • It has been shown that substitution of zinc tunes anisotropy of cobalt iron oxide within the value optimized previously in achieving high throughput in magnetic induction heating. • In vitro cytotoxicity proves nanoparticles are non-toxic suggesting their use as a potential heating agent in hyperthermia therapy

New developments in breast cancer therapy: role of iron oxide nanoparticles

Science.gov (United States)

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.

Long duration mild temperature hyperthermia and brachytherapy.

Science.gov (United States)

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.

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

OpenAIRE

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 ...

Emerging applications of nanoparticles for lung cancer diagnosis and therapy

Science.gov (United States)

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.

WE-G-303-04: Intrinsically Radiolabeled Nanoparticles: An Emerging Paradigm

Energy Technology Data Exchange (ETDEWEB)

Cai, W. [University of Wisconsin-Madison (United States)

2015-06-15

Over the last decade, there has been a growing interest in applying nanotechnology to cancer detection, treatment, and treatment monitoring. Advances in nanotechnology have enabled the fabrication of nanoparticles from various materials with different shapes and sizes. Nanoparticles can be accumulated preferentially within tumors by either “passive targeting” through a phenomenon typically known as “enhanced permeability and retention” or “active targeting” in which nanoparticles are conjugated with antibodies or peptides directed against tumor and/or stromal markers. The tumor specificity of nanoparticles in conjunction with their unique physicochemical properties offers many novel strategies for cancer treatment and detection. For example, notable approaches in the radiation oncology setting include the use of gold nanoparticles for radiation response modulation of tumor or normal tissue and thermal ablation or hyperthermia treatment of tumors. Some of these approaches are currently being tested either on humans or on animals and, very likely, will become the clinical reality in the near future. Various computational and experimental techniques have also been applied to address unique research issues associated with nanoparticles and may become the standard tools for future investigations and clinical translations. Therefore, both clinicians and researchers may need to be properly educated about the basic principles as well as the promise of nanoparticle-based applications with regard to the future of cancer diagnostics and therapeutics. This symposium will familiarize the audience with the potential applications of nanoparticles in oncologic imaging and therapy using specific illustrative examples. The audience will be properly oriented by these illustrative examples to the multiple avenues for collaborative research amongst interdisciplinary teams of physicists, clinicians, engineers, chemists, and biologists in industry and academia. Learning

WE-G-303-04: Intrinsically Radiolabeled Nanoparticles: An Emerging Paradigm

International Nuclear Information System (INIS)

Cai, W.

2015-01-01

Over the last decade, there has been a growing interest in applying nanotechnology to cancer detection, treatment, and treatment monitoring. Advances in nanotechnology have enabled the fabrication of nanoparticles from various materials with different shapes and sizes. Nanoparticles can be accumulated preferentially within tumors by either “passive targeting” through a phenomenon typically known as “enhanced permeability and retention” or “active targeting” in which nanoparticles are conjugated with antibodies or peptides directed against tumor and/or stromal markers. The tumor specificity of nanoparticles in conjunction with their unique physicochemical properties offers many novel strategies for cancer treatment and detection. For example, notable approaches in the radiation oncology setting include the use of gold nanoparticles for radiation response modulation of tumor or normal tissue and thermal ablation or hyperthermia treatment of tumors. Some of these approaches are currently being tested either on humans or on animals and, very likely, will become the clinical reality in the near future. Various computational and experimental techniques have also been applied to address unique research issues associated with nanoparticles and may become the standard tools for future investigations and clinical translations. Therefore, both clinicians and researchers may need to be properly educated about the basic principles as well as the promise of nanoparticle-based applications with regard to the future of cancer diagnostics and therapeutics. This symposium will familiarize the audience with the potential applications of nanoparticles in oncologic imaging and therapy using specific illustrative examples. The audience will be properly oriented by these illustrative examples to the multiple avenues for collaborative research amongst interdisciplinary teams of physicists, clinicians, engineers, chemists, and biologists in industry and academia. Learning

A novel hyperthermia treatment for bone metastases using magnetic materials

International Nuclear Information System (INIS)

Matsumine, Akihiko; Asanuma, Kunihiro; Matsubara, Takao; Nakamura, Tomoki; Uchida, Atsumasa; Sudo, Akihiro; Takegami, Kenji

2011-01-01

Patients with bone metastases in the extremities sometimes require surgical intervention to prevent deterioration of quality of life due to a pathological fracture. The use of localized radiotherapy combined with surgical reinforcement has been a gold standard for the treatment of bone metastases. However, radiotherapy sometimes induces soft tissue damage, including muscle induration and joint contracture. Moreover, cancer cells are not always radiosensitive. Hyperthermia has been studied since the 1940s using an experimental animal model to treat various types of advanced cancer, and studies have now reached the stage of clinical application, especially in conjunction with radiotherapy or chemotherapy. Nevertheless, bone metastases have several special properties which discourage oncologists from developing hyperthermic therapeutic strategies. First, the bone is located deep in the body, and has low thermal conductivity due to the thickness of cortical bone and the highly vascularized medulla. To address these issues, we developed new hyperthermic strategies which generate heat using magnetic materials under an alternating electromagnetic field, and started clinical application of this treatment modality. The purpose of this review is to summarize the latest studies on hyperthermic treatment in the field of musculoskeletal tumors, and to introduce the treatment strategy employing our novel hyperthermia approach. (author)

Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo

Directory of Open Access Journals (Sweden)

Li Y

2011-11-01

Full Text Available Yuntao Li1,2, Jing Liu1, Yuejiao Zhong3, Jia Zhang1, Ziyu Wang1, Li Wang1, Yanli An1, Mei Lin1, Zhiqiang Gao2, Dongsheng Zhang11School of Medicine, Southeast University, Nanjing, Jiangsu Province, People's Republic of China; 2Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China; 3Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, Jiangsu Province, People's Republic of ChinaPurpose: This research was conducted to assess the biocompatibility of the core-shell Fe3O4@Au composite magnetic nanoparticles (MNPs, which have potential application in tumor hyperthermia. Methods: Fe3O4@Au composite MNPs with core-shell structure were synthesized by reduction of Au3+ in the presence of Fe3O4-MNPs prepared by improved co-precipitation. Cytotoxicity assay, hemolysis test, micronucleus (MN assay, and detection of acute toxicity in mice and beagle dogs were then carried out.Results: The result of cytotoxicity assay showed that the toxicity grade of this material on mouse fibroblast cell line (L-929 was classified as grade 1, which belongs to no cytotoxicity. Hemolysis rates showed 0.278%, 0.232%, and 0.197%, far less than 5%, after treatment with different concentrations of Fe3O4@Au composite MNPs. In the MN assay, there was no significant difference in MN formation rates between the experimental groups and negative control (P > 0.05, but there was a significant difference between the experimental groups and the positive control (P < 0.05. The median lethal dose of the Fe3O4@Au composite MNPs after intraperitoneal administration in mice was 8.39 g/kg, and the 95% confidence interval was 6.58-10.72 g/kg, suggesting that these nanoparticles have a wide safety margin. Acute toxicity testing in beagle dogs also showed no significant difference in body weight between the treatment groups at 1, 2, 3, and 4 weeks after liver injection and no behavioral changes. Furthermore, blood

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

Science.gov (United States)

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.

Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment

Directory of Open Access Journals (Sweden)

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

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

Science.gov (United States)

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

Polymeric nanoparticles for the intracellular delivery of paclitaxel in lung and breast cancer

Science.gov (United States)

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

Comparison between experimental and predicted specific absorption rate of functionalized iron oxide nanoparticle suspensions

Energy Technology Data Exchange (ETDEWEB)

Yuan Yuan [Mechanical, Aerospace and Nuclear Engineering Department Rensselaer Polytechnic Institute, Troy, NY 12180 (United States); Tasciuc, Diana-Andra Borca, E-mail: borcad@rpi.edu [Mechanical, Aerospace and Nuclear Engineering Department Rensselaer Polytechnic Institute, Troy, NY 12180 (United States)

2011-10-15

Radio-frequency heated magnetic nanoaparticle suspensions have potential applications in cancer hyperthermia. To optimize these systems for hyperthermia applications it is important to be able to predict how their heat generation or specific absorption rate (SAR) is influenced by various factors, including nanoparticle coating or functionalization and aggregation. However, at present it is unclear how well-existing models predict experimental SAR results. Direct comparisons between predicted and measured SAR are scarce, despite an abundance of works reporting on heat generation rate of various magnetic nanoparticles suspensions. The main objective of this paper is to experimentally assess the validity of current models for SAR and extract information on the effects of coating and aggregation on heat generation rate. In this context, AC susceptibility and magnetization of suspensions of uncoated particles, as well as particles with aminosilane and carboxymethyl-dextran functionalizations, were measured. These properties were then used to predict the heat generation rate in alternating magnetic field starting from first principles, which was then compared to measured SAR. It was found that experimental SAR agrees relatively well with predictions (by a factor of two) when using experimental susceptibility values for the SAR calculation. However, for uncoated and amine-functionalized particles poor agreement (more than an order of magnitude difference) was found when the experimental susceptibility was substituted with predictions based on the Debye model. This apparent discrepancy is attributed to dipolar interactions between nanoparticles within aggregates in these samples, which enhances the imaginary part of the susceptibility and, consequently, the SAR values. The results also suggest that the thermal resistance effect of the coating has little influence on the SAR. - Highlights: > Thermal resistance of nanoparticle coating has little impact on heat dissipation

Self-assembled gemcitabine-gadolinium nanoparticles for magnetic resonance imaging and cancer therapy.

Science.gov (United States)

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.

Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain.

Science.gov (United States)

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.

Covalent IR820-PEG-diamine nanoconjugates for theranostic applications in cancer

Directory of Open Access Journals (Sweden)

Fernandez-Fernandez A

2014-10-01

Full Text Available Alicia Fernandez-Fernandez,1,2 Romila Manchanda,1,3 Denny Carvajal,1,4 Tingjun Lei,1,5 Supriya Srinivasan,1 Anthony J McGoron11Biomedical Engineering Department, Florida International University, Miami, FL, USA; 2Physical Therapy Department, Nova Southeastern University, Fort Lauderdale, FL, USA; 3Chemistry Department, Galgotias University, Greater Noida, UP, India; 4Mount Sinai Medical Center, 5Cirle, Miami, FL, USAAbstract: Near-infrared dyes can be used as theranostic agents in cancer management, based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and nonspecific biodistribution. Nanoconjugate formulations of cyanine dyes, such as IR820, may be able to overcome some of these limitations. We covalently conjugated IR820 with 6 kDa polyethylene glycol (PEG-diamine to create a nanoconjugate (IRPDcov with potential for in vivo applications. The conjugation process resulted in nearly spherical, uniformly distributed nanoparticles of approximately 150 nm diameter and zeta potential -0.4±0.3 mV. The IRPDcov formulation retained the ability to fluoresce and to cause hyperthermia-mediated cell-growth inhibition, with enhanced internalization and significantly enhanced cytotoxic hyperthermia effects in cancer cells compared with free dye. Additionally, IRPDcov demonstrated a significantly longer (P<0.05 plasma half-life, elimination half-life, and area under the curve (AUC value compared with IR820, indicating larger overall exposure to the theranostic agent in mice. The IRPDcov conjugate had different organ localization than did free IR820, with potential reduced accumulation in the kidneys and significantly lower (P<0.05 accumulation in the lungs. Some potential advantages of IR820-PEG-diamine nanoconjugates may include passive targeting of tumor tissue through the enhanced permeability and retention effect, prolonged

Hyperthermia

International Nuclear Information System (INIS)

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

Real-time cellular and molecular dynamics of bi-metallic self-therapeutic nanoparticle in cancer cells

Science.gov (United States)

Vishwakarma, Sandeep Kumar; Bardia, Avinash; Lakkireddy, Chandrakala; Paspala, Syed Ameer Basha; Habeeb, Md. Aejaz; Khan, Aleem Ahmed

2018-02-01

Since last decades various kinds of nanoparticles have been functionalized to improve their biomedical applications. However, the biological effect of un-modified/non-functionalized bi-metallic magnetic nanoparticles remains under investigated. Herein we demonstrate a multifaceted non-functionalized bi-metallic inorganic Gd-SPIO nanoparticle which passes dual high MRI contrast and can kill the cancer cells through several mechanisms. The results of the present study demonstrate that Gd-SPIO nanoparticles have potential to induce cancer cell death by production of reactive oxygen species and apoptotic events. Furthermore, Gd-SPIO nanoparticles also enhance the expression levels of miRNA-199a and miRNA-181a-7p which results in decreased levels of cancer markers such as C-met, TGF-β and hURP. One very interesting finding of this study reveals side scatter-based real-time analysis of nanoparticle uptake in cancer cells using flow cytometry analysis. In conclusion, this study paves a way for future investigation of un-modified inorganic nanoparticles to purport enhanced therapeutic effect in combination with potential anti-tumor drugs/molecules in cancer cells.

Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles

Energy Technology Data Exchange (ETDEWEB)

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.

Preferential killing of cancer cells and activated human T cells using ZnO nanoparticles

International Nuclear Information System (INIS)

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

Field-dependent dynamic responses from dilute magnetic nanoparticle dispersions

DEFF Research Database (Denmark)

Fock, Jeppe; Balceris, Christoph; Costo, Rocio

2018-01-01

The response of magnetic nanoparticles (MNPs) to an oscillating magnetic field outside the linear response region is important for several applications including magnetic hyperthermia, magnetic resonance imaging and biodetection. The size and magnetic moment are two critical parameters for the pe...

Hyperthermia: clinical results

International Nuclear Information System (INIS)

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

Hyperthermia and radiotherapy

International Nuclear Information System (INIS)

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

WE-G-303-03: Advances in in Vivo Magnetic NanoparticleSensing

Energy Technology Data Exchange (ETDEWEB)

Weaver, J. [Dartmouth-Hitchcock Medical Center (United States)

2015-06-15

Over the last decade, there has been a growing interest in applying nanotechnology to cancer detection, treatment, and treatment monitoring. Advances in nanotechnology have enabled the fabrication of nanoparticles from various materials with different shapes and sizes. Nanoparticles can be accumulated preferentially within tumors by either “passive targeting” through a phenomenon typically known as “enhanced permeability and retention” or “active targeting” in which nanoparticles are conjugated with antibodies or peptides directed against tumor and/or stromal markers. The tumor specificity of nanoparticles in conjunction with their unique physicochemical properties offers many novel strategies for cancer treatment and detection. For example, notable approaches in the radiation oncology setting include the use of gold nanoparticles for radiation response modulation of tumor or normal tissue and thermal ablation or hyperthermia treatment of tumors. Some of these approaches are currently being tested either on humans or on animals and, very likely, will become the clinical reality in the near future. Various computational and experimental techniques have also been applied to address unique research issues associated with nanoparticles and may become the standard tools for future investigations and clinical translations. Therefore, both clinicians and researchers may need to be properly educated about the basic principles as well as the promise of nanoparticle-based applications with regard to the future of cancer diagnostics and therapeutics. This symposium will familiarize the audience with the potential applications of nanoparticles in oncologic imaging and therapy using specific illustrative examples. The audience will be properly oriented by these illustrative examples to the multiple avenues for collaborative research amongst interdisciplinary teams of physicists, clinicians, engineers, chemists, and biologists in industry and academia. Learning

WE-G-303-03: Advances in in Vivo Magnetic NanoparticleSensing

International Nuclear Information System (INIS)

Weaver, J.

2015-01-01

Over the last decade, there has been a growing interest in applying nanotechnology to cancer detection, treatment, and treatment monitoring. Advances in nanotechnology have enabled the fabrication of nanoparticles from various materials with different shapes and sizes. Nanoparticles can be accumulated preferentially within tumors by either “passive targeting” through a phenomenon typically known as “enhanced permeability and retention” or “active targeting” in which nanoparticles are conjugated with antibodies or peptides directed against tumor and/or stromal markers. The tumor specificity of nanoparticles in conjunction with their unique physicochemical properties offers many novel strategies for cancer treatment and detection. For example, notable approaches in the radiation oncology setting include the use of gold nanoparticles for radiation response modulation of tumor or normal tissue and thermal ablation or hyperthermia treatment of tumors. Some of these approaches are currently being tested either on humans or on animals and, very likely, will become the clinical reality in the near future. Various computational and experimental techniques have also been applied to address unique research issues associated with nanoparticles and may become the standard tools for future investigations and clinical translations. Therefore, both clinicians and researchers may need to be properly educated about the basic principles as well as the promise of nanoparticle-based applications with regard to the future of cancer diagnostics and therapeutics. This symposium will familiarize the audience with the potential applications of nanoparticles in oncologic imaging and therapy using specific illustrative examples. The audience will be properly oriented by these illustrative examples to the multiple avenues for collaborative research amongst interdisciplinary teams of physicists, clinicians, engineers, chemists, and biologists in industry and academia. Learning

Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

International Nuclear Information System (INIS)

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

Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

Energy Technology Data Exchange (ETDEWEB)

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.

Preparation of manganese-based perovskite nanoparticles using a ...

Indian Academy of Sciences (India)

In addition, the heating ability of the LSMTO nanoparticles was evaluated under a safe alternating magnetic field used in magnetic hyperthermia therapy. The results showed the fast magneto-temperature response of the prepared samplewith sufficient heat loss at the therapeutic temperature range, indicating the LSMTO ...

Multilayered Magnetic Nanoparticles Fabricated by Nanoimprint Lithography for Magnetomechanical Treatment of Cancer

Science.gov (United States)

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

Hyperthermia: Clinical promise and current challenges

International Nuclear Information System (INIS)

Kapp, D.S.

1987-01-01

Local-regional hyperthermia (HT) when used in conjunction with radiation therapy (XRT), has been shown in numerous clinical trials to result in considerable improvement in response rates and local tumor control rates when compared with treatment by XRT alone. Although considerable progress has been made in understanding the biological basis for hyperthermia induced cytotoxicity and radiosensitization, additional research remains in establishing the optimal treatment schedules for the clinical utilization of HT-XRT. The number of HT treatments; the sequencing of HT and XRT; the frequency of administration of HT; and the ideal temperature-time parameters all remain to be better defined for the clinical setting. The role of tumor blood flow on the thermal distributions also warrants further investigation. In addition, considerable effort is needed to improve hyperthermia equipment in order to provide more uniform therapeutic temperature distributions (temperatures ≥42.5%C). Better heating equipment is particularly needed for the treatment of deep seeted tumors. Pertinent clinical literature will be presented summarizing the clinical promise of hyperthermia and the above mentioned clinical challenges

Improved magnetic induction heating of nanoferrites for hyperthermia applications: Correlation with colloidal stability and magneto-structural properties

Energy Technology Data Exchange (ETDEWEB)

Khot, V.M., E-mail: wish_khot@yahoo.co.in [Center for Interdisciplinary Research, D. Y. Patil University, Kolhapur 416006 (India); Salunkhe, A.B. [Advanced Materials Laboratory, Department of Physics, Savitribai Phule University of Pune (India); Ruso, J.M. [Soft Matter and Molecular Biophysics Group, Applied Physics Department, University of Santiago de Compostela, Santiago de Compostela (Spain); Pawar, S.H. [Center for Interdisciplinary Research, D. Y. Patil University, Kolhapur 416006 (India)

2015-06-15

Nanoferrites with compositions Mn{sub 0.4}Zn{sub 0.6}Fe{sub 2}O{sub 4}, Co{sub 0.4}Zn{sub 0.6}Fe{sub 2}O{sub 4}, Ni{sub 0.4}Zn{sub 0.6}Fe{sub 2}O{sub 4} (MZF, CZF and NZF respectively) coated with polyethylene glycol (PEG) were prepared in a single step. These nanoparticles are highly water dispersible with zeta potential values between 14 and 21 mV. Magnetic induction heating characteristics of these NPs have been studied as a function of magnetic field amplitude from 6.7 to 26.7 kA m{sup −1} (at fixed frequency 265 kHz) and concentration of nanoparticles. Notable enhancement in specific absorption rate (334.5 W g{sup −1}) by CZF nanoparticles has been observed. This enhanced induction heating properties have been studied and correlated with colloidal stability and magnetostructural properties such as tuned magnetic anisotropy arising from zinc substitution. Cytotoxicity of synthesized mixed ferrites has been evaluated in vitro on HeLa cell lines using MTT assay to explore their use as heating agents in magnetic hyperthermia. - Highlights: • Magnetic nanoferrites (sizes 8–12 nm) with improved specific absorption rate (334.5 W g{sup −1}) at lowest particle concentration have been prepared • The results have been explained by correlating colloidal stability and magnetostructural properties such as magnetocrystalline anisotropy. • It has been shown that substitution of zinc tunes anisotropy of cobalt iron oxide within the value optimized previously in achieving high throughput in magnetic induction heating. • In vitro cytotoxicity proves nanoparticles are non-toxic suggesting their use as a potential heating agent in hyperthermia therapy.

Role of regional radiofrequency hyperthermia after hepatic artery block in the normal pit liver

International Nuclear Information System (INIS)

Luo Jingwei; Xu Guozhen; Xiong Jinghong; Liu Xiaoyun; Wang Weihu; Li Yexiong

2003-01-01

Objective: To study the temperature difference, tolerated high temperature, pathological changes between normal and blocked hepatic artery in radiofrequency hyperthermia for pig liver. Methods: Mature pig was used with iodine blocked right hepatic artery. Heat of the whole liver was given for 1 hour by SR-1000 radiofrequency hyperthermia with four thermocouple probes to measure the temperature of the right hepatic artery, right and left normal liver and rectum. Results: Temperature of blocked right liver increased by 10.2 degree C from 39.1 degree C to 49.3 degree C as compared with the left liver of which the temperature rose by 6.8 degree C from 39.7 degree C to 46.5 degree C but the temperature of right hepatic artery and rectum rose only by 3.3 degree C, 3.2 degree C respectively. After sacrificing the pig one week later, on lobe exploration, severe necrosis was observed in the right lobe but the left lobe was normal with a clear demarcation between the two lobes. Conclusions: Hepatic arterial iodine embolization potentiates radiofrequency hyperthermia in the liver. Liver with blocked artery showed conspicuous necrosis but liver with normal un-blocked artery was able to tolerate 46.5 degree C. This provides some evidence for the combination of regional hyperthermia and hepatic artery block in the treatment of advanced liver cancer

Magnetic, structural and magnetocaloric properties of Ni-Si and Ni-Al thermoseeds for self-controlled hyperthermia.

Science.gov (United States)

Pandey, Sudip; Quetz, Abdiel; Aryal, Anil; Dubenko, Igor; Mazumdar, Dipanjan; Stadler, Shane; Ali, Naushad

2017-11-01

Self-controlled hyperthermia is a non-invasive technique used to kill or destroy cancer cells while preserving normal surrounding tissues. We have explored bulk magnetic Ni-Si and Ni-Al alloys as a potential thermoseeds. The structural, magnetic and magnetocaloric properties of the samples were investigated, including saturation magnetisation, Curie temperature (T C ), and magnetic and thermal hysteresis, using room temperature X-ray diffraction and magnetometry. The annealing time, temperature and the effects of homogenising the thermoseeds were studied to determine the functional hyperthermia applications. The bulk Ni-Si and Ni-Al binary alloys have Curie temperatures in the desired range, 316 K-319 K (43 °C-46 °C), which is suitable for magnetic hyperthermia applications. We have found that T C strictly follows a linear trend with doping concentration over a wide range of temperature. The magnetic ordering temperature and the magnetic properties can be controlled through substitution in these binary alloys.

Neuronal Rat Brain Damage Caused by Endogenous and Exogenous Hyperthermia

Directory of Open Access Journals (Sweden)

Mustafa Aydın

2012-03-01

Full Text Available OBJECTIVE: Hyperthermia may induce pathologic alterations within body systems and organs including brain. In this study, neuronal effects of endogenous and exogenous hyperthermia (41°C were studied in rats. METHODS: The endogenous hyperthermia (41°C was induced by lipopolysaccharide and the exogenous by an (electric heater. Possible neuronal damage was evaluated by examining healthy, apoptotic and necrotic cells, and heat shock proteins (HSP 27, HSP 70 in the cerebral cortex, cerebellum and hypothalamus RESULTS: At cellular level, when all neuronal tissues are taken into account; (i a significant increase in the necrotic cells was observed in the both groups (p0.05. CONCLUSION: The neural tissue of brain can show different degree of response to hyperthermia. But we can conclude that endogenous hyperthermia is more harmful to central nervous system than exogenous hyperthermia

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

Science.gov (United States)

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

Magnetic nanoparticle design for medical application

Czech Academy of Sciences Publication Activity Database

Mornet, S.; Vasseur, S.; Grasset, F.; Veverka, Pavel; Goglio, G.; Demourgues, A.; Portier, J.; Pollert, Emil; Duguet, E.

2006-01-01

Roč. 34, - (2006), s. 237-247 ISSN 0079-6786 R&D Projects: GA AV ČR(CZ) 1QS100100553; GA AV ČR(CZ) KAN200200651 Institutional research plan: CEZ:AV0Z10100521 Keywords : magnetic nanoparticles * medical applications * magnetic resonance imaging * magnetic hyperthermia Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 2.500, year: 2006

Regional hyperthermia of the liver

International Nuclear Information System (INIS)

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)

On the improvement of regional hyperthermia treatment

NARCIS (Netherlands)

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

SU-F-J-05: The Effect of Air Pockets in the Urinary Bladder During Bladder Hyperthermia Treatment

Energy Technology Data Exchange (ETDEWEB)

Schooneveldt, G.; Kok, H.P.; Bakker, A.; Geijsen, E.D.; Reijke, T.M. de; Crezee, J. [Academisch Medisch Centrum / Universiteit van Amsterdam, Amsterdam (Netherlands)

2016-06-15

Purpose: Hyperthermia combined with Mitomycin C is used for the treatment of non-muscle invasive bladder cancer (NMIBC), using a phased array system of microwave antennas for bladder heating. Often some air is present in the bladder, which effectively blocks the microwave radiation, potentially preventing proper treatment of that part of the bladder. Air can be a relevant fraction of the bladder content and large air pockets are expected to have a noticeable influence on achieved temperatures. Methods: We analysed 14 NMIBC patients treated at our institute with our AMC-4 hyperthermia device with four 70MHz antennas around the pelvis. A CT scan was made after treatment and a physician delineated the bladder on the CT scan. On the same scan, the amount of air present in the bladder was delineated. Using our in-house developed hyperthermia treatment planning system, we simulated the treatment using the clinically applied device settings. We did this once with the air pocket delineated on the CT scan, and once with the same volume filled with bladder tissue. Results: The patients had on average 4.2ml (range 0.8–10.1ml) air in the bladder. The bladder volume was delineated by the physician, that is including air pocket and bladder wall, was on average 253ml (range 93–452ml). The average volume in which changes exceeded 0.25°C was 22ml (range 0–108 ml), with the bladder being up to 2°C cooler when an air pocket was present. Except for extreme cases, there was no evident relation between the quantity of air and the difference in temperature. Conclusion: The effect of an air pocket in the bladder during bladder hyperthermia treatment varies strongly between patients. Generally, this leads to lower temperatures in the bladder, potentially affecting treatment quality, and suggesting that care need be taken to minimise the size of air pockets during hyperthermia treatments. The KWF Dutch Cancer Society financially supported this work, grant UVA 2012-5539.

ADPRT inhibitors and hyperthermia as radiosensitizers

International Nuclear Information System (INIS)

Jonsson, G.G.

1985-01-01

Hyperthermia given in combination with gamma radiation has given considerable improvement in the therapeutic results for treatment of malignant tumors. The mechanism behind the hyperthermia effect is probably operative at the tissue level as well as at the molecular level. The metabolism of NAD + in relation to the activity of the chromosomal enzyme ADP-ribosyl transferase (ADPRT) has been studied as a possible molecular mechanism for this effect. The ADPRT activity was measured after radiosensitization with both hyperthermia and nicotinamide, which is a potent inhibitor of ADPRT. The results indicate that hyperthermia can improve the effect of radiotherapy by reducing the supply of NAD + , which is a co-substrate for ADPRT, while nicotinamide functions as a radiosensitizing agent by direct inhibition of the enzyme. The hypothesis is discussed in the thesis where inhibition of ADPRT might increase the radiosensitivity because the radiation-induced DNA damage can not be repaired with normal efficiency. The function of nicotinamide as a radiosensitizer was verified by studies on C3H mice with transplanted spontaneous mammary tumors. Because nicotinamide is not toxic, it seems quite attractive to test this vitamin as a radiosensitizing agent against human tumors. (251 refs.) (author)

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

Directory of Open Access Journals (Sweden)

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.

A multicenter study of using carbon nanoparticles to show sentinel lymph nodes in early gastric cancer.

Science.gov (United States)

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.

Nanoparticle-based photodynamic therapy on non-melanoma skin cancer

Science.gov (United States)

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.

Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

International Nuclear Information System (INIS)

Badylak, S.F.; Babbs, C.F.

1984-01-01

The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 0 C and 45 0 for 20 minutes) were studied by light and electron microscopy. Normal muscle and Walker 256 tumors showed vascular damage at 5 minutes post-heating (PH), followed by suppuration and thrombosis at 6 and 48 hours PH, and by regeneration and repair at 7 days PH. Endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive ischemic injury occurred for at least 48 hours PH. Two hyperthermia treatments, separated by a 30 or 60 minute cooling interval, were applied to rats implanted with Walker 256 tumors. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results characterized the sequential morphologic alterations following hyperthermia treatment and showed that: 1) vascular damage contributed to the immediate and latent cytotoxic effects of hyperthermia, 2) selective heating occurred in the neoplastic tissue disrupted by prior heat treatment, and 3) not all neoplasms are responsive to hyperthermia treatment

Ultra-high sensitivity imaging of cancer using SERRS nanoparticles

Science.gov (United States)

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.

Nanoparticles of Selaginella doederleinii leaf extract inhibit human lung cancer cells A549

Science.gov (United States)

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.

Dual-Mode Imaging-Guided Synergistic Chemo- and Magnetohyperthermia Therapy in a Versatile Nanoplatform To Eliminate Cancer Stem Cells.

Science.gov (United States)

Tang, Jinglong; Zhou, Huige; Liu, Jiaming; Liu, Jing; Li, Wanqi; Wang, Yuqing; Hu, Fan; Huo, Qing; Li, Jiayang; Liu, Ying; Chen, Chunying

2017-07-19

Cancer stem cells (CSCs) have been identified as a new target for therapy in diverse cancers. Traditional therapies usually kill the bulk of cancer cells, but are often unable to effectively eliminate CSCs, which may lead to drug resistance and cancer relapse. Herein, we propose a novel strategy: fabricating multifunctional magnetic Fe 3 O 4 @PPr@HA hybrid nanoparticles and loading it with the Notch signaling pathway inhibitor N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycinet-butylester (DAPT) to eliminate CSCs. Hyaluronic acid ligands greatly enhance the accumulation of the hybrid nanoparticles in the tumor site and in the CSCs. Both hyaluronase in the tumor microenvironment and the magnetic hyperthermia effect of the inner magnetic core can accelerate the release of DAPT. This controlled release of DAPT in the tumor site further enhances the ability of the combination of chemo- and magnetohyperthermia therapy to eliminate cancer stem cells. With the help of polypyrrole-mediated photoacoustic and Fe 3 O 4 -mediated magnetic resonance imaging, the drug release can be precisely monitored in vivo. This versatile nanoplatform enables effective elimination of the cancer stem cells and monitoring of the drugs.

Biocompatibility of magnetic Fe3O4 nanoparticles and their cytotoxic effect on MCF-7 cells

Directory of Open Access Journals (Sweden)

Chen DZ

2012-09-01

Full Text Available Daozhen Chen,1,3,* Qiusha Tang,2,* Xiangdong Li,3,* Xiaojin Zhou,1 Jia Zang,1 Wen-qun Xue,1 Jing-ying Xiang,1 Cai-qin Guo11Central Laboratory, Wuxi Hospital for Matemaland Child Health Care Affiliated Medical School of Nanjing, Jiangsu Province; 2Department of Pathology and Pathophysiology, Medical College, Southeast University, Jiangsu Province; 3The People’s Hospital of Aheqi County, Xinjiang, China *These authors contributed equally to this workBackground: The objective of this study was to evaluate the synthesis and biocompatibility of Fe3O4 nanoparticles and investigate their therapeutic effects when combined with magnetic fluid hyperthermia on cultured MCF-7 cancer cells.Methods: Magnetic Fe3O4 nanoparticles were prepared using a coprecipitation method. The appearance, structure, phase composition, functional groups, surface charge, magnetic susceptibility, and release in vitro were characterized by transmission electron microscopy, x-ray diffraction, scanning electron microscopy-energy dispersive x-ray spectroscopy, and a vibrating sample magnetometer. Blood toxicity, in vitro toxicity, and genotoxicity were investigated. Therapeutic effects were evaluated by MTT [3-(4, 5-dimethyl-2-thiazolyl-2, 5-diphenyl-2H-tetrazolium bromide] and flow cytometry assays.Results: Transmission electron microscopy revealed that the shapes of the Fe3O4 nanoparticles were approximately spherical, with diameters of about 26.1 ± 5.2 nm. Only the spinel phase was indicated in a comparison of the x-ray diffraction data with Joint Corporation of Powder Diffraction Standards (JCPDS X-ray powder diffraction files. The O-to-Fe ratio of the Fe3O4 was determined by scanning electron microscopy-energy dispersive x-ray spectroscopy elemental analysis, and approximated pure Fe3O4. The vibrating sample magnetometer hysteresis loop suggested that the Fe3O4 nanoparticles were superparamagnetic at room temperature. MTT experiments showed that the toxicity of the material

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

Science.gov (United States)

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.

Magnetic fluid hyperthermia probed by both calorimetric and dynamic hysteresis measurements

Science.gov (United States)

Guibert, Clément; Fresnais, Jérôme; Peyre, Véronique; Dupuis, Vincent

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.

Infrared fibers for radiometer thermometry in hypothermia and hyperthermia treatment

International Nuclear Information System (INIS)

Katzir, A.; Bowman, H.F.; Asfour, Y.; Zur, A.; Valeri, C.R.

1989-01-01

Hypothermia is a condition which results from prolonged exposure to a cold environment. Rapid and efficient heating is needed to rewarm the patient from 32-35 degrees C to normal body temperature. Hyperthermia in cancer treatment involves heating malignant tumors to 42.5-43.0 degrees C for an extended period (e.g., 30 min) in an attempt to obtain remission. Microwave or radio frequency heating is often used for rewarming in hypothermia or for temperature elevation in hyperthermia treatment. One severe problem with such heating is the accurate measurement and control of temperature in the presence of a strong electromagnetic field. For this purpose, we have developed a fiberoptic radiometer system which is based on a nonmetallic, infrared fiber probe, which can operate either in contact or noncontact mode. In preliminary investigations, the radiometer worked well in a strong microwave or radiofrequency field, with an accuracy of +/- 0.5 degrees C. This fiberoptic thermometer was used to control the surface temperature of objects within +/- 2 degrees C

Cooperative nanomaterials systems for cancer diagnosis and therapeutics

Science.gov (United States)

Park, Ji Ho

The unique electromagnetic and biologic properties of nanomaterials are being harnessed to build powerful new medical technologies. Particularly, there have been recently increasing interests in cancer nanotechnology, wherein nanomaterials play an important role in ultrasensitive imaging, targeting, and therapy of cancer. However, these nanomaterials typically function as individual units and are designed to independently perform their tasks. In this dissertation, new cooperative nanosystems consisting of two distinct nanomaterials that work together to target, identify, or treat tumors in vivo were studied. In the first two chapters, the synthesis of worm-shaped dextran-coated iron oxide nanoparticles (nanoworms, NW) exhibiting substantial in vivo circulation times and significant tumor targeting when coated with tumor-homing peptides were studied. NWs are also found to display a greater magnetic resonance (MR) response than the spherical nanoparticles. Next, two types of multifunctional nanoparticles were fabricated for simultaneous detection and treatment of cancer. Micellar hybrid nanoparticles (MHN) that contain magnetic nanoparticles, quantum dots, and an anti-cancer drug doxorubicin (DOX) within a single PEG-modified phospholipid micelle were first prepared. Simultaneous multimodal imaging (MR and fluorescence) and targeted drug delivery in vitro and in vivo was performed using DOX-incorporated targeted MHN. Secondly, luminescent porous silicon nanoparticles (LPSINP) that were drug-loadable, biodegradable and relatively non-toxic were prepared. In contrast to most inorganic nanomaterials, LPSINP were degraded in vivo in a relatively short time with no noticeable toxicity. The clearance and degradation of intravenously injected LPSINP in the bladder, liver, and spleen were established by whole-body fluorescence imaging. Finally, two types of cooperative nanomaterials systems to amplify targeting and deliver drugs efficiently to regions of tumor invasion were

Multimodal doxorubicin loaded magnetic nanoparticles for VEGF targeted theranostics of breast cancer.

Science.gov (United States)

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.

Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

Science.gov (United States)

Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing; Ware, Matthew J; Law, Justin J; Newton, Jared M; Nguyen, Lam; Curley, Steven A; Corr, Stuart J

2018-04-02

Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Improving immunological tumor microenvironment using electro-hyperthermia followed by dendritic cell immunotherapy.

Science.gov (United States)

Tsang, Yuk-Wah; Huang, Cheng-Chung; Yang, Kai-Lin; Chi, Mau-Shin; Chiang, Hsin-Chien; Wang, Yu-Shan; Andocs, Gabor; Szasz, Andras; Li, Wen-Tyng; Chi, Kwan-Hwa

2015-10-15

The treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs. The CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied. mEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity. This study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy.

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

Directory of Open Access Journals (Sweden)

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.

Composite magnetic nanoparticles: Synthesis and cancer-related applications

International Nuclear Information System (INIS)

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)

NON-INVASIVE RADIOFREQUENCY ABLATION OF CANCER TARGETED BY GOLD NANOPARTICLES

Science.gov (United States)

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

Nanotechnology and cancer: improving real-time monitoring and staging of bladder cancer with multimodal mesoporous silica nanoparticles.

Science.gov (United States)

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

Dual drug loaded chitosan nanoparticles-sugar--coated arsenal against pancreatic cancer.

Science.gov (United States)

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.

Immunogenicity of ascites tumor cells following in vitro hyperthermia

International Nuclear Information System (INIS)

Dickson, J.A.; Jasiewicz, M.L.; Simpson, A.C.

1982-01-01

The concept that host immunization may be achieved by heat-induced antigenic modifications of cancer cells and/or the release of immunogenic products by dead or dying tumor cells following in vitro heating was examined. Ehrlich ascites cells were used, inasmuch as it was claimed that in vitro hyperthermia increased the immunogenicity of these cells. Tumor cell populations of different viability were obtained by heating Ehrlich cells at 42.5 degrees, 45 degrees, or 60 degrees C. Viable and nonviable cells were separated by Ficoll-Hypaque density centrifugation; viable nonreplicating cells were obtained by treatment with mitomycin C. Cell populations of different viability after heating were left to die slowly over 3 days at 37 degrees C. Swiss TO mice were then given injections of the treated cells and/or medium. No survival benefit occurred in mice inoculated with any of these different components and then challenged with viable tumor cells. Injection of irradiated cells, however, did produce host immunity. Similarly, D23 rat hepatoma ascites cells produced host immunity after 15,000 rad but not after heating. The claim that in vitro hyperthermia increases the immunogenicity of tumor cells was not confirmed

Cancer cell-selective promoter recognition accompanies antitumor effect by glucocorticoid receptor-targeted gold nanoparticle

Science.gov (United States)

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

Studies on Preparation of Photosensitizer Loaded Magnetic Silica Nanoparticles and Their Anti-Tumor Effects for Targeting Photodynamic Therapy

Directory of Open Access Journals (Sweden)

Chen Zhi-Long

2009-01-01

Full Text Available Abstract As a fast developing alternative of traditional therapeutics, photodynamic therapy (PDT is an effective, noninvasive, nontoxic therapeutics for cancer, senile macular degeneration, and so on. But the efficacy of PDT was compromised by insufficient selectivity and low solubility. In this study, novel multifunctional silica-based magnetic nanoparticles (SMNPs were strategically designed and prepared as targeting drug delivery system to achieve higher specificity and better solubility. 2,7,12,18-Tetramethyl-3,8-di-(1-propoxyethyl-13,17-bis-(3-hydroxypropyl porphyrin, shorted as PHPP, was used as photosensitizer, which was first synthesized by our lab with good PDT effects. Magnetite nanoparticles (Fe3O4 and PHPP were incorporated into silica nanoparticles by microemulsion and sol–gel methods. The prepared nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and fluorescence spectroscopy. The nanoparticles were approximately spherical with 20–30 nm diameter. Intense fluorescence of PHPP was monitored in the cytoplasm of SW480 cells. The nanoparticles possessed good biocompatibility and could generate singlet oxygen to cause remarkable photodynamic anti-tumor effects. These suggested that PHPP-SMNPs had great potential as effective drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy.

Magnetic hyperthermia of laponite based ferrofluid

Energy Technology Data Exchange (ETDEWEB)

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.

Safety and efficacy of targeted hyperthermia treatment utilizing gold nanorod therapy in spontaneous canine neoplasia.

Science.gov (United States)

Schuh, Elizabeth M; Portela, Roberta; Gardner, Heather L; Schoen, Christian; London, Cheryl A

2017-10-02

Hyperthermia is an established anti-cancer treatment but is limited by tolerance of adjacent normal tissues. Parenteral administration of gold nanorods (NRs) as a photosensitizer amplifies the effects of hyperthermia treatment while sparing normal tissues. This therapy is well tolerated and has demonstrated anti-tumor effects in mouse models. The purpose of this phase 1 study was to establish the safety and observe the anti-tumor impact of gold NR enhanced (plasmonic) photothermal therapy (PPTT) in client owned canine patients diagnosed with spontaneous neoplasia. Seven dogs underwent gold NR administration and subsequent NIR PPTT. Side effects were mild and limited to local reactions to NIR laser. All of the dogs enrolled in the study experienced stable disease, partial remission or complete remission. The overall response rate (ORR) was 28.6% with partial or complete remission of tumors at study end. PPTT utilizing gold nanorod therapy can be safely administered to canine patients. Further studies are needed to determine the true efficacy in a larger population of canine cancer patients and to and identify those patients most likely to benefit from this therapy.

Best Practices in Cancer Nanotechnology – Perspective from NCI Nanotechnology Alliance

Science.gov (United States)

Zamboni, William C.; Torchilin, Vladimir; Patri, Anil; Hrkach, Jeff; Stern, Stephen; Lee, Robert; Nel, Andre; Panaro, Nicholas J.; Grodzinski, Piotr

2014-01-01

Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities which are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems which could not be effectively solved in the past and include overcoming formulation issues, multi-drug-resistance phenomenon and penetrating cellular barriers that may limit device accessibility to intended targets such as the blood-brain-barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise towards new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics. PMID:22669131

Designing nanoconjugates to effectively target pancreatic cancer cells in vitro and in vivo.

Directory of Open Access Journals (Sweden)

Jameel Ahmad Khan

Full Text Available Pancreatic cancer is the fourth leading cause of cancer related deaths in America. Monoclonal antibodies are a viable treatment option for inhibiting cancer growth. Tumor specific drug delivery could be achieved utilizing these monoclonal antibodies as targeting agents. This type of designer therapeutic is evolving and with the use of gold nanoparticles it is a promising approach to selectively deliver chemotherapeutics to malignant cells. Gold nanoparticles (GNPs are showing extreme promise in current medicinal research. GNPs have been shown to non-invasively kill tumor cells by hyperthermia using radiofrequency. They have also been implemented as early detection agents due to their unique X-ray contrast properties; success was revealed with clear delineation of blood capillaries in a preclinical model by CT (computer tomography. The fundamental parameters for intelligent design of nanoconjugates are on the forefront. The goal of this study is to define the necessary design parameters to successfully target pancreatic cancer cells.The nanoconjugates described in this study were characterized with various physico-chemical techniques. We demonstrate that the number of cetuximab molecules (targeting agent on a GNP, the hydrodynamic size of the nanoconjugates, available reactive surface area and the ability of the nanoconjugates to sequester EGFR (epidermal growth factor receptor, all play critical roles in effectively targeting tumor cells in vitro and in vivo in an orthotopic model of pancreatic cancer.Our results suggest the specific targeting of tumor cells depends on a number of crucial components 1 targeting agent to nanoparticle ratio 2 availability of reactive surface area on the nanoparticle 3 ability of the nanoconjugate to bind the target and 4 hydrodynamic diameter of the nanoconjugate. We believe this study will help define the design parameters for formulating better strategies for specifically targeting tumors with nanoparticle

Nanoparticle mediated ablation of breast cancer cells using a nanosecond pulsed electric field

Science.gov (United States)

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.

CD44-engineered mesoporous silica nanoparticles for overcoming multidrug resistance in breast cancer

International Nuclear Information System (INIS)

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

Polymer–lipid hybrid anti-HER2 nanoparticles for targeted salinomycin delivery to HER2-positive breast cancer stem cells and cancer cells

Directory of Open Access Journals (Sweden)

Li J

2017-09-01

Full Text Available Jun Li,1,* Wenqing Xu,2,* Xiaoli Yuan,3,* Huaiwen Chen,3 Hao Song,1,4 Bingquan Wang,5 Jun Han5 1College of Pharmacy, Liaocheng University, Liaocheng, Shandong, 2Railway Police College, Zhengzhou, 3Department of Cadre Health Care, Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu, 4Centre for Stem Cell & Regenerative Medicine, Liaocheng People’s Hospital, 5Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng, Shandong, China *These authors contributed equally to this work Purpose: Breast cancer stem cells (CSCs are responsible for the initiation, recurrence, and metastasis of breast cancer. Sufficient evidence has established that breast cancer cells can spontaneously turn into breast CSCs. Thus, it is essential to simultaneously target breast CSCs and cancer cells to maximize the efficacy of breast cancer therapy. HER2 has been found to be overexpressed in both breast CSCs and cancer cells. We developed salinomycin-loaded polymer–lipid hybrid anti-HER2 nanoparticles (Sali-NP-HER2 to target both HER2-positive breast CSCs and cancer cells.Methods: The antitumor activity of Sali-NP-HER2 constructed by conjugating anti-HER2 antibodies to polymer–lipid salinomycin nanoparticles was evaluated in vitro and in vivo.Results: Sali-NP-HER2 efficiently bound to HER2-positive breast CSCs and cancer cells, resulting in enhanced cytotoxic effects compared with non-targeted nanoparticles or salinomycin. In mice bearing breast cancer xenografts, administration of Sali-NP-HER2 exhibited superior efficacy in inhibiting tumor growth. Sali-NP-HER2 reduced the breast tumorsphere formation rate and the proportion of breast CSCs more effectively than non-targeted nanoparticles or salinomycin alone.Conclusion: Sali-NP-HER2 represents a promising approach in treating HER2-positive breast cancer by targeting both breast CSCs and cancer cells. Keywords: nanoparticles, breast cancer, cancer stem cells, salinomycin, HER2

The Role of Dextran Coatings on the Cytotoxicity Properties of Ceria Nanoparticles Toward Bone Cancer Cells

Science.gov (United States)

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.

Correlation of structural and magnetic properties of Fe{sub 3}O{sub 4} nanoparticles with their calorimetric and magnetorheological performance

Energy Technology Data Exchange (ETDEWEB)

Sedlacik, M.; Moucka, R.; Kozakova, Z. [Centre of Polymer Systems, University Institute, Tomas Bata University in Zlin, Nad Ovcirnou 3685, 760 01 Zlin (Czech Republic); Polymer Centre, Faculty of Technology, Tomas Bata University in Zlin, namesti T.G. Masaryka 275, 762 72 Zlin (Czech Republic); Kazantseva, N.E., E-mail: nekazan@yahoo.com [Centre of Polymer Systems, University Institute, Tomas Bata University in Zlin, Nad Ovcirnou 3685, 760 01 Zlin (Czech Republic); Polymer Centre, Faculty of Technology, Tomas Bata University in Zlin, namesti T.G. Masaryka 275, 762 72 Zlin (Czech Republic); Pavlinek, V.; Kuritka, I. [Centre of Polymer Systems, University Institute, Tomas Bata University in Zlin, Nad Ovcirnou 3685, 760 01 Zlin (Czech Republic); Polymer Centre, Faculty of Technology, Tomas Bata University in Zlin, namesti T.G. Masaryka 275, 762 72 Zlin (Czech Republic); Kaman, O. [Institute of Physics, AS CR, v.v.i., Cukrovarnicka 10/112, 162 53, Prague 6 (Czech Republic); Peer, P. [Institute of Hydrodynamics, AS CR, v.v.i., Pod Patankou 5, 166 12, Prague 6 (Czech Republic)

2013-01-15

Magnetic particles based on Fe{sub 3}O{sub 4} were prepared by means of the microwave solvothermal method under different reaction conditions with the intention of their utilization as a mediator in magnetic hyperthermia and material for reducing blood flow in the tumor area. The synthesized particles were characterized in terms of their structure, size, shape, and magnetic properties with an emphasis on the correlation between particle morphology and magnetic properties. Most importantly, their heat development when exposed to an alternating magnetic field was determined, as well as the rheological behavior of their suspensions under static magnetic field. Reasonable heat development and substantial flow resistance under the effect of magnetic field indicate their potential for applications such as hyperthermia mediators or substances for temporary embolization. - Highlights: Black-Right-Pointing-Pointer Fe{sub 3}O{sub 4} nanoparticles were obtained by microwave-assisted synthesis Black-Right-Pointing-Pointer Nucleation agents affect morphological and magnetic properties of nanoparticles. Black-Right-Pointing-Pointer Aqueous ammonia nucleated Fe{sub 3}O{sub 4} nanoparticles show high heating ability in AC magnetic field due to Neel relaxation. Black-Right-Pointing-Pointer Suspension of Fe{sub 3}O{sub 4} in silicone oil demonstrates flow resistance under DC magnetic field caused by chain formation. Black-Right-Pointing-Pointer Fe{sub 3}O{sub 4} nanoparticles has potential as a hyperthermia mediator and substance for temporary embolization.

Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure

Energy Technology Data Exchange (ETDEWEB)

Kukielka, A.M.; Hetnal, M.; Dabrowski, T.; Walasek, T.; Brandys, P.; Reinfuss, M. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Radiotherapy, Krakow (Poland); Nahajowski, D.; Kudzia, R.; Dybek, D. [Centre of Oncology, M. Sklodowska - Curie Institute, Krakow Branch, Department of Medical Physics, Department of Radiotherapy, Krakow (Poland)

2014-02-15

The aim of the present retrospective study is to evaluate toxicity and early clinical outcomes of interstitial hyperthermia (IHT) combined with high-dose rate (HDR) brachytherapy as a salvage treatment in patients with biopsy-confirmed local recurrence of prostate cancer after previous external beam radiotherapy. Between September 2008 and March 2013, 25 patients with local recurrence of previously irradiated prostate cancer were treated. The main eligibility criteria for salvage prostate HDR brachytherapy combined with interstitial hyperthermia were biopsy confirmed local recurrence and absence of nodal and distant metastases. All patients were treated with a dose of 30 Gy in 3 fractions at 21-day intervals. We performed 62 hyperthermia procedures out of 75 planned (83 %). The aim of the hyperthermia treatment was to heat the prostate to 41-43 C for 60 min. Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03). Determination of subsequent biochemical failure was based on the Phoenix definition (nadir + 2 ng/ml). The median age was 71 years (range 62-83 years), the median initial PSA level was 16.3 ng/ml (range 6.37-64 ng/ml), and the median salvage PSA level was 2.8 ng/ml (1.044-25.346 ng/ml). The median follow-up was 13 months (range 4-48 months). The combination of HDR brachytherapy and IHT was well tolerated. The most frequent complications were nocturia, weak urine stream, urinary frequency, hematuria, and urgency. Grade 2 rectal hemorrhage was observed in 1 patient. No grade 3 or higher complications were observed. The 2-year Kaplan-Meier estimate of biochemical control after salvage treatment was 74 %. The PSA in 20 patients decreased below the presalvage level, while 11 patients achieved a PSA nadir < 0.5 ng/ml. All patients are still alive. Of the 7 patients who experienced biochemical failure, bone metastases were found in 2 patients. IHT in combination

Radiofrequency hyperthermia for advanced malignant liver tumors

International Nuclear Information System (INIS)

Nagata, Y.; Okuno, Y.; Mitsumori, M.; Akuta, K.; Nishimura, Y.; Masunaga, S.; Kanamori, S.; Fujishiro, M.; Hiraoka, M.; Takahashi, M.; Abe, M.

1996-01-01

Purpose: To evaluate thermometry and the clinical results of radiofrequency (RF) thermotherapy for advanced malignant liver tumors. Materials and Methods One-hundred and seventy-three patients with malignant liver tumors treated between 1983 and 1995 underwent hyperthermia. Surgery were contraindicated in all patients. The 173 tumors consisted of 114 hepatocellular carcinomas(HCCs), and 59 non-HCCs(45 metastatic liver tumors and 12 cholangiocarcinomas). Eight MHz RF capacitive heating equipment was used for hyperthermia. Two opposing 25-cm or 30-cm electrodes were generally used for heating liver tumors. Our standard protocol was to administer hyperthermia 40-50 minutes twice a week to a total of 8 sessions. Temperature of the liver tumor was measured by microthermocouples. In each patient, a single catheter was inserted into the liver tumor through the normal liver. Transcatheter arterial embolization, radiotherapy, immunotherapy, and chemotherapy were combined with hyperthermia depending on the patient's liver function and tumor location. The therapeutic efficacy was evaluated by the change in tumor size assessed by computed tomography (CT) three or four months after the completion of treatment. Results One-hundred and forty (81%) of 173 patients underwent hyperthermia more than 4 times. Thermometry could be performed in 77(55%) of these 140 patients. Neither systolic nor diastolic blood pressure changed significantly after hyperthermia. However, pulse rate significantly increased from 82.8 ± 1.1 to 96.5 ± 1.3 beats/min. Only 21 patients (11%) showed a decrease in pulse rate after hyperthermia. Body temperature increased from 36.3 ±0.1 to 37.4±0.2 after hyperthermia. Sequelae of hyperthermia included focal fat burning in 20 (12%), gastric ulceration in 4 (2%), and liver necrosis in 1(1%). Sequelae of thermometry were severe peritoneal pain in 7 (11%), intraperitoneal hematoma in 1(1%), and pneumothorax in one (1%) patient. The maximal tumor temperature

A Novel Docetaxel-Loaded Poly (ɛ-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

Science.gov (United States)

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.

Hybrid Organic-Inorganic Bridged Silsesquioxane Nanoparticles for Cancer Nanomedicine

KAUST Repository

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

Hybrid Organic-Inorganic Bridged Silsesquioxane Nanoparticles for Cancer Nanomedicine

KAUST Repository

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

Interstitial microwave hyperthermia treatment investigations

International Nuclear Information System (INIS)

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.

Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls

Science.gov (United States)

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

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

International Nuclear Information System (INIS)

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.

Nanoparticle "Theranostic" Platforms for Applications in Cancer

Science.gov (United States)

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

Recent progress in biomedical applications of magnetic nanoparticles

KAUST Repository

Giouroudi, Ioanna

2010-06-01

Magnetic nanoparticles have been proposed for biomedical applications for several years. Various research groups worldwide have focused on improving their synthesis, their characterization techniques and the specific tailoring of their properties. Yet, it is the recent, impressive advances in nanotechnology and biotechnology which caused the breakthrough in their successful application in biomedicine. This paper aims at reviewing some current biomedical applications of magnetic nanoparticles as well as some recent patents in this field. Special emphasis is placed on i) hyperthermia, ii) therapeutics iii) diagnostics. Future prospects are also discussed. © 2010 Bentham Science Publishers Ltd.

Investigation of temperature dependent magnetic hyperthermia in Fe3O4 ferrofluids

Science.gov (United States)

Nemala, Humeshkar Bhaskar