Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe

Directory of Open Access Journals (Sweden)

Ying Chen

2017-08-01

Full Text Available Redox imbalance in cells induces lipid peroxidation and generates a class of highly reactive metabolites known as lipid-derived electrophiles (LDEs that can modify proteins and affects their functions. Identifying targets of LDEs is critical to understand how such modifications are functionally implicated in oxidative-stress associated diseases. Here we report a quantitative chemoproteomic method to globally profile protein targets and sites modified by LDEs. In this strategy, we designed and synthesized an alkyne-functionalized aminooxy probe to react with LDE-modified proteins for imaging and proteomic profiling. Using this probe, we successfully quantified >4000 proteins modified by 4-hydroxy-2-nonenal (HNE of high confidence in mammalian cell lysate and combined with a tandem-orthogonal proteolysis activity-based protein profiling (TOP-ABPP strategy, we identified ~400 residue sites targeted by HNE including reactive cysteines in peroxiredoxins, an important family of enzymes with anti-oxidant roles. Our method expands the toolbox to quantitatively profile protein targets of endogenous electrophiles and the enlarged inventory of LDE-modified proteins and sites will contribute to functional elucidation of cellular pathways affected by oxidative stress. Keywords: Lipid-derived electrophile, 4-hydroxy-2-nonenal, Chemoproteomics, Aminooxy probe, Activity-based protein profiling

Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake

International Nuclear Information System (INIS)

Parab, Harshala J; Huang, Jing-Hong; Liu, Ru-Shi; Lai, Tsung-Ching; Jan, Yi-Hua; Wang, Jui-Ling; Hsiao, Michael; Chen, Chung-Hsuan; Hwu, Yeu-Kuang; Tsai, Din Ping; Chuang, Shih-Yi; Pang, Jong-Hwei S

2011-01-01

The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface modification of Au-HMP nanoparticles was carried out using polyethylene glycol and transferrin to produce molecular probes for possible clinical applications. In vitro cell viability studies performed using as-synthesized Au-HMP nanoparticles and their surface-modified counterparts reveal the biocompatibility of the nanoparticles. The transferrin-conjugated nanoparticles have significantly higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral mucosa fibroblast cells), as determined by inductively coupled plasma mass spectrometry. This study demonstrates the possibility of using an inexpensive and non-toxic food additive, HMP, as a stabilizer in the large-scale generation of biocompatible and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake

Energy Technology Data Exchange (ETDEWEB)

Parab, Harshala J; Huang, Jing-Hong; Liu, Ru-Shi [Department of Chemistry, National Taiwan University, Taipei 106, Taiwan (China); Lai, Tsung-Ching; Jan, Yi-Hua; Wang, Jui-Ling; Hsiao, Michael; Chen, Chung-Hsuan [Genomics Research Center, Academia Sinica, Taipei 115, Taiwan (China); Hwu, Yeu-Kuang [Institute of Physics, Academia Sinica, Taipei 115, Taiwan (China); Tsai, Din Ping [Department of Physics, National Taiwan University, Taipei 106, Taiwan (China); Chuang, Shih-Yi; Pang, Jong-Hwei S, E-mail: rsliu@ntu.edu.tw, E-mail: mhsiao@gate.sinica.edu.tw [Graduate Institute of Clinical Medical Sciences, Chang Gung University, Tao-Yuan, Taiwan (China)

2011-09-30

The feasibility of using gold nanoparticles (AuNPs) for biomedical applications has led to considerable interest in the development of novel synthetic protocols and surface modification strategies for AuNPs to produce biocompatible molecular probes. This investigation is, to our knowledge, the first to elucidate the synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface modification of Au-HMP nanoparticles was carried out using polyethylene glycol and transferrin to produce molecular probes for possible clinical applications. In vitro cell viability studies performed using as-synthesized Au-HMP nanoparticles and their surface-modified counterparts reveal the biocompatibility of the nanoparticles. The transferrin-conjugated nanoparticles have significantly higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral mucosa fibroblast cells), as determined by inductively coupled plasma mass spectrometry. This study demonstrates the possibility of using an inexpensive and non-toxic food additive, HMP, as a stabilizer in the large-scale generation of biocompatible and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

Family- and genus-level 16S rRNA-targeted oligonucleotide probes for ecological studies of methanotrophic bacteria.

Science.gov (United States)

Gulledge, J; Ahmad, A; Steudler, P A; Pomerantz, W J; Cavanaugh, C M

2001-10-01

Methanotrophic bacteria play a major role in the global carbon cycle, degrade xenobiotic pollutants, and have the potential for a variety of biotechnological applications. To facilitate ecological studies of these important organisms, we developed a suite of oligonucleotide probes for quantitative analysis of methanotroph-specific 16S rRNA from environmental samples. Two probes target methanotrophs in the family Methylocystaceae (type II methanotrophs) as a group. No oligonucleotide signatures that distinguish between the two genera in this family, Methylocystis and Methylosinus, were identified. Two other probes target, as a single group, a majority of the known methanotrophs belonging to the family Methylococcaceae (type I/X methanotrophs). The remaining probes target members of individual genera of the Methylococcaceae, including Methylobacter, Methylomonas, Methylomicrobium, Methylococcus, and Methylocaldum. One of the family-level probes also covers all methanotrophic endosymbionts of marine mollusks for which 16S rRNA sequences have been published. The two known species of the newly described genus Methylosarcina gen. nov. are covered by a probe that otherwise targets only members of the closely related genus Methylomicrobium. None of the probes covers strains of the newly proposed genera Methylocella and "Methylothermus," which are polyphyletic with respect to the recognized methanotrophic families. Empirically determined midpoint dissociation temperatures were 49 to 57 degrees C for all probes. In dot blot screening against RNA from positive- and negative-control strains, the probes were specific to their intended targets. The broad coverage and high degree of specificity of this new suite of probes will provide more detailed, quantitative information about the community structure of methanotrophs in environmental samples than was previously available.

Multifunctional gadolinium-based dendritic macromolecules as liver targeting imaging probes.

Science.gov (United States)

Luo, Kui; Liu, Gang; He, Bin; Wu, Yao; Gong, Qingyong; Song, Bin; Ai, Hua; Gu, Zhongwei

2011-04-01

The quest for highly efficient and safe contrast agents has become the key factor for successful application of magnetic resonance imaging (MRI). The gadolinium (Gd) based dendritic macromolecules, with precise and tunable nanoscopic sizes, are excellent candidates as multivalent MRI probes. In this paper, a novel series of Gd-based multifunctional peptide dendritic probes (generation 2, 3, and 4) possessing highly controlled structures and single molecular weight were designed and prepared as liver MRI probes. These macromolecular Gd-ligand agents exhibited up to 3-fold increase in T(1) relaxivity comparing to Gd-DTPA complexes. No obvious in vitro cytotoxicity was observed from the measured concentrations. These dendritic probes were further functionalized with multiple galactosyl moieties and led to much higher cell uptake in vitro as demonstrated in T(1)-weighted scans. During in vivo animal studies, the probes provided better signal intensity (SI) enhancement in mouse liver, especially at 60 min post-injection, with the most efficient enhancement from the galactosyl moiety decorated third generation dendrimer. The imaging results were verified with analysis of Gd content in liver tissues. The design strategy of multifunctional Gd-ligand peptide dendritic macromolecules in this study may be used for developing other sensitive MRI probes with targeting capability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Targeted Capture and High-Throughput Sequencing Using Molecular Inversion Probes (MIPs).

Science.gov (United States)

Cantsilieris, Stuart; Stessman, Holly A; Shendure, Jay; Eichler, Evan E

2017-01-01

Molecular inversion probes (MIPs) in combination with massively parallel DNA sequencing represent a versatile, yet economical tool for targeted sequencing of genomic DNA. Several thousand genomic targets can be selectively captured using long oligonucleotides containing unique targeting arms and universal linkers. The ability to append sequencing adaptors and sample-specific barcodes allows large-scale pooling and subsequent high-throughput sequencing at relatively low cost per sample. Here, we describe a "wet bench" protocol detailing the capture and subsequent sequencing of >2000 genomic targets from 192 samples, representative of a single lane on the Illumina HiSeq 2000 platform.

Investigations of ultrafast charge dynamics in laser-irradiated targets by a self probing technique employing laser driven protons

Energy Technology Data Exchange (ETDEWEB)

Ahmed, H. [School of Mathematics and Physics, Queen' s University Belfast, BT7 1NN (United Kingdom); Kar, S., E-mail: s.kar@qub.ac.uk [School of Mathematics and Physics, Queen' s University Belfast, BT7 1NN (United Kingdom); Cantono, G. [School of Mathematics and Physics, Queen' s University Belfast, BT7 1NN (United Kingdom); Department of Physics “E. Fermi”, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Consiglio Nazionale delle Ricerche, Istituto Nazionale di Ottica, Research Unit Adriano Gozzini, via G. Moruzzi 1, Pisa 56124 (Italy); Nersisyan, G. [School of Mathematics and Physics, Queen' s University Belfast, BT7 1NN (United Kingdom); Brauckmann, S. [Institut für Laser-und Plasmaphysik, Heinrich-Heine-Universität, Düsseldorf (Germany); Doria, D.; Gwynne, D. [School of Mathematics and Physics, Queen' s University Belfast, BT7 1NN (United Kingdom); Macchi, A. [Department of Physics “E. Fermi”, Largo B. Pontecorvo 3, 56127 Pisa (Italy); Consiglio Nazionale delle Ricerche, Istituto Nazionale di Ottica, Research Unit Adriano Gozzini, via G. Moruzzi 1, Pisa 56124 (Italy); Naughton, K. [School of Mathematics and Physics, Queen' s University Belfast, BT7 1NN (United Kingdom); Willi, O. [Institut für Laser-und Plasmaphysik, Heinrich-Heine-Universität, Düsseldorf (Germany); Lewis, C.L.S.; Borghesi, M. [School of Mathematics and Physics, Queen' s University Belfast, BT7 1NN (United Kingdom)

2016-09-01

The divergent and broadband proton beams produced by the target normal sheath acceleration mechanism provide the unique opportunity to probe, in a point-projection imaging scheme, the dynamics of the transient electric and magnetic fields produced during laser-plasma interactions. Commonly such experimental setup entails two intense laser beams, where the interaction produced by one beam is probed with the protons produced by the second. We present here experimental studies of the ultra-fast charge dynamics along a wire connected to laser irradiated target carried out by employing a ‘self’ proton probing arrangement – i.e. by connecting the wire to the target generating the probe protons. The experimental data shows that an electromagnetic pulse carrying a significant amount of charge is launched along the wire, which travels as a unified pulse of 10s of ps duration with a velocity close to speed of light. The experimental capabilities and the analysis procedure of this specific type of proton probing technique are discussed. - Highlights: • Prompt charging of laser irradiated target generates ultra-short EM pulses. • Its ultrafast propagation along a wire was studied by self-proton probing technique. • Self-proton probing technique is the proton probing with one laser pulse. • Pulse temporal profile and speed along the wire were measured with high resolution.

Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology.

Science.gov (United States)

Galdeano, Carles; Ciulli, Alessio

2016-09-01

Targeting epigenetic proteins is a rapidly growing area for medicinal chemistry and drug discovery. Recent years have seen an explosion of interest in developing small molecules binding to bromodomains, the readers of acetyl-lysine modifications. A plethora of co-crystal structures has motivated focused fragment-based design and optimization programs within both industry and academia. These efforts have yielded several compounds entering the clinic, and many more are increasingly being used as chemical probes to interrogate bromodomain biology. High selectivity of chemical probes is necessary to ensure biological activity is due to an on-target effect. Here, we review the state-of-the-art of bromodomain-targeting compounds, focusing on the structural basis for their on-target selectivity or lack thereof. We also highlight chemical biology approaches to enhance on-target selectivity.

Detection of Pathogenic Biofilms with Bacterial Amyloid Targeting Fluorescent Probe, CDy11

DEFF Research Database (Denmark)

Kim, Jun Young; Sahu, Srikanta; Yau, Yin Hoe

2016-01-01

Bacterial biofilms are responsible for a wide range of persistent infections. In the clinic, diagnosis of biofilm-associated infections relies heavily on culturing methods, which fail to detect nonculturable bacteria. Identification of novel fluorescent probes for biofilm imaging will greatly...... facilitate diagnosis of pathogenic bacterial infection. Herein, we report a novel fluorescent probe, CDy11 (compound of designation yellow 11), which targets amyloid in the Pseudomonas aeruginosa biofilm matrix through a diversity oriented fluorescent library approach (DOFLA). CDy11 was further demonstrated...

The performance of a fiber optic displacement sensor for different types of probes and targets

International Nuclear Information System (INIS)

Yasin, M; Harun, S W; Abdul-Rashid, H A; Kusminarto; Karyono; Ahmad, H

2008-01-01

A simple fiber optic displacement sensor is presented using a multimode plastic bundled fiber and the intensity modulation technique. The performance of the sensor is compared for different types of probes and targets. The probe with the largest receiving core diameter demonstrates the highest linearity range, and increasing the number of receiving cores increases the sensitivity of the sensor. With a stainless steel target and the concentric bundled fiber with 16 receiving fibers as a probe, the sensitivity of the sensor is found to be 0.0220 mV/μm over 150 to 550 μm range and – 0.0061 mV/μm over 1100 to 2000 μm range. The target with a higher reflectivity shows a higher sensitivity. The linearity range for the front slope is almost similar for all targets tested. However, for the back slope, lower reflectivity objects have a relatively higher linearity range with the highest range of 1600 μm being obtained using plastic and aluminum targets. The simplicity of the design, high degree of sensitivity, dynamic range, non-contact measurement and low cost of the fabrication make it suitable for applications in industries for position control and micro displacement measurement in the hazardous regions

Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer

DEFF Research Database (Denmark)

Sun, Yao; Ma, Xiaowei; Zhang, Zhe

2016-01-01

Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high...

UPAR targeted molecular imaging of cancers with small molecule-based probes.

Science.gov (United States)

Ding, Feng; Chen, Seng; Zhang, Wanshu; Tu, Yufeng; Sun, Yao

2017-10-15

Molecular imaging can allow the non-invasive characterization and measurement of biological and biochemical processes at the molecular and cellular levels in living subjects. The imaging of specific molecular targets that are associated with cancers could allow for the earlier diagnosis and better treatment of diseases. Small molecule-based probes play prominent roles in biomedical research and have high clinical translation ability. Here, with an emphasis on small molecule-based probes, we review some recent developments in biomarkers, imaging techniques and multimodal imaging in molecular imaging and highlight the successful applications for molecular imaging of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transforming a Targeted Porphyrin Theranostic Agent into a PET Imaging Probe for Cancer

Directory of Open Access Journals (Sweden)

Jiyun Shi, Tracy W.B. Liu, Juan Chen, David Green, David Jaffray, Brian C. Wilson, Fan Wang, Gang Zheng

2011-01-01

Full Text Available Porphyrin based photosensitizers are useful agents for photodynamic therapy (PDT and fluorescence imaging of cancer. Porphyrins are also excellent metal chelators forming highly stable metallo-complexes making them efficient delivery vehicles for radioisotopes. Here we investigated the possibility of incorporating 64Cu into a porphyrin-peptide-folate (PPF probe developed previously as folate receptor (FR targeted fluorescent/PDT agent, and evaluated the potential of turning the resulting 64Cu-PPF into a positron emission tomography (PET probe for cancer imaging. Noninvasive PET imaging followed by radioassay evaluated the tumor accumulation, pharmacokinetics and biodistribution of 64Cu-PPF. 64Cu-PPF uptake in FR-positive tumors was visible on small-animal PET images with high tumor-to-muscle ratio (8.88 ± 3.60 observed after 24 h. Competitive blocking studies confirmed the FR-mediated tracer uptake by the tumor. The ease of efficient 64Cu-radiolabeling of PPF while retaining its favorable biodistribution, pharmacokinetics and selective tumor uptake, provides a robust strategy to transform tumor-targeted porphyrin-based photosensitizers into PET imaging probes.

A high brightness probe of polymer nanoparticles for biological imaging

Science.gov (United States)

Zhou, Sirong; Zhu, Jiarong; Li, Yaping; Feng, Liheng

2018-03-01

Conjugated polymer nanoparticles (CPNs) with high brightness in long wavelength region were prepared by the nano-precipitation method. Based on fluorescence resonance energy transfer (FRET) mechanism, the high brightness property of the CPNs was realized by four different emission polymers. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) displayed that the CPNs possessed a spherical structure and an average diameter of 75 nm. Analysis assays showed that the CPNs had excellent biocompatibility, good photostability and low cytotoxicity. The CPNs were bio-modified with a cell penetrating peptide (Tat, a targeted element) through covalent link. Based on the entire wave fluorescence emission, the functionalized CPNs1-4 can meet multichannel and high throughput assays in cell and organ imaging. The contribution of the work lies in not only providing a new way to obtain a high brightness imaging probe in long wavelength region, but also using targeted cell and organ imaging.

Resveratrol-Loaded Albumin Nanoparticles with Prolonged Blood Circulation and Improved Biocompatibility for Highly Effective Targeted Pancreatic Tumor Therapy

Science.gov (United States)

Geng, Tao; Zhao, Xia; Ma, Meng; Zhu, Gang; Yin, Ling

2017-06-01

Human serum albumin (HSA) is an intrinsic protein and important carrier that transports endogenous as well as exogenous substances across cell membranes. Herein, we have designed and prepared resveratrol (RV)-loaded HSA nanoparticles conjugating RGD (arginine-glycine-aspartate) via a polyethylene glycol (PEG) "bridge" (HRP-RGD NPs) for highly effective targeted pancreatic tumor therapy. HRP-RGD NPs possess an average size of 120 ± 2.6 nm with a narrow distribution, a homodisperse spherical shape, a RV encapsulation efficiency of 62.5 ± 4.21%, and a maximum RV release ratio of 58.4.2 ± 2.8% at pH 5.0 and 37 °C. In vitro biocompatibility of RV is improved after coating with HSA and PEG. Confocal fluorescence images show that HRP-RGD NPs have the highest cellular uptake ratio of 47.3 ± 4.6% compared to HRP NPs and HRP-RGD NPs with free RGD blocking, attributing to an RGD-mediated effect. A cell counting kit-8 (CCK-8) assay indicates that HRP-RGD NPs without RV (HP-RGD NPs) have nearly no cytotoxicity, but HRP-RGD NPs are significantly more cytotoxic to PANC-1 cells compared to free RV and HRP NPs in a concentration dependent manner, showing apoptotic morphology. Furthermore, with a formulated PEG and HSA coating, HRP-RGD NPs prolong the blood circulation of RV, increasing approximately 5.43-fold (t1/2). After intravenous injection into tumor-bearing mice, the content of HRP-RGD NPs in tumor tissue was proven to be approximately 3.01- and 8.1-fold higher than that of HRP NPs and free RV, respectively. Based on these results, HRP-RGD NPs were used in an in vivo anti-cancer study and demonstrated the best tumor growth suppression effect of all tested drugs with no relapse, high in vivo biocompatibility, and no significant systemic toxicity over 35 days treatment. These results demonstrate that HRP-RGD NPs with prolonged blood circulation and improved biocompatibility have high anti-cancer effects with promising future applications in cancer therapy.

Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

International Nuclear Information System (INIS)

Joshi, Bishnu P.; Wang, Thomas D.

2010-01-01

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research

‘Green’-synthesized near-infrared PbS quantum dots with silica-PEG dual-layer coating: ultrastable and biocompatible optical probes for in vivo animal imaging

Science.gov (United States)

Wang, D.; Qian, J.; Cai, F.; He, S.; Han, S.; Mu, Y.

2012-06-01

In this paper, PbS semiconductor quantum dots (QDs) with near-infrared (NIR) photoluminescence were synthesized in oleic acid and paraffin liquid mixture by using an easily handled and ‘green’ approach. Surface functionalization of the QDs was accomplished with a silica and polyethylene glycol (PEG) phospholipid dual-layer coating and the excellent chemical stability of the nanoparticles is demonstrated. We then successfully applied the ultrastable PbS QDs to in vivo sentinel lymph node (SLN) mapping of mice. Histological analyses were also carried out to ensure that the intravenously injected nanoparticles did not produce any toxicity to the organism of mice. These experimental results suggested that our ultrastable NIR PbS QDs can serve as biocompatible and efficient probes for in vivo optical bioimaging and has great potentials for disease diagnosis and clinical therapies in the future.

‘Green’-synthesized near-infrared PbS quantum dots with silica–PEG dual-layer coating: ultrastable and biocompatible optical probes for in vivo animal imaging

International Nuclear Information System (INIS)

Wang, D; Qian, J; Cai, F; He, S; Han, S; Mu, Y

2012-01-01

In this paper, PbS semiconductor quantum dots (QDs) with near-infrared (NIR) photoluminescence were synthesized in oleic acid and paraffin liquid mixture by using an easily handled and ‘green’ approach. Surface functionalization of the QDs was accomplished with a silica and polyethylene glycol (PEG) phospholipid dual-layer coating and the excellent chemical stability of the nanoparticles is demonstrated. We then successfully applied the ultrastable PbS QDs to in vivo sentinel lymph node (SLN) mapping of mice. Histological analyses were also carried out to ensure that the intravenously injected nanoparticles did not produce any toxicity to the organism of mice. These experimental results suggested that our ultrastable NIR PbS QDs can serve as biocompatible and efficient probes for in vivo optical bioimaging and has great potentials for disease diagnosis and clinical therapies in the future. (paper)

Multiple-Targeted Graphene-based Nanocarrier for Intracellular Imaging of mRNAs

Energy Technology Data Exchange (ETDEWEB)

Wang, Ying; Li, Zhaohui; Liu, Misha; Hu, Dehong; Lin, Yuehe; Li, Jinghong

2017-08-29

Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labeled single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis.

PNA-COMBO-FISH: From combinatorial probe design in silico to vitality compatible, specific labelling of gene targets in cell nuclei

Energy Technology Data Exchange (ETDEWEB)

Müller, Patrick; Rößler, Jens; Schwarz-Finsterle, Jutta [University of Heidelberg, Kirchhoff Institute for Physics, Im Neuenheimer Feld 227, D-69120 Heidelberg (Germany); Schmitt, Eberhard, E-mail: eschmitt@kip.uni-heidelberg.de [University of Heidelberg, Kirchhoff Institute for Physics, Im Neuenheimer Feld 227, D-69120 Heidelberg (Germany); University of Göttingen, Institute for Numerical and Applied Mathematics, Lotzestraße 16-18, D-37083 Göttingen (Germany); Hausmann, Michael, E-mail: hausmann@kip.uni-heidelberg.de [University of Heidelberg, Kirchhoff Institute for Physics, Im Neuenheimer Feld 227, D-69120 Heidelberg (Germany)

2016-07-01

Recently, advantages concerning targeting specificity of PCR constructed oligonucleotide FISH probes in contrast to established FISH probes, e.g. BAC clones, have been demonstrated. These techniques, however, are still using labelling protocols with DNA denaturing steps applying harsh heat treatment with or without further denaturing chemical agents. COMBO-FISH (COMBinatorial Oligonucleotide FISH) allows the design of specific oligonucleotide probe combinations in silico. Thus, being independent from primer libraries or PCR laboratory conditions, the probe sequences extracted by computer sequence data base search can also be synthesized as single stranded PNA-probes (Peptide Nucleic Acid probes). Gene targets can be specifically labelled with at least about 20 PNA-probes obtaining visibly background free specimens. By using appropriately designed triplex forming oligonucleotides, the denaturing procedures can completely be omitted. These results reveal a significant step towards oligonucleotide-FISH maintaining the 3D-nanostructure and even the viability of the cell target. The method is demonstrated with the detection of Her2/neu and GRB7 genes, which are indicators in breast cancer diagnosis and therapy. - Highlights: • Denaturation free protocols preserve 3D architecture of chromosomes and nuclei. • Labelling sets are determined in silico for duplex and triplex binding. • Probes are produced chemically with freely chosen backbones and base variants. • Peptide nucleic acid backbones reduce hindering charge interactions. • Intercalating side chains stabilize binding of short oligonucleotides.

PNA-COMBO-FISH: From combinatorial probe design in silico to vitality compatible, specific labelling of gene targets in cell nuclei

International Nuclear Information System (INIS)

Müller, Patrick; Rößler, Jens; Schwarz-Finsterle, Jutta; Schmitt, Eberhard; Hausmann, Michael

2016-01-01

Recently, advantages concerning targeting specificity of PCR constructed oligonucleotide FISH probes in contrast to established FISH probes, e.g. BAC clones, have been demonstrated. These techniques, however, are still using labelling protocols with DNA denaturing steps applying harsh heat treatment with or without further denaturing chemical agents. COMBO-FISH (COMBinatorial Oligonucleotide FISH) allows the design of specific oligonucleotide probe combinations in silico. Thus, being independent from primer libraries or PCR laboratory conditions, the probe sequences extracted by computer sequence data base search can also be synthesized as single stranded PNA-probes (Peptide Nucleic Acid probes). Gene targets can be specifically labelled with at least about 20 PNA-probes obtaining visibly background free specimens. By using appropriately designed triplex forming oligonucleotides, the denaturing procedures can completely be omitted. These results reveal a significant step towards oligonucleotide-FISH maintaining the 3D-nanostructure and even the viability of the cell target. The method is demonstrated with the detection of Her2/neu and GRB7 genes, which are indicators in breast cancer diagnosis and therapy. - Highlights: • Denaturation free protocols preserve 3D architecture of chromosomes and nuclei. • Labelling sets are determined in silico for duplex and triplex binding. • Probes are produced chemically with freely chosen backbones and base variants. • Peptide nucleic acid backbones reduce hindering charge interactions. • Intercalating side chains stabilize binding of short oligonucleotides.

Development of biocompatible and VEGF-targeted paclitaxel nanodrugs on albumin and graphene oxide dual-carrier for photothermal-triggered drug delivery in vitro and in vivo.

Science.gov (United States)

Deng, Wentao; Qiu, Juhui; Wang, Shaoting; Yuan, Zhi; Jia, Yuefeng; Tan, Hailin; Lu, Jiru; Zheng, Ruqiang

2018-01-01

In this study, we performed the characterization and synthesis of biocompatible and targeted albumin and graphene oxide (GO) dual-carrier paclitaxel (PTX) nanoparticles for photothermal-triggered tumor therapy. PTX absorbed on GO nanosheets as cores were coated with human serum albumin (HSA), following surface conjugation with monoclonal antibodies (mAb) against vascular endothelial growth factor (VEGF; denoted as mAbVEGF) via polyethylene glycol linker to form targeted nanoparticles (PTX-GHP-VEGF). The spherical nanoparticles were 191±5 nm in size with good stability and biocompatibility. GO functioned as the first carrier and a near infrared absorber that can generate photothermal effects under 5-minute 808-nm laser irradiation to thermal trigger the release of PTX from the second carrier HSA nanoparticles. The mechanism of thermal-triggered drug release was also investigated preliminarily, in which the heat generated by GO induced swelling of PTX-GHP-VEGF nanoparticles which released the drugs. In vitro studies found that PTX-GHP-VEGF can efficiently target human SW-13 adrenocortical carcinoma cells as evaluated by confocal fluorescence microscopy as well as transmission electron microscopy, and showed an obvious thermal-triggered antitumor effect, mediated by apoptosis. Moreover, PTX-GHP-VEGF combined with near infrared irradiation showed specific tumor suppression effects with high survival rate after 100 days of treatment. PTX-GHP-VEGF also demonstrated high biosafety with no adverse effects on normal tissues and organs. These results highlight the remarkable potential of PTX-GHP-VEGF in photothermal controllable tumor treatment.

Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

Science.gov (United States)

Qin, Zhengtao

Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and

Detection of short repeated genomic sequences on metaphase chromosomes using padlock probes and target primed rolling circle DNA synthesis

Directory of Open Access Journals (Sweden)

Stougaard Magnus

2007-11-01

Full Text Available Abstract Background In situ detection of short sequence elements in genomic DNA requires short probes with high molecular resolution and powerful specific signal amplification. Padlock probes can differentiate single base variations. Ligated padlock probes can be amplified in situ by rolling circle DNA synthesis and detected by fluorescence microscopy, thus enhancing PRINS type reactions, where localized DNA synthesis reports on the position of hybridization targets, to potentially reveal the binding of single oligonucleotide-size probe molecules. Such a system has been presented for the detection of mitochondrial DNA in fixed cells, whereas attempts to apply rolling circle detection to metaphase chromosomes have previously failed, according to the literature. Methods Synchronized cultured cells were fixed with methanol/acetic acid to prepare chromosome spreads in teflon-coated diagnostic well-slides. Apart from the slide format and the chromosome spreading everything was done essentially according to standard protocols. Hybridization targets were detected in situ with padlock probes, which were ligated and amplified using target primed rolling circle DNA synthesis, and detected by fluorescence labeling. Results An optimized protocol for the spreading of condensed metaphase chromosomes in teflon-coated diagnostic well-slides was developed. Applying this protocol we generated specimens for target primed rolling circle DNA synthesis of padlock probes recognizing a 40 nucleotide sequence in the male specific repetitive satellite I sequence (DYZ1 on the Y-chromosome and a 32 nucleotide sequence in the repetitive kringle IV domain in the apolipoprotein(a gene positioned on the long arm of chromosome 6. These targets were detected with good efficiency, but the efficiency on other target sites was unsatisfactory. Conclusion Our aim was to test the applicability of the method used on mitochondrial DNA to the analysis of nuclear genomes, in particular as

NeuroMEMS: Neural Probe Microtechnologies

Directory of Open Access Journals (Sweden)

Sam Musallam

2008-10-01

Full Text Available Neural probe technologies have already had a significant positive effect on our understanding of the brain by revealing the functioning of networks of biological neurons. Probes are implanted in different areas of the brain to record and/or stimulate specific sites in the brain. Neural probes are currently used in many clinical settings for diagnosis of brain diseases such as seizers, epilepsy, migraine, Alzheimer’s, and dementia. We find these devices assisting paralyzed patients by allowing them to operate computers or robots using their neural activity. In recent years, probe technologies were assisted by rapid advancements in microfabrication and microelectronic technologies and thus are enabling highly functional and robust neural probes which are opening new and exciting avenues in neural sciences and brain machine interfaces. With a wide variety of probes that have been designed, fabricated, and tested to date, this review aims to provide an overview of the advances and recent progress in the microfabrication techniques of neural probes. In addition, we aim to highlight the challenges faced in developing and implementing ultralong multi-site recording probes that are needed to monitor neural activity from deeper regions in the brain. Finally, we review techniques that can improve the biocompatibility of the neural probes to minimize the immune response and encourage neural growth around the electrodes for long term implantation studies.

Multiple-targeted graphene-based nanocarrier for intracellular imaging of mRNAs

International Nuclear Information System (INIS)

Wang, Ying; Li, Zhaohui; Liu, Misha; Xu, Jinjin; Hu, Dehong; Lin, Yuehe; Li, Jinghong

2017-01-01

Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labelled single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis. - Graphical abstract: Schematic illustration of simultaneously multiple mRNAs monitoring inside single living breast cancer cell based on GO nanocarrier. In particular, the fluorescent signals could be monitored when Mn-SOD probe (red) and β-actin probe (green) hybridizes with their mRNA targets inside the living cells. Random probe (orange) was regarded as control probe for the sensing strategy. - Highlights: • A multiple-targeted GO nanocarrier was used for mRNAs imaging and expression changes after drug treatment can be monitored successfully. • Sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) m

Preparation and properties of bio-compatible magnetic Fe3O4 nanoparticles

International Nuclear Information System (INIS)

Chan, H.T.; Do, Y.Y.; Huang, P.L.; Chien, P.L.; Chan, T.S.; Liu, R.S.; Huang, C.Y.; Yang, S.Y.; Horng, H.E.

2006-01-01

In this work, we study the preparation and properties of bio-compatible magnetic nanoparticles for immunoassay and DNA detection. The magnetite (Fe 3 O 4 ) nanoparticles were prepared by a chemical co-precipitation method and dextran was selected as the surfactant to suspend the nanoparticles. Suspended particles associated with avidin followed by biotin were qualitatively analyzed by enzyme-linked immunosorbent assay (ELISA) method. We found further the ethylenediamine blocked activated residual groups efficiently, hence enhancing the attachment of biotin for probing the avidin

Quantification of Different Eubacterium spp. in Human Fecal Samples with Species-Specific 16S rRNA-Targeted Oligonucleotide Probes

OpenAIRE

Schwiertz, Andreas; Le Blay, Gwenaelle; Blaut, Michael

2000-01-01

Species-specific 16S rRNA-targeted, Cy3 (indocarbocyanine)-labeled oligonucleotide probes were designed and validated to quantify different Eubacterium species in human fecal samples. Probes were directed at Eubacterium barkeri, E. biforme, E. contortum, E. cylindroides (two probes), E. dolichum, E. hadrum, E. lentum, E. limosum, E. moniliforme, and E. ventriosum. The specificity of the probes was tested with the type strains and a range of common intestinal bacteria. With one exception, none...

Biocompatible Polymer/Quantum Dots Hybrid Materials: Current Status and Future Developments

Directory of Open Access Journals (Sweden)

Lei Shen

2011-12-01

Full Text Available Quantum dots (QDs are nanometer-sized semiconductor particles with tunable fluorescent optical property that can be adjusted by their chemical composition, size, or shape. In the past 10 years, they have been demonstrated as a powerful fluorescence tool for biological and biomedical applications, such as diagnostics, biosensing and biolabeling. QDs with high fluorescence quantum yield and optical stability are usually synthesized in organic solvents. In aqueous solution, however, their metallic toxicity, non-dissolubility and photo-luminescence instability prevent the direct utility of QDs in biological media. Polymers are widely used to cover and coat QDs for fabricating biocompatible QDs. Such hybrid materials can provide solubility and robust colloidal and optical stability in water. At the same time, polymers can carry ionic or reactive functional groups for incorporation into the end-use application of QDs, such as receptor targeting and cell attachment. This review provides an overview of the recent development of methods for generating biocompatible polymer/QDs hybrid materials with desirable properties. Polymers with different architectures, such as homo- and co-polymer, hyperbranched polymer, and polymeric nanogel, have been used to anchor and protect QDs. The resulted biocompatible polymer/QDs hybrid materials show successful applications in the fields of bioimaging and biosensing. While considerable progress has been made in the design of biocompatible polymer/QDs materials, the research challenges and future developments in this area should affect the technologies of biomaterials and biosensors and result in even better biocompatible polymer/QDs hybrid materials.

Cantilevered probe detector with piezoelectric element

Science.gov (United States)

Adams, Jesse D; Sulchek, Todd A; Feigin, Stuart C

2013-04-30

A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

Selective imaging of cancer cells with a pH-activatable lysosome-targeting fluorescent probe.

Science.gov (United States)

Shi, Rongguang; Huang, Lu; Duan, Xiaoxue; Sun, Guohao; Yin, Gui; Wang, Ruiyong; Zhu, Jun-Jie

2017-10-02

Fluorescence imaging with tumor-specific fluorescent probe has emerged as a tool to aid surgeons in the identification and removal of tumor tissue. We report here a new lysosome-targeting fluorescent probe (NBOH) with BODIPY fluorephore to distinguish tumor tissue out of normal tissue based on different pH environment. The probe exhibited remarkable pH-dependent fluorescence behavior in a wide pH range from 3.0 to 11.0, especially a sensitive pH-dependent fluorescence change at pH range between 3.5 and 5.5, corresponding well to the acidic microenvironment of tumor cells, in aqueous solution. The response time of NBOH was extremely short and the photostability was proved to be good. Toxicity test and fluorescence cell imaging together with a sub-cellular localization study were carried out revealing its low biotoxicity and good cell membrane permeability. And NBOH was successfully applied to the imaging of tumor tissue in tumor-bearing mice suggesting potential application to surgery as a tumor-specific probe. Copyright © 2017 Elsevier B.V. All rights reserved.

Scalable Fabrication Framework of Implantable Ultrathin and Flexible Probes with Biodegradable Sacrificial Layers.

Science.gov (United States)

Jiao, Xiangbing; Wang, Yuan; Qing, Quan

2017-12-13

For long-term biocompatibility and performance, implanted probes need to further reduce their size and mechanical stiffness to match that of the surrounding cells, which, however, makes accurate and minimally invasive insertion operations difficult due to lack of rigidity and brings additional complications in assembling and surgery. Here, we report a scalable fabrication framework of implantable probes utilizing biodegradable sacrificial layers to address this challenge. Briefly, the integrated biodegradable sacrificial layer can dissolve in physiological fluids shortly after implantation, which allows the in situ formation of functional ultrathin film structures off of the initial small and rigid supporting backbone. We show that the dissolution of this layer does not affect the viability and excitability of neuron cells in vitro. We have demonstrated two types of probes that can be used out of the box, including (1) a compact probe that spontaneously forms three-dimensional bend-up devices only after implantation and (2) an ultraflexible probe as thin as 2 μm attached to a small silicon shaft that can be accurately delivered into the tissue and then get fully released in situ without altering its shape and position because the support is fully retracted. We have obtained a >93% yield of the bend-up structure, and its geometry and stiffness can be systematically tuned. The robustness of the ultraflexible probe has been tested in tissue-mimicking agarose gels with <1% fluctuation in the test resistance. Our work provides a general strategy to prepare ultrasmall and flexible implantable probes that allow high insertion accuracy and minimal surgical damages with the best biocompatibility.

Biocompatible fluorescent zein nanoparticles for simultaneous bioimaging and drug delivery application

International Nuclear Information System (INIS)

Girija Aswathy, Ravindran; Sivakumar, Balasubramanian; Brahatheeswaran, Dhandayudhapani; Fukuda, Takahiro; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D

2012-01-01

We report the synthesis of 5-fluorouracil (5-FU) loaded biocompatible fluorescent zein nanoparticles. Zein is the storage protein in corn kernels that has a variety of unique characteristics and functionalities that makes zein valuable in various commercial applications. It is classified as generally recognized as safe (GRAS) by the Food and Drug Administration (FDA). We synthesized zein nanoparticles of around 800 nm in size and conjugated with quantum dot ZnS:Mn. The nanoparticle was in turn encapsulated with the drug 5-FU. The luminescent properties of these nanoparticles were studied by using fluorescence microscopy. The nanoparticles were characterized and the drug release profile was studied. The biocompatibility of zein nanoparticle and the cytotoxicity with drug-loaded nanoparticle was studied in L929 and MCF-7 cell lines. The nanoparticles were successfully employed for cellular imaging. In vitro drug release studies were also performed. The biocompatibility of the nanoparticle showed that nanoparticles at higher concentrations are compatible for cells and are expected to be promising agents for the targeted delivery of drugs in the near future

SU-E-I-81: Targeting of HER2-Expressing Tumors with Dual PET-MR Imaging Probes

Energy Technology Data Exchange (ETDEWEB)

Xu, P; Peng, Y; Sun, M; Yang, X [Suzhou Institute of Biomedical Engineering and Technology Chinese Academy o, Suzhou, Jiangsu (China)

2015-06-15

Purpose: The detection of human epidermal growth factor receptor type 2 (HER2) expression in malignant tumors provides important information influencing patient management. Radionuclide in vivo imaging of HER2 may permit the detection of HER2 in both primary tumors and metastases by a single noninvasive procedure. Trastuzumab, effective in about 15 % of women with breast cancer, downregulates signalling through the Akt/PI3K and MAPK pathways.These pathways modulate metabolism which can be monitored by positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: The relationship between response of HER2 overexpressing tumours and changes in imaging PET or SPECT and MRI will be examined by a integrated bimodal imaging probe.Small (7 kDa) high-affinity anti-HER2 Affibody molecules and KCCYSL targeting peptide may be suitable tracers for visualization of HER2-expressing tumors. Peptide-conjugated iron oxide nanoparticles (Fe3O4 NPs) as MRI imaging and CB-TE2A as PET imaging are integrated into a single synthetic molecule in the HER2 positive cancer. Results: One of targeted contrast bimodal imaging probe agents was synthesized and evaluated to target HER2-expressing tumors in a HER2 positive rat model. We will report the newest results regarding the development of bimodal imaging probes. Conclusion: The preliminary results of the bimodal imaging probe presents high correlation of MRI signal and PET imaging intensity in vivo. This unique feature can hardly be obtained by single model contrast agents. It is envisioned that this bimodal agents can hold great potential for accurate detection of HER2-expressing tumors which are critical for clinical management of the disease.

Biocompatible PEGylated gold nanorods as colored contrast agents for targeted in vivo cancer applications

Science.gov (United States)

Kopwitthaya, Atcha; Yong, Ken-Tye; Hu, Rui; Roy, Indrajit; Ding, Hong; Vathy, Lisa A.; Bergey, Earl J.; Prasad, Paras N.

2010-08-01

In this contribution, we report the use of a PEGylated gold nanorods formulation as a colored dye for tumor labeling in vivo. We have demonstrated that the nanorod-targeted tumor site can be easily differentiated from the background tissues by the 'naked eye' without the need of sophisticated imaging instruments. In addition to tumor labeling, we have also performed in vivo toxicity and biodistribution studies of PEGylated gold nanorods in vivo by using BALB/c mice as the model. In vivo toxicity studies indicated no mortality or adverse effects or weight changes in BALB/c mice treated with PEGylated gold nanorods. This finding will provide useful guidelines in the future development of diagnostic probes for cancer diagnosis, optically guided tumor surgery, and lymph node mapping applications.

Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway

Energy Technology Data Exchange (ETDEWEB)

Schwarzenberg, Johannes [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, Los Angeles, CA (United States); Medical University of Vienna, Department of Pediatrics, Vienna (Austria); Radu, Caius G.; Tran, Andrew Q.; Phelps, Michael E.; Satyamurthy, Nagichettiar [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, Los Angeles, CA (United States); Benz, Matthias; Fueger, Barbara; Czernin, Johannes; Schiepers, Christiaan [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, Los Angeles, CA (United States); Witte, Owen N. [David Geffen School of Medicine, University of California, Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, Los Angeles, CA (United States)

2011-04-15

Deoxycytidine kinase (dCK) is a rate-limiting enzyme in deoxyribonucleoside salvage, a metabolic pathway involved in the production and maintenance of a balanced pool of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis. dCK phosphorylates and therefore activates nucleoside analogs such as cytarabine, gemcitabine, decitabine, cladribine, and clofarabine that are used routinely in cancer therapy. Imaging probes that target dCK might allow stratifying patients into likely responders and nonresponders with dCK-dependent prodrugs. Here we present the biodistribution and radiation dosimetry of three fluorinated dCK substrates, {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC, developed for positron emission tomography (PET) imaging of dCK activity in vivo. PET studies were performed in nine healthy human volunteers, three for each probe. After a transmission scan, the radiopharmaceutical was injected intravenously and three sequential emission scans acquired from the base of the skull to mid-thigh. Regions of interest encompassing visible organs were drawn on the first PET scan and copied to the subsequent scans. Activity in target organs was determined and absorbed dose estimated with OLINDA/EXM. The standardized uptake value was calculated for various organs at different times. Renal excretion was common to all three probes. Bone marrow had higher uptake for L-{sup 18}F-FAC and L-{sup 18}F-FMAC than {sup 18}F-FAC. Prominent liver uptake was seen in L-{sup 18}F-FMAC and L-{sup 18}F-FAC, whereas splenic activity was highest for {sup 18}F-FAC. Muscle uptake was also highest for {sup 18}F-FAC. The critical organ was the bladder wall for all three probes. The effective dose was 0.00524, 0.00755, and 0.00910 mSv/MBq for {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC, respectively. The biodistribution of {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC in humans reveals similarities and differences. Differences may be explained by different probe

Three-dimensional macroporous nanoelectronic networks as minimally invasive brain probes

Science.gov (United States)

Xie, Chong; Liu, Jia; Fu, Tian-Ming; Dai, Xiaochuan; Zhou, Wei; Lieber, Charles M.

2015-12-01

Direct electrical recording and stimulation of neural activity using micro-fabricated silicon and metal micro-wire probes have contributed extensively to basic neuroscience and therapeutic applications; however, the dimensional and mechanical mismatch of these probes with the brain tissue limits their stability in chronic implants and decreases the neuron-device contact. Here, we demonstrate the realization of a three-dimensional macroporous nanoelectronic brain probe that combines ultra-flexibility and subcellular feature sizes to overcome these limitations. Built-in strains controlling the local geometry of the macroporous devices are designed to optimize the neuron/probe interface and to promote integration with the brain tissue while introducing minimal mechanical perturbation. The ultra-flexible probes were implanted frozen into rodent brains and used to record multiplexed local field potentials and single-unit action potentials from the somatosensory cortex. Significantly, histology analysis revealed filling-in of neural tissue through the macroporous network and attractive neuron-probe interactions, consistent with long-term biocompatibility of the device.

Design of mitochondria-targeted colorimetric and ratiometric fluorescent probes for rapid detection of SO2 derivatives in living cells

Science.gov (United States)

Yang, Yutao; Zhou, Tingting; Bai, Bozan; Yin, Caixia; Xu, Wenzhi; Li, Wei

2018-05-01

Two mitochondria-targeted colorimetric and ratiometric fluorescent probes for SO2 derivatives were constructed based on the SO2 derivatives-triggered Michael addition reaction. The probes exhibit high specificity toward HSO3-/SO32- by interrupting their conjugation system resulting in a large ratiometric blue shift of 46-121 nm in their emission spectrum. The two well-resolved emission bands can ensure accurate detection of HSO3-. The detection limits were calculated to be 1.09 and 1.35 μM. Importantly, probe 1 and probe 2 were successfully used to fluorescence ratiometric imaging of endogenous HSO3- in BT-474 cells.

Molecular Imaging of Hepatocellular Carcinoma Xenografts with Epidermal Growth Factor Receptor Targeted Affibody Probes

Directory of Open Access Journals (Sweden)

Ping Zhao

2013-01-01

Full Text Available Hepatocellular carcinoma (HCC is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%–20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo.

Biocompatible PEGylated gold nanorods as colored contrast agents for targeted in vivo cancer applications

Energy Technology Data Exchange (ETDEWEB)

Kopwitthaya, Atcha; Hu Rui; Roy, Indrajit; Ding Hong; Vathy, Lisa A; Bergey, Earl J; Prasad, Paras N [Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260-4200 (United States); Yong, Ken-Tye, E-mail: ktyong@ntu.edu.sg, E-mail: pnprasad@buffalo.edu [School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore)

2010-08-06

In this contribution, we report the use of a PEGylated gold nanorods formulation as a colored dye for tumor labeling in vivo. We have demonstrated that the nanorod-targeted tumor site can be easily differentiated from the background tissues by the 'naked eye' without the need of sophisticated imaging instruments. In addition to tumor labeling, we have also performed in vivo toxicity and biodistribution studies of PEGylated gold nanorods in vivo by using BALB/c mice as the model. In vivo toxicity studies indicated no mortality or adverse effects or weight changes in BALB/c mice treated with PEGylated gold nanorods. This finding will provide useful guidelines in the future development of diagnostic probes for cancer diagnosis, optically guided tumor surgery, and lymph node mapping applications.

Development of tumor-targeted near infrared probes for fluorescence guided surgery.

Science.gov (United States)

Kelderhouse, Lindsay E; Chelvam, Venkatesh; Wayua, Charity; Mahalingam, Sakkarapalayam; Poh, Scott; Kularatne, Sumith A; Low, Philip S

2013-06-19

Complete surgical resection of malignant disease is the only reliable method to cure cancer. Unfortunately, quantitative tumor resection is often limited by a surgeon's ability to locate all malignant disease and distinguish it from healthy tissue. Fluorescence-guided surgery has emerged as a tool to aid surgeons in the identification and removal of malignant lesions. While nontargeted fluorescent dyes have been shown to passively accumulate in some tumors, the resulting tumor-to-background ratios are often poor, and the boundaries between malignant and healthy tissues can be difficult to define. To circumvent these problems, our laboratory has developed high affinity tumor targeting ligands that bind to receptors that are overexpressed on cancer cells and deliver attached molecules selectively into these cells. In this study, we explore the use of two tumor-specific targeting ligands (i.e., folic acid that targets the folate receptor (FR) and DUPA that targets prostate specific membrane antigen (PSMA)) to deliver near-infrared (NIR) fluorescent dyes specifically to FR and PSMA expressing cancers, thereby rendering only the malignant cells highly fluorescent. We report here that all FR- and PSMA-targeted NIR probes examined bind cultured cancer cells in the low nanomolar range. Moreover, upon intravenous injection into tumor-bearing mice with metastatic disease, these same ligand-NIR dye conjugates render receptor-expressing tumor tissues fluorescent, enabling their facile resection with minimal contamination from healthy tissues.

The flush-mounted rail Langmuir probe array designed for the Alcator C-Mod vertical target plate divertor

Science.gov (United States)

Kuang, A. Q.; Brunner, D.; LaBombard, B.; Leccacorvi, R.; Vieira, R.

2018-04-01

An array of flush-mounted and toroidally elongated Langmuir probes (henceforth called rail probes) have been specifically designed for the Alcator C-Mod's vertical target plate divertor and operated over multiple campaigns. The "flush" geometry enables the tungsten electrodes to survive high heat flux conditions in which traditional "proud" tungsten electrodes suffer damage from melting. The toroidally elongated rail-like geometry reduces the influence of sheath expansion, which is an important effect to consider in the design and interpretation of flush-mounted Langmuir probes. The new rail probes successfully operated during C-Mod's FY2015 and FY2016 experimental campaigns with no evidence of damage, despite being regularly subjected to heat flux densities parallel to the magnetic field exceeding ˜1 GW m-2 for short periods of time. A comparison between rail and proud probe data indicates that sheath expansion effects were successfully mitigated by the rail design, extending the use of these Langmuir probes to incident magnetic field line angles as low as 0.5°.

Characterization of the ER-Targeted Low Affinity Ca2+ Probe D4ER

Directory of Open Access Journals (Sweden)

Elisa Greotti

2016-09-01

Full Text Available Calcium ion (Ca2+ is a ubiquitous intracellular messenger and changes in its concentration impact on nearly every aspect of cell life. Endoplasmic reticulum (ER represents the major intracellular Ca2+ store and the free Ca2+ concentration ([Ca2+] within its lumen ([Ca2+]ER can reach levels higher than 1 mM. Several genetically-encoded ER-targeted Ca2+ sensors have been developed over the last years. However, most of them are non-ratiometric and, thus, their signal is difficult to calibrate in live cells and is affected by shifts in the focal plane and artifactual movements of the sample. On the other hand, existing ratiometric Ca2+ probes are plagued by different drawbacks, such as a double dissociation constant (Kd for Ca2+, low dynamic range, and an affinity for the cation that is too high for the levels of [Ca2+] in the ER lumen. Here, we report the characterization of a recently generated ER-targeted, Förster resonance energy transfer (FRET-based, Cameleon probe, named D4ER, characterized by suitable Ca2+ affinity and dynamic range for monitoring [Ca2+] variations within the ER. As an example, resting [Ca2+]ER have been evaluated in a known paradigm of altered ER Ca2+ homeostasis, i.e., in cells expressing a mutated form of the familial Alzheimer’s Disease-linked protein Presenilin 2 (PS2. The lower Ca2+ affinity of the D4ER probe, compared to that of the previously generated D1ER, allowed the detection of a conspicuous, more clear-cut, reduction in ER Ca2+ content in cells expressing mutated PS2, compared to controls.

Translational Applications of Nanodiamonds: From Biocompatibility to Theranostics

Science.gov (United States)

Moore, Laura Kent

Nanotechnology marks the next phase of development for drug delivery, contrast agents and gene therapy. For these novel systems to achieve success in clinical translation we must see that they are both effective and safe. Diamond nanoparticles, also known as nanodiamonds (NDs), have been gaining popularity as molecular delivery vehicles over the last decade. The uniquely faceted, carbon nanoparticles possess a number of beneficial properties that are being harnessed for applications ranging from small-molecule drug delivery to biomedical imaging and gene therapy. In addition to improving the effectiveness of a variety of therapeutics and contrast agents, initial studies indicate that NDs are biocompatible. In this work we evaluate the translational potential of NDs by demonstrating efficacy in molecular delivery and scrutinizing particle tolerance. Previous work has demonstrated that NDs are effective vehicles for the delivery of anthracycline chemotherapeutics and gadolinium(III) based contrast agents. We have sought to enhance the gains made in both areas through the addition of active targeting. We find that ND-mediated targeted delivery of epirubicin to triple negative breast cancers induces tumor regression and virtually eliminates drug toxicities. Additionally, ND-mediated delivery of the MRI contrast agent ProGlo boosts the per gadolinium relaxivity four fold, eliminates water solubility issues and effectively labels progesterone receptor expressing breast cancer cells. Both strategies open the door to the development of targeted, theranostic constructs based on NDs, capable of treating and labeling breast cancers at the same time. Although we have seen that NDs are effective vehicles for molecular delivery, for any nanoparticle to achieve clinical utility it must be biocompatible. Preliminary research has shown that NDs are non-toxic, however only a fraction of the ND-subtypes have been evaluated. Here we present an in depth analysis of the cellular

Radiolabeled Probes Targeting Hypoxia-Inducible Factor-1-Active Tumor Microenvironments

Directory of Open Access Journals (Sweden)

Masashi Ueda

2014-01-01

Full Text Available Because tumor cells grow rapidly and randomly, hypoxic regions arise from the lack of oxygen supply in solid tumors. Hypoxic regions in tumors are known to be resistant to chemotherapy and radiotherapy. Hypoxia-inducible factor-1 (HIF-1 expressed in hypoxic regions regulates the expression of genes related to tumor growth, angiogenesis, metastasis, and therapy resistance. Thus, imaging of HIF-1-active regions in tumors is of great interest. HIF-1 activity is regulated by the expression and degradation of its α subunit (HIF-1α, which is degraded in the proteasome under normoxic conditions, but escapes degradation under hypoxic conditions, allowing it to activate transcription of HIF-1-target genes. Therefore, to image HIF-1-active regions, HIF-1-dependent reporter systems and injectable probes that are degraded in a manner similar to HIF-1α have been recently developed and used in preclinical studies. However, no probe currently used in clinical practice directly assesses HIF-1 activity. Whether the accumulation of 18F-FDG or 18F-FMISO can be utilized as an index of HIF-1 activity has been investigated in clinical studies. In this review, the current status of HIF-1 imaging in preclinical and clinical studies is discussed.

Hyaluronan functionalizing QDs as turn-on fluorescent probe for targeted recognition CD44 receptor

Science.gov (United States)

Zhou, Shang; Huo, Danqun; Hou, Changjun; Yang, Mei; Fa, Huanbao

2017-09-01

The recognition of tumor markers in living cancer cells has attracted increasing interest. In the present study, the turn-on fluorescence probe was designed based on the fluorescence of thiolated chitosan-coated CdTe QDs (CdTe/TCS QDs) quenched by hyaluronan, which could provide the low background signal for sensitive cellular imaging. This system is expected to offer specific recognition of CD44 receptor over other substances owing to the specific affinity of hyaluronan and CD44 receptor ( 8-9 kcal/mol). The probe is stable in aqueous and has little toxicity to living cells; thus, it can be utilized for targeted cancer cell imaging. The living lung cancer cell imaging experiments further demonstrate its value in recognizing cell-surface CD44 receptor with turn-on mode. In addition, the probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. And, the western blot test further confirmed that the expression level of the CD44 receptor in lung cancer cells is different. Therefore, this probe may be potentially applied in recognizing lung cancer cells with higher contrast and sensitivity and provide new tools for cancer prognosis and therapy. [Figure not available: see fulltext.

Development of chitosan-coated gold nanoflowers as SERS-active probes

Science.gov (United States)

Xu, Dan; Gu, Jiangjiang; Wang, Weina; Yu, Xuehai; Xi, Kai; Jia, Xudong

2010-09-01

Surface-enhanced Raman scattering (SERS) has been intensely researched for many years as a potential technique for highly sensitive detection. This work, through the reduction of HAuCl4 with pyrrole in aqueous solutions, investigated a facile one-pot synthesis of flower-like Au nanoparticles with rough surfaces. The formation process of the Au nanoflowers (AuNFs) was carefully studied, and a spontaneous assembly mechanism was proposed based on the time-course experimental results. The key synthesis strategy was to use pyrrole as a weak particle stabilizing and reducing agent to confine crystal growth in the limited ligand protection region. The nanometer-scale surface roughness of AuNFs provided several hot spots on a single particle, which significantly increased SERS enhancement. Good biocompatible stable Raman-active probes were synthesized by coating AuNFs with chitosan. The conservation of the SERS effects in living cells suggested that the chitosan-capped AuNFs could be suitable for highly sensitive detection and have potential for targeting of tumors in vivo.

Quantification of different Eubacterium spp. in human fecal samples with species-specific 16S rRNA-targeted oligonucleotide probes.

Science.gov (United States)

Schwiertz, A; Le Blay, G; Blaut, M

2000-01-01

Species-specific 16S rRNA-targeted, Cy3 (indocarbocyanine)-labeled oligonucleotide probes were designed and validated to quantify different Eubacterium species in human fecal samples. Probes were directed at Eubacterium barkeri, E. biforme, E. contortum, E. cylindroides (two probes), E. dolichum, E. hadrum, E. lentum, E. limosum, E. moniliforme, and E. ventriosum. The specificity of the probes was tested with the type strains and a range of common intestinal bacteria. With one exception, none of the probes showed cross-hybridization under stringent conditions. The species-specific probes were applied to fecal samples obtained from 12 healthy volunteers. E. biforme, E. cylindroides, E. hadrum, E. lentum, and E. ventriosum could be determined. All other Eubacterium species for which probes had been designed were under the detection limit of 10(7) cells g (dry weight) of feces(-1). The cell counts obtained are essentially in accordance with the literature data, which are based on colony counts. This shows that whole-cell in situ hybridization with species-specific probes is a valuable tool for the enumeration of Eubacterium species in feces.

A rheological and microscopical characterization of biocompatible ferrofluids

International Nuclear Information System (INIS)

Nowak, J.; Wolf, D.; Odenbach, S.

2014-01-01

There is an increasing interest in suspensions of magnetic nanoparticles in the biomedical area. Those ferrofluids are e.g. used for magnetic resonance imaging and emerging research focuses on employing the fluids for magnetic drug targeting or magnetic particle heating as a potential treatment for cancer. For these applications the knowledge of the suspensions' thermophysical properties is of major interest to guarantee a safe and effective application. Therefore the flow behavior cannot be neglected as it might significantly influence the execution of the aforementioned applications. In this experimental study two biocompatible ferrofluids were investigated. Rheological measurements were carried out using rotational rheometry. To allow an interpretation of the fluids' behavior the microscopic make-up was investigated using dynamic light scattering and transmission electron microscopy. Measurements of diluted ferrofluids were carried out as a first step to simulate the rheological behavior reflecting the concentration of magnetic nanoparticles found in blood flow for most biomedical applications of such fluids. The detected strong effects show the potential to significantly influence application and handling of the biocompatible ferrofluids in the medical area and should therefore be taken into account for further research as well as for the application of such fluids. - Highlights: • The rheology of biocompatible multicore ferrofluids is influenced by magnetic fields. • The flow curves can be described by the Herschel–Bulkley model. • A connection between the magnetoviscous effect and the particle size is found. • The strong magnetoviscous effect exists even if the fluids are diluted. • The connection between the effect and the dilution is mathematically described

Optical fiber biocompatible sensors for monitoring selective treatment of tumors via thermal ablation

Science.gov (United States)

Tosi, Daniele; Poeggel, Sven; Dinesh, Duraibabu B.; Macchi, Edoardo G.; Gallati, Mario; Braschi, Giovanni; Leen, Gabriel; Lewis, Elfed

2015-09-01

Thermal ablation (TA) is an interventional procedure for selective treatment of tumors, that results in low-invasive outpatient care. The lack of real-time control of TA is one of its main weaknesses. Miniature and biocompatible optical fiber sensors are applied to achieve a dense, multi-parameter monitoring, that can substantially improve the control of TA. Ex vivo measurements are reported performed on porcine liver tissue, to reproduce radiofrequency ablation of hepatocellular carcinoma. Our measurement campaign has a two-fold focus: (1) dual pressure-temperature measurement with a single probe; (2) distributed thermal measurement to estimate point-by-point cells mortality.

Differential detection of type II methanotrophic bacteria in acidic peatlands using newly developed 16S rRNA-targeted fluorescent oligonucleotide probes.

Science.gov (United States)

Dedysh, Svetlana N; Dunfield, Peter F; Derakshani, Manigee; Stubner, Stephan; Heyer, Jürgen; Liesack, Werner

2003-04-01

Abstract Based on an extensive 16S rRNA sequence database for type II methanotrophic bacteria, a set of 16S rRNA-targeted oligonucleotide probes was developed for differential detection of specific phylogenetic groups of these bacteria by fluorescence in situ hybridisation (FISH). This set of oligonucleotides included a genus-specific probe for Methylocystis (Mcyst-1432) and three species-specific probes for Methylosinus sporium (Msins-647), Methylosinus trichosporium (Msint-1268) and the recently described acidophilic methanotroph Methylocapsa acidiphila (Mcaps-1032). These novel probes were applied to further characterise the type II methanotroph community that was detected in an acidic Sphagnum peat from West Siberia in a previous study (Dedysh et al. (2001) Appl. Environ. Microbiol. 67, 4850-4857). The largest detectable population of indigenous methanotrophs simultaneously hybridised with a group-specific probe targeting all currently known Methylosinus/Methylocystis spp. (M-450), with a genus-specific probe for Methylocystis spp. (Mcyst-1432), and with an additional probe (Mcyst-1261) that had been designed to target a defined phylogenetic subgroup of Methylocystis spp. The same subgroup of Methylocystis was also detected in acidic peat sampled from Sphagnum-dominated wetland in northern Germany. The population size of this peat-inhabiting Methylocystis subgroup was 2.0+/-0.1x10(6) cells g(-1) (wet weight) of peat from Siberia and 5.5+/-0.5x10(6) cells g(-1) of peat from northern Germany. This represented 60 and 95%, respectively, of the total number of methanotroph cells detected by FISH in these two wetland sites. Other major methanotroph populations were M. acidiphila and Methylocella palustris. Type I methanotrophs accounted for not more than 1% of total methanotroph cells. Neither M. trichosporium nor M. sporium were detected in acidic Sphagnum peat.

A nanobody targeting carcinoembryonic antigen as a promising molecular probe for non-small cell lung cancer.

Science.gov (United States)

Wang, Hao; Meng, Ai-Min; Li, Sheng-Hua; Zhou, Xiao-Liang

2017-07-01

Carcinoembryonic antigen (CEA) is a biomarker and therapy target for non‑small cell lung cancer (NSCLC), which is the most common type of lung cancer. Nanobodies with high target specificity are promising candidates to function as anti‑CEA probes. In the present study, the targeting effects of an anti‑CEA nanobody obtained from phage display were investigated using technetium‑99 m (99mTc) and fluorescence labeling. In vitro binding and immunofluorescent staining assays, as well as in vivo blood clearance and biodistribution assays were performed. High specificity and affinity of the nanobody for CEA‑positive H460 cells was observed in vitro. The pharmacokinetics assay of the 99mTc‑nanobody in Wistar rats demonstrated that the nanobody had appropriate T1/2α and T1/2β, which were 20.2 and 143.5 min, respectively. The biodistribution assay using H460 xenograft‑bearing nude mice demonstrated a high ratio of signal in tumor compared with background, which confirmed that the nanobody may be useful as a molecular probe for CEA‑positive cancer, particularly in NSCLC.

Characterisation of target plasma required for REB-plasma interaction studies using cylindrical Langmuir probes

International Nuclear Information System (INIS)

Roychowdhury, P.; Paithankar, A.S.; Iyyengar, S.K.; Rohatgi, V.K.

1987-01-01

The target plasma required for relativistic electron beam (REB)-plasma interaction studies has been generated by coaxial plasma gun. The measurement of electron density and temperature has been carried out using cylindrical Langmuir probes. Probes both oriented parallel and transverse to the flow have been used. The spatial as well as temporal variation of electron density and temperature have been studied. The typical electron density and temperature measured by probe were in the range of 9.0-3.5 x 10 13 cm -3 and 5-7 eV respectively. The typical e-folding decay time of density was 6.2 μs, while no appreciable change in electron temperature was observed until 10 μs after the peak density. The density decays by about 50% at distance of 30 cm from the gun. The plasma flow velocity has been measured by the time of flight technique and was found to be 2.5 x 10 6 cm s -1 . The plasma radius measured by dosimeter film, at distance of 30 cm from the gun was 3 cm. (author)

Probe-diverse ptychography

Energy Technology Data Exchange (ETDEWEB)

Peterson, I., E-mail: isaac.russellpeterson@rmit.edu.au [ARC Centre of Excellence for Coherent X-ray Science, the University of Melbourne, School of Physics, Victoria 3010 (Australia); Harder, R. [Advanced Photon Source, Argonne National Laboratory, Argonne, IL 60439 (United States); Robinson, I.K. [Research Complex at Harwell, Didcot, Oxfordshire OX11 0DE (United Kingdom); London Centre for Nanotechnology, University College London, London WC1H 0AH (United Kingdom)

2016-12-15

We propose an extension of ptychography where the target sample is scanned separately through several probes with distinct amplitude and phase profiles and a diffraction image is recorded for each probe and each sample translation. The resulting probe-diverse dataset is used to iteratively retrieve high-resolution images of the sample and all probes simultaneously. The method is shown to yield significant improvement in the reconstructed sample image compared to the image obtained using the standard single-probe ptychographic phase-retrieval scheme.

Synthesis and characterization of biocompatible hydroxyapatite ...

Indian Academy of Sciences (India)

https://www.ias.ac.in/article/fulltext/boms/026/07/0655-0660. Keywords. Bioceramics; hyperthermia; ferrite; biocompatible coating. Abstract. Ferrite particles coated with biocompatible phases can be used for hyperthermia treatment of cancer. We have synthesized substituted calcium hexaferrite, which is not stable on its own ...

Fabrication and wireless micromanipulation of magnetic-biocompatible microrobots using microencapsulation for microrobotics and microfluidics applications.

Science.gov (United States)

Li, Hui; Zhang, Jinyong; Zhang, Nannan; Kershaw, Joe; Wang, Lei

2016-12-01

It is important to fabricate biocompatible and chemical-resistant microstructures that can be powered and controlled without a tether in fluid environment for applications when contamination must be avoided, like cell manipulation, and applications where connecting the power source to the actuator would be cumbersome, like targeted delivery of chemicals. In this work, a novel fabrication method was described to encapsulate magnetic composite into pure SU-8 structures, enabling the truly microscale ferromagnetic microrobots biocompatible and chemical resistant. The microrobots were developed using the simple multilayer photolithography that allows us to mass produce and were actuated contact-free by external magnetic field to complete micromanipulations of micro-objects. The microrobots were actuated moving along a preplanned path to transport a glass microsphere object at an approximately average speed of 1.1 mm/sec and can be operated to rotate, aim at targets and collect objects.

Development of probes for bioanalytic applications of the surface-enhanced Raman scattering; Entwicklung neuer Sonden fuer bioanalytische Anwendungen der oberflaechenverstaerkten Raman-Streuung

Energy Technology Data Exchange (ETDEWEB)

Matschulat, Andrea Isabel

2011-07-01

Surface-enhanced Raman scattering (SERS) has been established as a versatile tool for probing and labeling in analytical applications, based on the vibrational spectra of samples as well as label molecules in the proximity of noble metal nanostructures. The aim of this work was the construction of novel SERS hybrid probes. The hybrid probes consisted of Au and Ag nanoparticles and reporter molecules, as well as a targeting unit. The concept for the SERS hybrid probe design was followed by experiments comprising characterization techniques such as UV/Vis-spectroscopy (UV/Vis), Transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS), respectively. SERS experiments were performed for studying and optimizing the plasmonic properties of nanoparticles with respect to their enhancement capabilities. The SERS-probes had to meet following requirements: biocompatibility, stability in physiological media, and enhancement of Raman-signals from Raman reporter molecules enabling the identification of different probes even in a complex biological environment. Au and Ag nanoaggregates were found to be the most appropriate SERS substrates for the hybrid probe design. The utilization of Raman reporters enabled the identification of different SERS probes in multiplexing experiments. In particular, the multiplexing capability of ten various reporter molecules para-aminobenzenethiol, 2-naphthalenethiol, crystal violet, rhodamine (B) isothiocyanate, fluorescein isothiocyanate, 5,5'dithiobis(2-nitrobenzoic acid), para-mercaptobenzoic acid, acridine orange, safranine O und nile blue was studied using NIR-SERS excitation. As demonstrated by the results the reporters could be identified through their specific Raman signature even in the case of high structural similarity. Chemical separation analysis of the reporter signatures was performed in a trivariate approach, enabling the discrimination through an automated calculation of specific band ratios. The trivariate

Mobile Game Probes

DEFF Research Database (Denmark)

Borup Lynggaard, Aviaja

2006-01-01

This paper will examine how probes can be useful for game designers in the preliminary phases of a design process. The work is based upon a case study concerning pervasive mobile phone games where Mobile Game Probes have emerged from the project. The new probes are aimed towards a specific target...... group and the goal is to specify the probes so they will cover the most relevant areas for our project. The Mobile Game Probes generated many interesting results and new issues occurred, since the probes came to be dynamic and favorable for the process in new ways....

A flavone-based turn-on fluorescent probe for intracellular cysteine/homocysteine sensing with high selectivity.

Science.gov (United States)

Zhang, Jian; Lv, Yanlin; Zhang, Wei; Ding, Hui; Liu, Rongji; Zhao, Yongsheng; Zhang, Guangjin; Tian, Zhiyuan

2016-01-01

A new type of flavone-based fluorescent probe (DMAF) capable of cysteine (Cys)/homocysteine (Hcy) sensing with high selectivity over other amino acids was developed. Such type of probe undergoes Cys/Hcy-mediated cyclization reaction with the involvement of its aldehyde group, which suppresses of the photoinduced electron transfer (PET) process of the probe molecule and consequently leads to the enhancement of fluorescence emission upon excitation using visible light. The formation of product of the Cys/Hcy-mediated cyclization reaction was confirmed and the preliminary fluorescence imaging experiments revealed the biocompatibility of the as-prepared probe and validated its practicability for intracellular Cys/Hcy sensing. Copyright © 2015 Elsevier B.V. All rights reserved.

Detection of Misdistribution of Tyrosinase from Melanosomes to Lysosomes and Its Upregulation under Psoralen/Ultraviolet A with a Melanosome-Targeting Tyrosinase Fluorescent Probe.

Science.gov (United States)

Zhou, Jin; Shi, Wen; Li, Lihong; Gong, Qiuyu; Wu, Xiaofeng; Li, Xiaohua; Ma, Huimin

2016-04-19

Tyrosinase is regarded as an important biomarker of melanoma cancer, and its metabolism is closely related to some severe skin diseases such as vitiligo. Since tyrosinase is mainly located in the melanosomes of melanocytes, a probe that can specifically detect and image tysosinase in melanosomes would be in urgent demand to study the behavior of the enzyme in cells, but unfortunately, no melanosome-targeting tyrosinase fluorescent probe has been reported so far to the best of our knowledge. In this work, we have developed such a new probe, Mela-TYR, which bears morpholine as a melanosome-targeting group and 4-aminophenol as a tyrosinase reaction group. The probe exhibits not only a highly sensitive and selective off-on response to tyrosinase via oxidization cleavage, but also an accurate targeting ability toward the acidic organelles of melanosomes and lyososomes, which is validated by colocalization experiments with mCherry-tagged melanosomes as well as DND-99 (a commercial dye). The probe has been used to image the relative contents of tyrosinase in different cells. Notably, because of the tyrosinase deficiency in normal lysosomes, the probe only fluoresces in melanosomes in principle although it can accumulate in other acidic organelles like lysosomes. By virtue of this property, the misdistribution of tyrosinase from melanosomes to lysosomes in murine melanoma B16 cells under the stimulation of inulavosin is imaged in real time for the first time. Moreover, the upregulation of melanosomal tyrosinase in live B16 cells under the stimulation of psoralen/ultraviolet A is detected with our probe, and this upregulation is further verified by standard colorimetric assay. The probe provides a simple, visual method to study the metabolism of tyrosinase in cells and shows great potential in clinical diagnosis and treatments of tyrosinase-associated diseases.

Biocompatible KMnF3 nanoparticular contrast agent with proper plasma retention time for in vivo magnetic resonance imaging.

Science.gov (United States)

Liu, Zhi-jun; Song, Xiao-xia; Xu, Xian-zhu; Tang, Qun

2014-04-18

Nanoparticular MRI contrast agents are rapidly becoming suitable for use in clinical diagnosis. An ideal nanoparticular contrast agent should be endowed with high relaxivity, biocompatibility, proper plasma retention time, and tissue-specific or tumor-targeting imaging. Herein we introduce PEGylated KMnF3 nanoparticles as a new type of T1 contrast agent. Studies showed that the nanoparticular contrast agent revealed high bio-stability with bovine serum albumin in PBS buffer solution, and presented excellent biocompatibility (low cytotoxicity, undetectable hemolysis and hemagglutination). Meanwhile the new contrast agent possessed proper plasma retention time (circulation half-life t1/2 is approximately 2 h) in the body of the administrated mice. It can be delivered into brain vessels and maintained there for hours, and is mostly cleared from the body within 48 h, as demonstrated by time-resolved MRI and Mn-biodistribution analysis. Those distinguishing features make it suitable to obtain contrast-enhanced brain magnetic resonance angiography. Moreover, through the process of passive targeting delivery, the T1 contrast agent clearly illuminates a brain tumor (glioma) with high contrast image and defined shape. This study demonstrates that PEGylated KMnF3 nanoparticles represent a promising biocompatible vascular contrast agent for magnetic resonance angiography and can potentially be further developed into an active targeted tumor MRI contrast agent.

Targets and probes for non-invasive imaging of β-cells

Energy Technology Data Exchange (ETDEWEB)

Jodal, Andreas; Behe, Martin [Paul Scherrer Institut, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Schibli, Roger [Paul Scherrer Institut, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

2017-04-15

β-cells, located in the islets of the pancreas, are responsible for production and secretion of insulin and play a crucial role in blood sugar regulation. Pathologic β-cells often cause serious medical conditions affecting blood glucose level, which severely impact life quality and are life-threatening if untreated. With 347 million patients, diabetes is one of the most prevalent diseases, and will continue to be one of the largest socioeconomic challenges in the future. The diagnosis still relies mainly on indirect methods like blood sugar measurements. A non-invasive diagnostic imaging modality would allow direct evaluation of β-cell mass and would be a huge step towards personalized medicine. Hyperinsulinism is another serious condition caused by β-cells that excessively secrete insulin, like for instance β-cell hyperplasia and insulinomas. Treatment options with drugs are normally not curative, whereas curative procedures usually consist of the resection of affected regions for which, however, an exact localization of the foci is necessary. In this review, we describe potential tracers under development for targeting β-cells with focus on radiotracers for PET and SPECT imaging, which allow the non-invasive visualization of β-cells. We discuss either the advantages or limitations for the various tracers and modalities. This article concludes with an outlook on future developments and discuss the potential of new imaging probes including dual probes that utilize functionalities for both a radioactive and optical moiety as well as for theranostic applications. (orig.)

Targets and probes for non-invasive imaging of β-cells

International Nuclear Information System (INIS)

Jodal, Andreas; Behe, Martin; Schibli, Roger

2017-01-01

β-cells, located in the islets of the pancreas, are responsible for production and secretion of insulin and play a crucial role in blood sugar regulation. Pathologic β-cells often cause serious medical conditions affecting blood glucose level, which severely impact life quality and are life-threatening if untreated. With 347 million patients, diabetes is one of the most prevalent diseases, and will continue to be one of the largest socioeconomic challenges in the future. The diagnosis still relies mainly on indirect methods like blood sugar measurements. A non-invasive diagnostic imaging modality would allow direct evaluation of β-cell mass and would be a huge step towards personalized medicine. Hyperinsulinism is another serious condition caused by β-cells that excessively secrete insulin, like for instance β-cell hyperplasia and insulinomas. Treatment options with drugs are normally not curative, whereas curative procedures usually consist of the resection of affected regions for which, however, an exact localization of the foci is necessary. In this review, we describe potential tracers under development for targeting β-cells with focus on radiotracers for PET and SPECT imaging, which allow the non-invasive visualization of β-cells. We discuss either the advantages or limitations for the various tracers and modalities. This article concludes with an outlook on future developments and discuss the potential of new imaging probes including dual probes that utilize functionalities for both a radioactive and optical moiety as well as for theranostic applications. (orig.)

Fabrication of biocompatible free-standing nanopatterned films for primary neuronal cultures

KAUST Repository

Cesca, F.; Limongi, T.; Accardo, A.; Rocchi, A.; Orlando, M.; Shalabaeva, V.; Di Fabrizio, Enzo M.; Benfenati, F.

2014-01-01

Devising and constructing biocompatible devices for nervous system regeneration is an extremely challenging task. Besides tackling the issue of biocompatibility, biomaterials for neuroscience applications should mimic the complex environment of the extracellular matrix, which in vivo provides neurons with a series of cues and signals to guide cells towards their appropriate targets. In this work, a novel nanopatterned biocompatible poly-ε-caprolactone (PCL) film is realized to assist the attachment and growth of primary hippocampal neurons. Costly and time-consuming processes can be avoided using plasma-surface nanotexturing obtained by a mixed gas SF6/Ar at −5 °C. The intrinsic composition and line topography of nanopatterned PCL ensure healthy development of the neuronal network, as shown by confocal microscopy, by analysing the expression of a range of neuronal markers typical of mature cultures, as well as by scanning electron microscopy. In addition, we show that surface nanopatterning improves differentiation of neurons compared to flat PCL films, while no neural growth was observed on either flat or nanopatterned substrates in the absence of a poly-D-lysine coating. Thus, we successfully optimized a nanofabrication protocol to obtain nanostructured PCL layers endowed with several mechanical and structural characteristics that make them a promising, versatile tool for future tissue engineering studies aimed at neural tissue regeneration.

Fabrication of biocompatible free-standing nanopatterned films for primary neuronal cultures

KAUST Repository

Cesca, F.

2014-09-10

Devising and constructing biocompatible devices for nervous system regeneration is an extremely challenging task. Besides tackling the issue of biocompatibility, biomaterials for neuroscience applications should mimic the complex environment of the extracellular matrix, which in vivo provides neurons with a series of cues and signals to guide cells towards their appropriate targets. In this work, a novel nanopatterned biocompatible poly-ε-caprolactone (PCL) film is realized to assist the attachment and growth of primary hippocampal neurons. Costly and time-consuming processes can be avoided using plasma-surface nanotexturing obtained by a mixed gas SF6/Ar at −5 °C. The intrinsic composition and line topography of nanopatterned PCL ensure healthy development of the neuronal network, as shown by confocal microscopy, by analysing the expression of a range of neuronal markers typical of mature cultures, as well as by scanning electron microscopy. In addition, we show that surface nanopatterning improves differentiation of neurons compared to flat PCL films, while no neural growth was observed on either flat or nanopatterned substrates in the absence of a poly-D-lysine coating. Thus, we successfully optimized a nanofabrication protocol to obtain nanostructured PCL layers endowed with several mechanical and structural characteristics that make them a promising, versatile tool for future tissue engineering studies aimed at neural tissue regeneration.

Development and use of fluorescent 16S rRNA-targeted probes for the specific detection of Methylophaga species by in situ hybridization in marine sediments.

Science.gov (United States)

Janvier, Monique; Regnault, Béatrice; Grimont, Patrick

2003-09-01

Methylotrophic bacteria are widespread in nature. They may play an important role in the cycling of carbon and in the metabolism of dimethylsulfide in a marine environment. Bacteria belonging to the genus Methylophaga are a unique group of aerobic, halophilic, non-methane-utilizing methylotrophs. Two 16S rRNA-targeted oligonucleotide probes were developed for the specific detection of Methylophaga species, marine methylobacteria, by fluorescence in situ hybridization. Probe MPH-730 was highly specific for all members of the genus Methylophaga while probe MPHm-994 targeted exclusively M. marina. The application of these probes were demonstrated by the detection of Methylophaga species in enrichment cultures from various marine sediments. All isolates recovered were visualized by using the genus specific probe MPH-730. The results were confirmed by 16S rDNA sequencing which demonstrated that all selected isolates belong to Methylophaga. Five isolates could be detected by the M. marina-specific probe MPHm-994 and were confirmed by rRNA gene restriction pattern (ribotyping). With the development of these specific probes, fluorescence in situ hybridization shows that the genus Methylophaga is widespread in marine samples.

A lysosome-targetable turn-on fluorescent probe for the detection of thiols in living cells based on a 1,8-naphthalimide derivative

Science.gov (United States)

Liang, Beibei; Wang, Baiyan; Ma, Qiujuan; Xie, Caixia; Li, Xian; Wang, Suiping

2018-03-01

Biological thiols, like cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), play crucial roles in biological systems and in lysosomal processes. Highly selective probes for detecting biological thiols in lysomes of living cells are rare. In this work, a lysosome-targetable turn-on fluorescent probe for the detection of thiols in living cells was designed and synthesized based on a 1,8-naphthalimide derivative. The probe has a 4-(2-aminoethyl)morpholine unit as a lysosome-targetable group and an acrylate group as the thiol recognition unit as well as a fluorescence quencher. In the absence of biothiols, the probe displayed weak fluorescence due to the photoinduced electron transfer (PET) process. Upon the addition of biothiols, the probe exhibited an enhanced fluorescence emission centered at 550 nm due to cleavage of the acrylate moiety. The probe had high selectivity toward biothiols. Moreover, the probe features fast response time, excitation in the visible region and ability of working in a wide pH range. The linear response range covers a concentration range of Cys from 1.5 × 10- 7 to 1.0 × 10- 5 mol·L- 1 and the detection limit is 6.9 × 10- 8 mol·L- 1 for Cys. The probe has been successfully applied to the confocal imaging of biothiols in lysosomes of A549 cells with low cell toxicity. Furthermore, the method was successfully applied to the determination of thiols in a complex multicomponent mixture such as human serum, which suggests our proposed method has great potential for diagnostic purposes. All of such good properties prove it can be used to monitor biothiols in lysosomes of living cells and to be a good fluorescent probe for the selective detection of thiols.

Measurement of the target current by inductive probe during laser interaction on terawatt laser system PALS

Czech Academy of Sciences Publication Activity Database

Cikhardt, Jakub; Krása, Josef; De Marco, Massimo; Pfeifer, Miroslav; Velyhan, Andriy; Krouský, Eduard; Cikhardtová, B.; Klír, Daniel; Řezáč, Karel; Ullschmied, Jiří; Skála, Jiří; Kubeš, P.; Kravárik, J.

2014-01-01

Roč. 85, č. 10 (2014), s. 103507-103507 ISSN 0034-6748 R&D Projects: GA MŠk LM2010014; GA MŠk(CZ) LG13029; GA ČR GAP205/12/0454; GA MŠk EE2.3.20.0279 Grant - others:LaserZdroj (OP VK 3)(XE) CZ.1.07/2.3.00/20.0279 Institutional support: RVO:61389021 ; RVO:68378271 Keywords : laser PALS * laser-target interaction * target current * inductive probe Subject RIV: BL - Plasma and Gas Discharge Physics; BL - Plasma and Gas Discharge Physics (FZU-D) Impact factor: 1.614, year: 2014 http://dx.doi.org/10.1063/1.4898016

A Molecularly Targeted Theranostic Probe for Ovarian Cancer

Science.gov (United States)

Chen, Wenxue; Bardhan, Rizia; Bartels, Marc; Perez-Torres, Carlos; Pautler, Robia G.; Halas, Naomi J.; Joshi, Amit

2014-01-01

Overexpression of the human epidermal growth factor receptor (HER) family has been implicated in ovarian cancer because of its participation in signaling pathway regulating cellular proliferation, differentiation, motility, and survival. Currently, effective diagnostic and therapeutic schemes are lacking for treating ovarian cancer and consequently ovarian cancer has a high mortality rate. While HER2 receptor expression does not usually affect the survival rates of ovarian cancer to the same extent as in breast cancer, it can be employed as a docking site for directed nanotherapies in cases with de novo or acquired chemotherapy resistance. In this study, we have exploited a novel gold nanoshell-based complex (nanocomplex) for targeting, dual modal imaging, and photothermal therapy of HER2 overexpressing and drug resistant ovarian cancer OVCAR3 cells in vitro. The nanocomplexes are engineered to simultaneously provide contrast as fluorescence optical imaging probe and a magnetic resonance imaging (MRI) agent. Both immunofluorescence staining and MRI successfully demonstrate that nanocomplex-anti-HER2 conjugates specifically bind to OVCAR3 cells as opposed to the control, MDA-MB-231 cells, which have low HER2 expression. In addition, nanocomplexes targeted to OVCAR3 cells, when irradiated with near infrared (NIR) laser result in selective destruction of cancer cells through photothermal ablation. We also demonstrate that NIR light therapy and the nanocomplexes by themselves are non-cytotoxic in vitro. To the best of our knowledge, this is the first demonstration of a successful integration of dual modal bioimaging with photothermal cancer therapy for treatment of ovarian cancer. Based on their efficacy in vitro, these nanocomplexes are highly promising for image guided photo-thermal therapy of ovarian cancer as well as other HER2 overexpressing cancers. PMID:20371708

Biocompatibility of polyaniline

Czech Academy of Sciences Publication Activity Database

Humpolíček, P.; Kašpárková, V.; Saha, P.; Stejskal, Jaroslav

2012-01-01

Roč. 162, 7/8 (2012), s. 722-727 ISSN 0379-6779 R&D Projects: GA ČR GA202/09/1626 Institutional research plan: CEZ:AV0Z40500505 Keywords : conducting polymer * polyaniline * biocompatibility Subject RIV: BK - Fluid Dynamics Impact factor: 2.109, year: 2012

Synthesis and Bioevaluation of Iodine-131 Directly Labeled Cyclic RGD-PEGylated Gold Nanorods for Tumor-Targeted Imaging

Directory of Open Access Journals (Sweden)

Yingying Zhang

2017-01-01

Full Text Available Introduction. Radiolabeled gold nanoparticles play an important role in biomedical application. The aim of this study was to prepare iodine-131 (131I-labeled gold nanorods (GNRs conjugated with cyclic RGD and evaluate its biological characteristics for targeted imaging of integrin αvβ3-expressing tumors. Methods. HS-PEG(5000-COOH molecules were applied to replace CTAB covering the surface of bare GNRs for better biocompatibility, and c(RGDfK peptides were conjugated onto the carboxyl terminal of GNR-PEG-COOH via EDC/NHS coupling reactions. The nanoconjugate was characterized, and 131I was directly tagged on the surface of GNRs via AuI bonds for SPECT/CT imaging. We preliminarily studied the characteristics of the probe and its feasibility for tumor-targeting SPECT/CT imaging. Results. The [131I]GNR-PEG-cRGD probe was prepared in a simple and rapid manner and was stable in both PBS and fetal bovine serum. It targeted selectively and could be taken up by tumor cells mainly via integrin αvβ3-receptor-mediated endocytosis. In vivo imaging, biodistribution, and autoradiography results showed evident tumor uptake in integrin αvβ3-expressing tumors. Conclusions. These promising results showed that this smart nanoprobe can be used for angiogenesis-targeted SPECT/CT imaging. Furthermore, the nanoprobe possesses a remarkable capacity for highly efficient photothermal conversion in the near-infrared region, suggesting its potential as a multifunctional theranostic agent.

A robust ligand exchange approach for preparing hydrophilic, biocompatible photoluminescent quantum dots

Energy Technology Data Exchange (ETDEWEB)

Wang, Sujuan; Zhou, Changhua [Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University, Kaifeng 475004 (China); Yuan, Hang [Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055 (China); Shen, Huaibin [Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University, Kaifeng 475004 (China); Zhao, Wenxiu [Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055 (China); Ma, Lan, E-mail: malan@sz.tsinghua.edu.cn [Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055 (China); Li, Lin Song, E-mail: lsli@henu.edu.cn [Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University, Kaifeng 475004 (China)

2013-08-01

Graphical abstract: - Highlights: • Aqueous CdSe/ZnS QDs were prepared using polymaleic anhydrides as capping ligand. • Effect of reaction temperature and time were systematically studied in the synthesis process. • Water-soluble QDs exhibited a good stability in physiological relevant environment. • The aqueous QDs were applied as biological probe to detect human embryonic stem cell. - Abstract: This paper describes a robust ligand exchange approach for preparing biocompatible CdSe/ZnS quantum dots (QDs) to make bioprobe for effective cell imaging. In this method, polymaleic anhydride (PMA) ligand are first used to replace original hydrophobic ligand (oleic acid) and form a protection shell with multiple hydrophilic groups to coat and protect CdSe/ZnS QDs. The as-prepared aqueous QDs exhibit small particle size, good colloidal stability in aqueous solutions with a wide range of pH, salt concentrations and under thermal treatment, which are necessary for biological applications. The use of this new class of aqueous QDs for effective cell imaging shows strong fluorescence signal to human embryonic stem cell, which demonstrate that PMA coated QDs are fully satisfied with the requirements of preparing high quality biological probe.

Imaging lysosomal highly reactive oxygen species and lighting up cancer cells and tumors enabled by a Si-rhodamine-based near-infrared fluorescent probe.

Science.gov (United States)

Zhang, Hongxing; Liu, Jing; Liu, Chenlu; Yu, Pengcheng; Sun, Minjia; Yan, Xiaohan; Guo, Jian-Ping; Guo, Wei

2017-07-01

Lysosomes have recently been regarded as the attractive pharmacological targets for selectively killing of cancer cells via lysosomal cell death (LCD) pathway that is closely associated with reactive oxygen species (ROS). However, the details on the ROS-induced LCD of cancer cells are still poorly understood, partially due to the absence of a lysosome-targetable, robust, and biocompatible imaging tool for ROS. In this work, we brought forward a Si-rhodamine-based fluorescent probe, named PSiR, which could selectively and sensitively image the pathologically more relavent highly reactive oxygen species (hROS: HClO, HO, and ONOO - ) in lysosomes of cancer cells. Compared with many of the existing hROS fluorescent probes, its superiorities are mainly embodied in the high stability against autoxidation and photoxidation, near-infrared exitation and emission, fast fluorescence off-on response, and specific lysosomal localization. Its practicality has been demonstrated by the real-time imaging of hROS generation in lysosomes of human non-small-cell lung cancer cells stimulated by anticancer drug β-lapachone. Moreover, the probe was sensitive enough for basal hROS in cancer cells, allowing its further imaging applications to discriminate not only cancer cells from normal cells, but also tumors from healthy tissues. Overall, our results strongly indicated that PSiR is a very promising imaging tool for the studies of ROS-related LCD of cancer cells, screening of new anticancer drugs, and early diagnosis of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

Science.gov (United States)

Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

2017-01-01

The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

Objective, Quantitative, Data-Driven Assessment of Chemical Probes.

Science.gov (United States)

Antolin, Albert A; Tym, Joseph E; Komianou, Angeliki; Collins, Ian; Workman, Paul; Al-Lazikani, Bissan

2018-02-15

Chemical probes are essential tools for understanding biological systems and for target validation, yet selecting probes for biomedical research is rarely based on objective assessment of all potential compounds. Here, we describe the Probe Miner: Chemical Probes Objective Assessment resource, capitalizing on the plethora of public medicinal chemistry data to empower quantitative, objective, data-driven evaluation of chemical probes. We assess >1.8 million compounds for their suitability as chemical tools against 2,220 human targets and dissect the biases and limitations encountered. Probe Miner represents a valuable resource to aid the identification of potential chemical probes, particularly when used alongside expert curation. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Biocompatibility of Different Nerve Tubes

Science.gov (United States)

Stang, Felix; Keilhoff, Gerburg; Fansa, Hisham

2009-01-01

Bridging nerve gaps with suitable grafts is a major clinical problem. The autologous nerve graft is considered to be the gold standard, providing the best functional results; however, donor site morbidity is still a major disadvantage. Various attempts have been made to overcome the problems of autologous nerve grafts with artificial nerve tubes, which are “ready-to-use” in almost every situation. A wide range of materials have been used in animal models but only few have been applied to date clinically, where biocompatibility is an inevitable prerequisite. This review gives an idea about artificial nerve tubes with special focus on their biocompatibility in animals and humans.

A novel three-input monomolecular logic circuit on a rhodamine inspired bio-compatible bi-compartmental molecular platform

International Nuclear Information System (INIS)

Mistri, Tarun; Bhowmick, Rahul; Katarkar, Atul; Chaudhuri, Keya; Ali, Mahammad

2017-01-01

Methodological synthesis of a new biocompatible bi-compartmental rhodamine based probe (L 3 ) provides a multi-inputs and multi-outputs molecular logic circuit based on simple chemosensing phenomena. Spectroscopic responses of Cu 2+ and Hg 2+ towards L 3 together with reversible binding of S 2- with L 3 -Cu 2+ and L 3 -Hg 2+ complexes help us to construct a thee-input molecular circuit on their control and sequential addition to a solution of L 3 in a mixed organo-aqueous medium. We have further successfully encoded binary digits out of these inputs and outputs which may convert a three-digit input string into a two-digit output string resulting a simple monomolecular logic circuit. Such a molecular ‘Boolean’ logic operation may improve the complexity of logic gate circuitry and computational speed and may be useful to employ in potential biocompatible molecular logic platforms. - Graphical abstract: A new bi-compartmental molecular system equipped with Rhodamine fluorophore unit provides a Multi-inputs and Multi-outputs Molecular Logic Circuit based on a very simple observation of chemosensing activities.

A hydrophobic organelle probe based on aggregation-induced emission: Nanosuspension preparation and direct use for endoplasmic reticulum imaging in living cells

Science.gov (United States)

Zheng, Sichao; Huang, Cuihong; Zhao, Xuyan; Zhang, Yong; Liu, Shuwen; Zhu, Qiuhua

2018-01-01

Organic fluorophores have a wide range of biological uses and are usually needed to be prepared as water-soluble compounds or nanoparticles for applications in aqueous biosystems owing to their hydrophobic properties, which often is a complex, time-consuming and high-cost process. Here, the nanoparticle preparation of hydrophobic fluorophores and their application in cell imaging have been investigated. It was found: a) fetal bovine serum (FBS) shows an excellent dispersion effect on hydrophobic small-molecule organic compounds; b) a hydrophobic C6-unsubstituted tetrahydropyrimidine (Me-THP-Naph) can be prepared as nanosuspensions utilizing cell culture medium with 10% FBS and directly be used as a specific real-time imaging probe for the endoplasmic reticulum (ER), a dynamic organelle playing a crucial role in many cellular processes. Compared with existing ER-targeted organic fluorescent probes, Me-THP-Naph, a product of an efficient five-component reaction that we developed, has unconventional aggregation-induced emission characteristics and shows advantages of low cost, long-term staining, good photostability, high signal-to-noise ratio and excellent biocompatibility, which make it a potential specific probe for real-time ER imaging. More importantly, this work affords a simple strategy for direct application of hydrophobic organic compounds in aqueous biological systems.

Multi probes measurements at the PALS Facility Research Centre during high intense laser pulse interactions with various target materials

Directory of Open Access Journals (Sweden)

De Marco Massimo

2018-01-01

Full Text Available During the interaction of high intense laser pulse with solid target, a large amount of hot electrons is produced and a giant Electromagnetic Pulse (EMP is generated due to the current flowing into the system target–target holder, as well as due to the escaping charged particles in vacuum. EMP production for different target materials is investigated inside and outside the target chamber, using monopole antenna, super wide-band microstrip antenna and Moebius antenna. The EMP consists in a fast transient magnetic field lasting hundreds of nanosecond with frequencies ranging from MHz to tens of GHz. Measurements of magnetic field and return target current in the range of kA were carried out by an inductive target probe (Cikhardt J. et al. Rev. Sci. Instrum. 85 (2014 103507.

Automated design of genomic Southern blot probes

Directory of Open Access Journals (Sweden)

Komiyama Noboru H

2010-01-01

Full Text Available Abstract Background Sothern blotting is a DNA analysis technique that has found widespread application in molecular biology. It has been used for gene discovery and mapping and has diagnostic and forensic applications, including mutation detection in patient samples and DNA fingerprinting in criminal investigations. Southern blotting has been employed as the definitive method for detecting transgene integration, and successful homologous recombination in gene targeting experiments. The technique employs a labeled DNA probe to detect a specific DNA sequence in a complex DNA sample that has been separated by restriction-digest and gel electrophoresis. Critically for the technique to succeed the probe must be unique to the target locus so as not to cross-hybridize to other endogenous DNA within the sample. Investigators routinely employ a manual approach to probe design. A genome browser is used to extract DNA sequence from the locus of interest, which is searched against the target genome using a BLAST-like tool. Ideally a single perfect match is obtained to the target, with little cross-reactivity caused by homologous DNA sequence present in the genome and/or repetitive and low-complexity elements in the candidate probe. This is a labor intensive process often requiring several attempts to find a suitable probe for laboratory testing. Results We have written an informatic pipeline to automatically design genomic Sothern blot probes that specifically attempts to optimize the resultant probe, employing a brute-force strategy of generating many candidate probes of acceptable length in the user-specified design window, searching all against the target genome, then scoring and ranking the candidates by uniqueness and repetitive DNA element content. Using these in silico measures we can automatically design probes that we predict to perform as well, or better, than our previous manual designs, while considerably reducing design time. We went on to

Corrosion and surface modification on biocompatible metals: A review.

Science.gov (United States)

Asri, R I M; Harun, W S W; Samykano, M; Lah, N A C; Ghani, S A C; Tarlochan, F; Raza, M R

2017-08-01

Corrosion prevention in biomaterials has become crucial particularly to overcome inflammation and allergic reactions caused by the biomaterials' implants towards the human body. When these metal implants contacted with fluidic environments such as bloodstream and tissue of the body, most of them became mutually highly antagonistic and subsequently promotes corrosion. Biocompatible implants are typically made up of metallic, ceramic, composite and polymers. The present paper specifically focuses on biocompatible metals which favorably used as implants such as 316L stainless steel, cobalt-chromium-molybdenum, pure titanium and titanium-based alloys. This article also takes a close look at the effect of corrosion towards the implant and human body and the mechanism to improve it. Due to this corrosion delinquent, several surface modification techniques have been used to improve the corrosion behavior of biocompatible metals such as deposition of the coating, development of passivation oxide layer and ion beam surface modification. Apart from that, surface texturing methods such as plasma spraying, chemical etching, blasting, electropolishing, and laser treatment which used to improve corrosion behavior are also discussed in detail. Introduction of surface modifications to biocompatible metals is considered as a "best solution" so far to enhanced corrosion resistance performance; besides achieving superior biocompatibility and promoting osseointegration of biocompatible metals and alloys. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of titanium incorporation on the structural, mechanical and biocompatible properties of DLC thin films prepared by reactive-biased target ion beam deposition method

International Nuclear Information System (INIS)

Bharathy, P. Vijai; Nataraj, D.; Chu, Paul K.; Wang, Huaiyu; Yang, Q.; Kiran, M.S.R.N.; Silvestre-Albero, J.; Mangalaraj, D.

2010-01-01

Amorphous diamond like carbon (DLC) and titanium incorporated diamond like carbon (Ti-DLC) thin films were deposited by using reactive-biased target ion beam deposition method. The effects of Ti incorporation and target bias voltage on the microstructure and mechanical properties of the as-deposited films were investigated by means of X-ray photoelectron spectroscopy, Raman spectroscopy, transmission electron microscopy and nano-indentation. It was found that the Ti content in Ti-DLC films gets increased with increasing target bias voltage. At about 4.2 at.% of Ti, uniform sized well dispersed nanocrystals were seen in the DLC matrix. Using FFT analysis, a facility available in the TEM, it was found that the nanocrystals are in cubic TiC phase. Though at the core, the incorporated Ti atoms react with carbon to form cubic TiC; most of the surface exposed Ti atoms were found to react with the atmospheric oxygen to form weakly bonded Ti-O. The presence of TiC nanocrystals greatly modified the sp 3 /sp 2 hybridized bonding ratio and is reflected in mechanical hardness of Ti-DLC films. These films were then tested for their biocompatibility by an invitro cell culturing test. Morphological observation and the cell proliferation test have demonstrated that the human osteoblast cells well attach and proliferate on the surface of Ti incorporated DLC films, suggesting possible applications in bone related implant coatings.

Limitation of biocompatibility of hydrated nanocrystalline hydroxyapatite

Science.gov (United States)

Minaychev, V. V.; Teleshev, A. T.; Gorshenev, V. N.; Yakovleva, M. A.; Fomichev, V. A.; Pankratov, A. S.; Menshikh, K. A.; Fadeev, R. S.; Fadeeva, I. S.; Senotov, A. S.; Kobyakova, M. I.; Yurasova, Yu B.; Akatov, V. S.

2018-04-01

Nanostructured hydroxyapatite (HA) in the form of hydrated paste is considered to be a promising material for a minor-invasive surgical curing of bone tissue injure. However questions about adhesion of cells on this material and its biocompatibility still remain. In this study biocompatibility of paste-formed nanosized HA (nano-HA) by in vitro methods is investigated. Nano-HA (particles sized about 20 nm) was synthesized under conditions of mechano-acoustic activation of an aqueous reaction mixture of ammonium hydrophosphate and calcium nitrate. It was ascertained that nanocrystalline paste was not cytotoxic although limitation of adhesion, spreading and growth of the cells on its surface was revealed. The results obtained point on the need of modification of hydrated nano-HA in the aims of increasing its biocompatibility and osteoplastic potential.

Nanodiamonds and silicon quantum dots: ultrastable and biocompatible luminescent nanoprobes for long-term bioimaging.

Science.gov (United States)

Montalti, M; Cantelli, A; Battistelli, G

2015-07-21

Fluorescence bioimaging is a powerful, versatile, method for investigating, both in vivo and in vitro, the complex structures and functions of living organisms in real time and space, also using super-resolution techniques. Being poorly invasive, fluorescence bioimaging is suitable for long-term observation of biological processes. Long-term detection is partially prevented by photobleaching of organic fluorescent probes. Semiconductor quantum dots, in contrast, are ultrastable, fluorescent contrast agents detectable even at the single nanoparticle level. Emission color of quantum dots is size dependent and nanoprobes emitting in the near infrared (NIR) region are ideal for low back-ground in vivo imaging. Biocompatibility of nanoparticles, containing toxic elements, is debated. Recent safety concerns enforced the search for alternative ultrastable luminescent nanoprobes. Most recent results demonstrated that optimized silicon quantum dots (Si QDs) and fluorescent nanodiamonds (FNDs) show almost no photobleaching in a physiological environment. Moreover in vitro and in vivo toxicity studies demonstrated their unique biocompatibility. Si QDs and FNDs are hence ideal diagnostic tools and promising non-toxic vectors for the delivery of therapeutic cargos. Most relevant examples of applications of Si QDs and FNDs to long-term bioimaging are discussed in this review comparing the toxicity and the stability of different nanoprobes.

Probe Selection for DNA Microarrays using OligoWiz

DEFF Research Database (Denmark)

Wernersson, Rasmus; Juncker, Agnieszka; Nielsen, Henrik Bjørn

2007-01-01

Nucleotide abundance measurements using DNA microarray technology are possible only if appropriate probes complementary to the target nucleotides can be identified. Here we present a protocol for selecting DNA probes for microarrays using the OligoWiz application. OligoWiz is a client-server appl......Nucleotide abundance measurements using DNA microarray technology are possible only if appropriate probes complementary to the target nucleotides can be identified. Here we present a protocol for selecting DNA probes for microarrays using the OligoWiz application. OligoWiz is a client......-server application that offers a detailed graphical interface and real-time user interaction on the client side, and massive computer power and a large collection of species databases (400, summer 2007) on the server side. Probes are selected according to five weighted scores: cross-hybridization, deltaT(m), folding...... computer skills and can be executed from any Internet-connected computer. The probe selection procedure for a standard microarray design targeting all yeast transcripts can be completed in 1 h....

Microfabrication of biocompatible hydrogels by proton beam writing

Science.gov (United States)

Nagasawa, Naotsugu; Kimura, Atsushi; Idesaki, Akira; Yamada, Naoto; Koka, Masashi; Satoh, Takahiro; Ishii, Yasuyuki; Taguchi, Mitsumasa

2017-10-01

Functionalization of biocompatible materials is expected to be widely applied in biomedical engineering and regenerative medicine fields. Hydrogel has been expected as a biocompatible scaffold which support to keep an organ shape during cell multiplying in regenerative medicine. Therefore, it is important to understanding a surface microstructure (minute shape, depth of flute) and a chemical characteristic of the hydrogel affecting the cell culture. Here, we investigate the microfabrication of biocompatible polymeric materials, such as the water-soluble polysaccharide derivatives hydroxypropyl cellulose and carboxymethyl cellulose, by use of proton beam writing (PBW). These polymeric materials were dissolved thoroughly in pure water using a planetary centrifugal mixer, and a sample sheet (1 mm thick) was formed on polyethylene terephthalate (PET) film. Crosslinking to form hydrogels was induced using a 3.0 MeV focused proton beam from the single-ended accelerator at Takasaki Ion Accelerators for Advanced Radiation Application. The aqueous samples were horizontally irradiated with the proton beam through the PET cover film, and then rinsed with deionized water. Microstructured hydrogels were obtained on the PET film using the PBW technique without toxic crosslinking reagents. Cell adhesion and proliferation on the microfabricated biocompatible hydrogels were investigated. Microfabrication of HPC and CMC by the use of PBW is expected to produce new biocompatible materials that can be applied in biological and medical applications.

Interface-Targeting Strategy Enables Two-Photon Fluorescent Lipid Droplet Probes for High-Fidelity Imaging of Turbid Tissues and Detecting Fatty Liver.

Science.gov (United States)

Guo, Lifang; Tian, Minggang; Feng, Ruiqing; Zhang, Ge; Zhang, Ruoyao; Li, Xuechen; Liu, Zhiqiang; He, Xiuquan; Sun, Jing Zhi; Yu, Xiaoqiang

2018-04-04

Lipid droplets (LDs) with unique interfacial architecture not only play crucial roles in protecting a cell from lipotoxicity and lipoapoptosis but also closely relate with many diseases such as fatty liver and diabetes. Thus, as one of the important applied biomaterials, fluorescent probes with ultrahigh selectivity for in situ and high-fidelity imaging of LDs in living cells and tissues are critical to elucidate relevant physiological and pathological events as well as detect related diseases. However, available probes only utilizing LDs' waterless neutral cores but ignoring the unique phospholipid monolayer interfaces exhibit low selectivity. They cannot differentiate neutral cores of LDs from intracellular other lipophilic microenvironments, which results in extensively cloud-like background noise and severely limited their bioapplications. Herein, to design LD probes with ultrahigh selectivity, the exceptional interfacial architecture of LDs is considered adequately and thus an interface-targeting strategy is proposed for the first time. According to the novel strategy, we have developed two amphipathic fluorescent probes (N-Cy and N-Py) by introducing different cations into a lipophilic fluorophore (nitrobenzoxadiazole (NBD)). Consequently, their cationic moiety precisely locates the interfaces through electrostatic interaction and simultaneously NBD entirely embeds into the waterless core via hydrophobic interaction. Thus, high-fidelity and background-free fluorescence imaging of LDs are expectably realized in living cells in situ. Moreover, LDs in turbid tissues like skeletal muscle slices have been clearly imaged (up to 82 μm depth) by a two-photon microscope. Importantly, using N-Cy, we not only intuitively monitored the variations of LDs in number, size, and morphology but also clearly revealed their abnormity in hepatic tissues resulting from fatty liver. Therefore, these unique probes provide excellent imaging tools for elucidating LD

Polysaccharide-based Noncovalent Assembly for Targeted Delivery of Taxol

Science.gov (United States)

Yang, Yang; Zhang, Ying-Ming; Chen, Yong; Chen, Jia-Tong; Liu, Yu

2016-01-01

The construction of synthetic straightforward, biocompatible and biodegradable targeted drug delivery system with fluorescent tracking abilities, high anticancer activities and low side effects is still a challenge in the field of biochemistry and material chemistry. In this work, we constructed targeted paclitaxel (Taxol) delivery nanoparticles composed of permethyl-β-cyclodextrin modified hyaluronic acid (HApCD) and porphyrin modified paclitaxel prodrug (PorTaxol), through host-guest and amphiphilic interactions. The obtained nanoparticles (HATXP) were biocompatible and enzymatic biodegradable due to their hydrophilic hyaluronic acid (HA) shell and hydrophobic Taxol core, and exhibited specific targeting internalization into cancer cells via HA receptor mediated endocytosis effects. The cytotoxicity experiments showed that the HATXP exhibited similar anticancer activities to, but much lower side effects than commercial anticancer drug Taxol. The present work would provide a platform for targeted paclitaxel drug delivery and a general protocol for the design of advanced multifunctional nanoscale biomaterials for targeted drug/gene delivery.

Biocompatible and colloidally stabilized mPEG-PE/calcium phosphate hybrid nanoparticles loaded with siRNAs targeting tumors

OpenAIRE

Gao, Pei; Zhang, Xiangyu; Wang, Hongzhi; Zhang, Qinghong; Li, He; Li, Yaogang; Duan, Yourong

2015-01-01

Calcium phosphate nanoparticles are safe and effective delivery vehicles for small interfering RNA (siRNA), as a result of their excellent biocompatibility. In this work, mPEG-PE (polyethylene glycol-L-?-phosphatidylethanolamine) was synthesized and used to prepare nanoparticles composed of mPEG-PE and calcium phosphate for siRNA delivery. Calcium phosphate and mPEG-PE formed the stable hybrid nanoparticles through self-assembly resulting from electrostatic interaction in water. The average s...

Overview of Stabilizing Ligands for Biocompatible Quantum Dot Nanocrystals

Directory of Open Access Journals (Sweden)

Aaron Clapp

2011-11-01

Full Text Available Luminescent colloidal quantum dots (QDs possess numerous advantages as fluorophores in biological applications. However, a principal challenge is how to retain the desirable optical properties of quantum dots in aqueous media while maintaining biocompatibility. Because QD photophysical properties are directly related to surface states, it is critical to control the surface chemistry that renders QDs biocompatible while maintaining electronic passivation. For more than a decade, investigators have used diverse strategies for altering the QD surface. This review summarizes the most successful approaches for preparing biocompatible QDs using various chemical ligands.

A capillary viscometer designed for the characterization of biocompatible ferrofluids

Energy Technology Data Exchange (ETDEWEB)

Nowak, J., E-mail: johannes.nowak@tu-dresden.de; Odenbach, S.

2016-08-01

Suspensions of magnetic nanoparticles are receiving a growing interest in biomedical research. These ferrofluids can, e.g., be used for the treatment of cancer, making use of the drug targeting principle or using an artificially induced heating. To enable a safe application the basic properties of the ferrofluids have to be well understood, including the viscosity of the fluids if an external magnetic field is applied. It is well known that the viscosity of ferrofluids rises if a magnetic field is applied, where the rise depends on shear rate and magnetic field strength. In case of biocompatible ferrofluids such investigations proved to be rather complicated as the experimental setup should be close to the actual application to allow justified predictions of the effects which have to be expected. Thus a capillary viscometer, providing a flow situation comparable to the flow in a blood vessel, has been designed. The glass capillary is exchangeable and different inner diameters can be used. The range of the shear rates has been adapted to the range found in the human organism. The application of an external magnetic field is enabled with two different coil setups covering the ranges of magnetic field strengths required on the one hand for a theoretical understanding of particle interaction and resulting changes in viscosity and on the other hand for values necessary for a potential biomedical application. The results show that the newly designed capillary viscometer is suitable to measure the magnetoviscous effect in biocompatible ferrofluids and that the results appear to be consistent with data measured with rotational rheometry. In addition, a strong change of the flow behaviour of a biocompatible ferrofluid was proven for ranges of the shear rate and the magnetic field strength expected for a potential biomedical application. - Highlights: • A capillary viscometer to characterize biocompatible ferrofluids is presented. • Shear rates and capillary diameters

Science and technology of biocompatible thin films for implantable biomedical devices.

Energy Technology Data Exchange (ETDEWEB)

Li, W.; Kabius, B.; Auciello, O.; Materials Science Division

2010-01-01

This presentation focuses on reviewing research to develop two critical biocompatible film technologies to enable implantable biomedical devices, namely: (1) development of bioinert/biocompatible coatings for encapsulation of Si chips implantable in the human body (e.g., retinal prosthesis implantable in the human eye) - the coating involves a novel ultrananocrystalline diamond (UNCD) film or hybrid biocompatible oxide/UNCD layered films; and (2) development of biocompatible films with high-dielectric constant and microfabrication process to produce energy storage super-capacitors embedded in the microchip to achieve full miniaturization for implantation into the human body.

Exciton-controlled fluorescence: application to hybridization-sensitive fluorescent DNA probe.

Science.gov (United States)

Okamoto, Akimitsu; Ikeda, Shuji; Kubota, Takeshi; Yuki, Mizue; Yanagisawa, Hiroyuki

2009-01-01

A hybridization-sensitive fluorescent probe has been designed for nucleic acid detection, using the concept of fluorescence quenching caused by the intramolecular excitonic interaction of fluorescence dyes. We synthesized a doubly thiazole orange-labeled nucleotide showing high fluorescence intensity for a hybrid with the target nucleic acid and effective quenching for the single-stranded state. This exciton-controlled fluorescent probe was applied to living HeLa cells using microinjection to visualize intracellular mRNA localization. Immediately after injection of the probe into the cell, fluorescence was observed from the probe hybridizing with the target RNA. This fluorescence rapidly decreased upon addition of a competitor DNA. Multicoloring of this probe resulted in the simple simultaneous detection of plural target nucleic acid sequences. This probe realized a large, rapid, reversible change in fluorescence intensity in sensitive response to the amount of target nucleic acid, and facilitated spatiotemporal monitoring of the behavior of intracellular RNA.

In situ detection of denitrifying bacteria by mRNA-targeted nucleic acid probes and catalyzed reporter deposition

DEFF Research Database (Denmark)

Kofoed, Michael Vedel; Stief, Peter; Poulsen, Morten

can be designed to target a broader range of denitrifying bacteria; however, they require two-pass CARD-FISH, which may result in (too) high background fluorescence. In a first application example, habitat-specific polynucleotide probes were used to quantify bacteria expressing narG and nos...... reduction of nitrate to dinitrogen gas, is essential for the removal of fixed nitrogen from natural and engineered ecosystems. However, community structure and activity dynamics of denitrifying bacteria in most systems are poorly understood, partially due to difficulties in identifying and quantifying...... and catalyzed fluorescent reporter deposition (CARD-FISH). The general feasibility of the approach was first tested with pure cultures of Pseudomonas stutzeri and various denitrifying and nitrate-reducing isolates. Detailed studies of probe specificity and hybridization conditions using Clone-FISH of nar...

Novel biocompatible hydrogel nanoparticles: generation and size-tuning of nanoparticles by the formation of micelle templates obtained from thermo-responsive monomers mixtures

Energy Technology Data Exchange (ETDEWEB)

Khandadash, Raz; Machtey, Victoria [Bar Ilan University, Department of Chemistry (Israel); Shainer, Inbal [Tel-Aviv University, Department of Neurobiology, The George S. Wise Faculty of Life Sciences (Israel); Gottlieb, Hugo E. [Bar Ilan University, Department of Chemistry (Israel); Gothilf, Yoav [Tel-Aviv University, Department of Neurobiology, The George S. Wise Faculty of Life Sciences, and Sagol School of Neuroscience (Israel); Ebenstein, Yuval [Tel Aviv University, Raymond and Beverly Sackler Faculty of Exact Sciences, School of Chemistry (Israel); Weiss, Aryeh [Bar Ilan University, School of Engineering (Israel); Byk, Gerardo, E-mail: gerardo.byk@biu.ac.il [Bar Ilan University, Department of Chemistry (Israel)

2014-12-15

Biocompatible hydrogel nanoparticles are prepared by polymerization and cross-linking of N-isopropyl acrylamide in a micelle template formed by block copolymers macro-monomers at high temperature. Different monomer ratios form, at high temperature, well-defined micelles of different sizes which are further polymerized leading to nanoparticles with varied sizes from 20 to 390 nm. Physico-chemical characterization of the nanoparticles demonstrates their composition and homogeneity. The NPs were tested in vitro and in vivo biocompatibility assays, and their lack of toxicity was proven. The NPs can be labeled with fluorescent probes, and their intracellular fate can be visualized and quantified using confocal microscopy. Their uptake by live stem cells and distribution in whole developing animals is reported. On the basis of our results, a mechanism of nanoparticle formation is suggested. The lack of toxicity makes these nanoparticles especially attractive for biological applications such as screening and bio-sensing.

Ion implantation and bio-compatibility

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Yoshiaki; Kusakabe, Masahiro [Sony Corp., Tokyo (Japan). Corporate Research Labs.; Iwaki, Masaya

1992-07-01

Surface modification of polymers by ion implantation has been carried out to control surface properties such as conductivity, wettability, blood and tissue compatibility. Ion implantation into silicone rubber, polystyrene and segmented polyurethane was performed at 150 keV with doses ranging from 1 x 10[sup 15] to 3 x 10[sup 17] ions/cm[sup 2] to improve bio-compatibility. The platelet accumulation on ion implanted silicone rubber decreased and non-thrombogenicity of ion implanted specimens were improved. The ion implanted polystyrene and segmented polyurethane have been found to exhibit remarkably higher adhesion and spreading of endothelial cells compared to the non-implanted case. It is concluded that ion implantation into polymers is effective in controlling their bio-compatibility. (author).

Biocompatible polysaccharide-based cryogels

Energy Technology Data Exchange (ETDEWEB)

Reichelt, Senta, E-mail: senta.reichelt@iom-leipzig.de [Leibniz Institute of Surface Modification, Permoserstr. 15, 04318 Leipzig (Germany); Becher, Jana; Weisser, Jürgen [Innovent e.V., Pruessingstr. 27B, 07745 Jena (Germany); Prager, Andrea; Decker, Ulrich [Leibniz Institute of Surface Modification, Permoserstr. 15, 04318 Leipzig (Germany); Möller, Stephanie; Berg, Albrecht; Schnabelrauch, Matthias [Innovent e.V., Pruessingstr. 27B, 07745 Jena (Germany)

2014-02-01

This study focuses on the development of novel biocompatible macroporous cryogels by electron-beam assisted free-radical crosslinking reaction of polymerizable dextran and hyaluronan derivatives. As a main advantage this straightforward approach provides highly pure materials of high porosity without using additional crosslinkers or initiators. The cryogels were characterized with regard to their morphology and their basic properties including thermal and mechanical characteristics, and swellability. It was found that the applied irradiation dose and the chemical composition strongly influence the material properties of the resulting cryogels. Preliminary cytotoxicity tests illustrate the excellent in vitro-cytocompatibility of the fabricated cryogels making them especially attractive as matrices in tissue regeneration procedures. - Graphical abstract: Electron-beam initiated synthesis of biocompatible cryogels based on natural polymers. - Highlights: • Successful electron-beam induced synthesis of dextran and hyaluronan cryogels. • Mechanical and thermal stable cryogels were obtained. • Excellent cytocompatibility of the materials was proven. • Promising materials for tissue engineering were developed.

Synovitis in mice with inflammatory arthritis monitored with quantitative analysis of dynamic contrast-enhanced NIR fluorescence imaging using iRGD-targeted liposomes as fluorescence probes

Directory of Open Access Journals (Sweden)

Wu H

2018-03-01

Full Text Available Hao Wu,1,2,* Haohan Wu,1,2,* Yanni He,1 Zhen Gan,2 Zhili Xu,1,2 Meijun Zhou,1,2 Sai Liu,1,2 Hongmei Liu1 1Department of Ultrasonography, Guangdong Second Provincial General Hospital Affiliated to Southern Medical University, Guangzhou, China; 2Department of Ultrasonography, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China *These authors contributed equally to this work Background: Rheumatoid arthritis (RA is a common inflammatory disorder characterized primarily by synovitis and pannus formation in multiple joints, causing joints destruction and irreversible disability in most cases. Early diagnosis and effective therapy monitoring of RA are of importance for achieving the favorable prognosis. Methods: We first prepared the targeted fluorescence probes, and then explored the feasibility of near-infrared (NIR fluorescence molecular imaging to detect and evaluate the RA via the targeted fluorescence probes by quantitative analysis in this study. Results: The targeted fluorescence probes (indocyanine green-liposomes decorated with iRGD peptide [iLPs] was successfully prepared. The quantitative analysis found that strong fluorescence signal was detected in inflamed paws and the fluorescence signal in iLPs group was 3.03-fold higher than that in non-targeted (indocyanine green-liposomes decorated without iRGD peptide [LPs] group (P<0.01 at 15 min after injection, whereas the fluorescence signal from iLPs signal can almost not be observed in the non-inflamed paws, showing the high sensitivity and accuracy for arthritis by the NIR fluorescence imaging based on iLPs. Conclusion: The NIR fluorescence imaging by iLPs may facilitate improved arthritis diagnosis and early assessment of the disease progression by providing an in vivo characterization of angiogenesis in inflammatory joint diseases. Keywords: rheumatoid arthritis, synovitis, diagnosis, near-infrared fluorescence imaging, iRGD-targeted probes

Effect of titanium incorporation on the structural, mechanical and biocompatible properties of DLC thin films prepared by reactive-biased target ion beam deposition method

Energy Technology Data Exchange (ETDEWEB)

Bharathy, P. Vijai [Thin Films and Nanomaterials Lab, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Department of Mechanical Engineering, University of Saskatchewan, Saskatoon (Canada); Nataraj, D., E-mail: de.natraj@gmail.com [Thin Films and Nanomaterials Lab, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India); Chu, Paul K.; Wang, Huaiyu [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon (Hong Kong); Yang, Q. [Department of Mechanical Engineering, University of Saskatchewan, Saskatoon (Canada); Kiran, M.S.R.N. [School of Physics, University of Hyderabad, Hyderabad, Andra Pradesh (India); Silvestre-Albero, J. [Laboratorio de Materiales Avanzados, Departmento de Quimica Inorganica, Universidad de Alicante, Ap 99, E-03080 Alicante (Spain); Mangalaraj, D. [Thin Films and Nanomaterials Lab, School of Physical Sciences, Bharathiar University, Coimbatore 641046 (India)

2010-10-15

Amorphous diamond like carbon (DLC) and titanium incorporated diamond like carbon (Ti-DLC) thin films were deposited by using reactive-biased target ion beam deposition method. The effects of Ti incorporation and target bias voltage on the microstructure and mechanical properties of the as-deposited films were investigated by means of X-ray photoelectron spectroscopy, Raman spectroscopy, transmission electron microscopy and nano-indentation. It was found that the Ti content in Ti-DLC films gets increased with increasing target bias voltage. At about 4.2 at.% of Ti, uniform sized well dispersed nanocrystals were seen in the DLC matrix. Using FFT analysis, a facility available in the TEM, it was found that the nanocrystals are in cubic TiC phase. Though at the core, the incorporated Ti atoms react with carbon to form cubic TiC; most of the surface exposed Ti atoms were found to react with the atmospheric oxygen to form weakly bonded Ti-O. The presence of TiC nanocrystals greatly modified the sp{sup 3}/sp{sup 2} hybridized bonding ratio and is reflected in mechanical hardness of Ti-DLC films. These films were then tested for their biocompatibility by an invitro cell culturing test. Morphological observation and the cell proliferation test have demonstrated that the human osteoblast cells well attach and proliferate on the surface of Ti incorporated DLC films, suggesting possible applications in bone related implant coatings.

Development of a 16S rRNA-targeted fluorescence in situ hybridization probe for quantification of the ammonia-oxidizer Nitrosotalea devanaterra and its relatives.

Science.gov (United States)

Restrepo-Ortiz, C X; Merbt, S N; Barrero-Canossa, J; Fuchs, B M; Casamayor, E O

2018-04-28

The Thaumarchaeota SAGMCG-1 group and, in particular, members of the genus Nitrosotalea have high occurrence in acidic soils, the rhizosphere, groundwater and oligotrophic lakes, and play a potential role in nitrogen cycling. In this study, the specific oligonucleotide fluorescence in situ hybridization probe SAG357 was designed for this Thaumarchaeota group based on the available 16S rRNA gene sequences in databases, and included the ammonia-oxidizing species Nitrosotalea devanaterra. Cell permeabilization for catalyzed reporter deposition fluorescence in situ detection and the hybridization conditions were optimized on enrichment cultures of the target species N. devanaterra, as well as the non-target ammonia-oxidizing archaeon Nitrosopumilus maritimus. Probe specificity was improved with a competitor oligonucleotide, and fluorescence intensity and cell visualization were enhanced by the design and application of two adjacent helpers. Probe performance was tested in soil samples along a pH gradient, and counting results matched the expected in situ distributions. Probe SAG357 and the CARD-FISH protocol developed in the present study will help to improve the current understanding of the ecology and physiology of N. devanaterra and its relatives in natural environments. Copyright © 2018 Elsevier GmbH. All rights reserved.

Miniature probe for the delivery and monitoring of a photopolymerizable material

Science.gov (United States)

Schmocker, Andreas; Khoushabi, Azadeh; Schizas, Constantin; Bourban, Pierre-Etienne; Pioletti, Dominique P.; Moser, Christophe

2015-12-01

Photopolymerization is a common method to cure materials initially in a liquid state, such as dental implants or bone or tissue fillers. Recent advances in the development of biocompatible gel- and cement-systems open up an avenue for in situ photopolymerization. For minimally invasive surgery, such procedures require miniaturized surgical endoscopic probes to activate and control photopolymerization in situ. We present a miniaturized light probe in which a photoactive material can be (1) mixed, pressurized, and injected, (2) photopolymerized/photoactivated, and (3) monitored during the chemical reaction. The device is used to implant and cure poly(ethylene glycol) dimethacrylate-hydrogel-precursor in situ with ultraviolet A (UVA) light (365 nm) while the polymerization reaction is monitored in real time by collecting the fluorescence and Raman signals generated by the 532-nm excitation light source. Hydrogels could be delivered, photopolymerized, and monitored by the probe up to a curing depth of 4 cm. The size of the photopolymerized samples could be correlated to the fluorescent signal collected by the probe, and the reproducibility of the procedure could be demonstrated. The position of the probe tip inside a bovine caudal intervertebral disc could be estimated in vitro based on the collected fluorescence and Raman signal.

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.

A novel three-input monomolecular logic circuit on a rhodamine inspired bio-compatible bi-compartmental molecular platform

Energy Technology Data Exchange (ETDEWEB)

Mistri, Tarun; Bhowmick, Rahul [Department of Chemistry, Jadavpur University, 188 Raja S.C. Mullick Road, Kolkata 700032 (India); Katarkar, Atul; Chaudhuri, Keya [Molecular & Human Genetics Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata 700032 (India); Ali, Mahammad, E-mail: mali@chemistry.jdvu.ac.in [Department of Chemistry, Jadavpur University, 188 Raja S.C. Mullick Road, Kolkata 700032 (India)

2017-05-15

Methodological synthesis of a new biocompatible bi-compartmental rhodamine based probe (L{sup 3}) provides a multi-inputs and multi-outputs molecular logic circuit based on simple chemosensing phenomena. Spectroscopic responses of Cu{sup 2+} and Hg{sup 2+} towards L{sup 3} together with reversible binding of S{sup 2-} with L{sup 3}-Cu{sup 2+} and L{sup 3}-Hg{sup 2+} complexes help us to construct a thee-input molecular circuit on their control and sequential addition to a solution of L{sup 3} in a mixed organo-aqueous medium. We have further successfully encoded binary digits out of these inputs and outputs which may convert a three-digit input string into a two-digit output string resulting a simple monomolecular logic circuit. Such a molecular ‘Boolean’ logic operation may improve the complexity of logic gate circuitry and computational speed and may be useful to employ in potential biocompatible molecular logic platforms. - Graphical abstract: A new bi-compartmental molecular system equipped with Rhodamine fluorophore unit provides a Multi-inputs and Multi-outputs Molecular Logic Circuit based on a very simple observation of chemosensing activities.

A novel mitochondria-targeted two-photon fluorescent probe for dynamic and reversible detection of the redox cycles between peroxynitrite and glutathione.

Science.gov (United States)

Sun, Chunlong; Du, Wen; Wang, Peng; Wu, Yang; Wang, Baoqin; Wang, Jun; Xie, Wenjun

2017-12-16

Redox homeostasis is important for maintenance of normal physiological functions within cells. Redox state of cells is primarily a consequence of precise balance between levels of reducing equivalents and reactive oxygen species. Redox homeostasis between peroxynitrite (ONOO - ) and glutathione (GSH) is closely associated with physiological and pathological processes, such as prolonged relaxation in vascular tissues and smooth muscle preparations, attenuation of hepatic necrosis, and activation of matrix metalloproteinase-2. We report a two-photon fluorescent probe (TP-Se) based on water-soluble carbazole-based compound, which integrates with organic selenium, to monitor changes in ONOO - /GSH levels in cells. This probe can reversibly respond to ONOO - and GSH and exhibits high selectivity, sensitivity, and mitochondrial targeting. The probe was successfully applied to visualize changes in redox cycles during ONOO - outbreak and antioxidant GSH repair in cells. The probe will lead to significant development on redox events involved in cellular redox regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Progresses in optimization strategy for radiolabeled molecular probes targeting integrin αvβ3

International Nuclear Information System (INIS)

Chen Haojun; Wu Hua

2012-01-01

Tumor angiogenesis is critical in the growth, invasion and metastasis of malignant tumors. The integrins, which express on many types of tumor cells and activated vascular endothelial cells, play an important role in regulation of the tumor angiogenesis. RGD peptide, which contains Arg-Gly-Asp sequence, binds specifically to integrin α v β 3 . Therefore, the radiolabeled RGD peptides may have broad application prospects in radionuclide imaging and therapy. Major research interests include the selection of radionuclides, modification and improvement of RGD structures. In this article, we give a review on research progresses in optimization strategy for radiolabeled molecular probes targeting integrin α v β 3 . (authors)

Atomic Force Microscopy Probing of Receptor–Nanoparticle Interactions for Riboflavin Receptor Targeted Gold–Dendrimer Nanocomposites

Science.gov (United States)

2015-01-01

Riboflavin receptors are overexpressed in malignant cells from certain human breast and prostate cancers, and they constitute a group of potential surface markers important for cancer targeted delivery of therapeutic agents and imaging molecules. Here we report on the fabrication and atomic force microscopy (AFM) characterization of a core–shell nanocomposite consisting of a gold nanoparticle (AuNP) coated with riboflavin receptor-targeting poly(amido amine) dendrimer. We designed this nanocomposite for potential applications such as a cancer targeted imaging material based on its surface plasmon resonance properties conferred by AuNP. We employed AFM as a technique for probing the binding interaction between the nanocomposite and riboflavin binding protein (RfBP) in solution. AFM enabled precise measurement of the AuNP height distribution before (13.5 nm) and after chemisorption of riboflavin-conjugated dendrimer (AuNP–dendrimer; 20.5 nm). Binding of RfBP to the AuNP–dendrimer caused a height increase to 26.7 nm, which decreased to 22.8 nm when coincubated with riboflavin as a competitive ligand, supporting interaction of AuNP–dendrimer and its target protein. In summary, physical determination of size distribution by AFM imaging can serve as a quantitative approach to monitor and characterize the nanoscale interaction between a dendrimer-covered AuNP and target protein molecules in vitro. PMID:24571134

Bioresponsive probes for molecular imaging:Concepts and in vivo applications

OpenAIRE

Duijnhoven, van, SMJ Sander; Robillard, MS Marc; Langereis, S Sander; Grüll, H Holger

2015-01-01

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of molecular imaging probes, known as bioresponsive molecular probes, has been developed. These probes generally benefit from signal enhancement at the site of interaction with its target. There are mainly ...

Unlabeled probes for the detection and typing of herpes simplex virus.

Science.gov (United States)

Dames, Shale; Pattison, David C; Bromley, L Kathryn; Wittwer, Carl T; Voelkerding, Karl V

2007-10-01

Unlabeled probe detection with a double-stranded DNA (dsDNA) binding dye is one method to detect and confirm target amplification after PCR. Unlabeled probes and amplicon melting have been used to detect small deletions and single-nucleotide polymorphisms in assays where template is in abundance. Unlabeled probes have not been applied to low-level target detection, however. Herpes simplex virus (HSV) was chosen as a model to compare the unlabeled probe method to an in-house reference assay using dual-labeled, minor groove binding probes. A saturating dsDNA dye (LCGreen Plus) was used for real-time PCR. HSV-1, HSV-2, and an internal control were differentiated by PCR amplicon and unlabeled probe melting analysis after PCR. The unlabeled probe technique displayed 98% concordance with the reference assay for the detection of HSV from a variety of archived clinical samples (n = 182). HSV typing using unlabeled probes was 99% concordant (n = 104) to sequenced clinical samples and allowed for the detection of sequence polymorphisms in the amplicon and under the probe. Unlabeled probes and amplicon melting can be used to detect and genotype as few as 10 copies of target per reaction, restricted only by stochastic limitations. The use of unlabeled probes provides an attractive alternative to conventional fluorescence-labeled, probe-based assays for genotyping and detection of HSV and might be useful for other low-copy targets where typing is informative.

Biocompatible nanogel derived from functionalized dextrin for targeted delivery of doxorubicin hydrochloride to MG 63 cancer cells.

Science.gov (United States)

Das, Dipankar; Rameshbabu, Arun Prabhu; Ghosh, Paulomi; Patra, Priyapratim; Dhara, Santanu; Pal, Sagar

2017-09-01

The present article demonstrates the targeted delivery of doxorubicin hydrochloride to human osteosarcoma cancer cell lines (MG 63) using functionalized dextrin based crosslinked, pH responsive and biocompatible nanogel. The nanogel has been prepared through Michael-type addition reaction using dextrin (Dxt), N, N'-methylene bisacrylamide (MBA, as crosslinker), acrylic acid (AA, as monomer) and potassium persulfate (KPS, as initiator). The structure, composition, morphology of the nanogel have been explored using FTIR and 1 H NMR spectroscopy, XRD, TGA, DSC, CHN and AFM analyses. The TEM analysis confirmed that the size of nanogel appeared within 100nm, while DLS study indicates that the diameter of the nanogel remained between 113 and 126nm. The AFM study implied the porous morphology of the synthesized nanogel. The rheological study suggests the gel behaviour of the synthesized nanogel at 37±0.1°C. Difference in% swelling at pH 5.5 and 7.4 indicates pH-responsiveness of the nanogel. The in vitro cytocompatibility results ascertained that the nanogel is non-toxic to human mesenchymal stem cells (hMSCs). In vitro cellular uptake study confirmed that FITC-loaded nanogel can cross the cellular membrane and be well uptake by the cell cytoplasm. The nanogel could efficiently encapsulate doxorubicin hydrochloride (Dox) with the loading efficiency of 27±0.2% after 72h. The Dox-loaded nanogel demonstrates anti-cancer activity towards MG 63 cancer cells and release the encapsulated drug in a controlled way. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lipid-Polymer Nanoparticles for Folate-Receptor Targeting Delivery of Doxorubicin.

Science.gov (United States)

Zheng, Mingbin; Gong, Ping; Zheng, Cuifang; Zhao, Pengfei; Luo, Zhenyu; Ma, Yifan; Cai, Lintao

2015-07-01

A biocompatible PLGA-lipid hybrid nanoparticles (NPs) was developed for targeted delivery of anticancer drugs with doxorubicin (DOX). The hydrodynamic diameter and zeta potential of DOX-loaded PLGA-lipid NPs (DNPs) were affected by the mass ratio of Lipid/PLGA or DSPE-PEG-COOH/Lecithin. At the 1:20 drug/polymer mass ratio, the mean hydrodynamic diameter of DNPs was the lowest (99.2 1.83 nm) and the NPs presented the encapsulation efficiency of DOX with 42.69 1.30%. Due to the folate-receptor mediated endocytosis, the PLGA-lipid NPs with folic acid (FA) targeting ligand showed significant higher uptake by folate-receptor-positive MCF-7 cells as compared to PLGA-lipid NPs without folate. Confocal microscopic observation and flow cytometry analysis also supported the enhanced cellular uptake of the FA-targeted NPs. The results indicated that the FA-targeted DNPs exhibited higher cytotoxicity in MCF-7 cells compared with non-targeted NPs. The lipid-polymer nanoparticles provide a solution of biocompatible nanocarrier for cancer targeting therapy.

16S rRNA-targeted probes for specific detection of Thermoanaerobacterium spp., Thermoanaerobacterium thermosaccharolyticum, and Caldicellulosiruptor spp. by fluorescent in situ hybridization in biohydrogen producing systems

Energy Technology Data Exchange (ETDEWEB)

O-Thong, Sompong [Department of Environmental Engineering, Technical University of Denmark, Bygningstorvet Bg 115, DK-2800, Kgs Lyngby (Denmark); Department of Biology, Faculty of Science, Thaksin University, Patthalung 93110 (Thailand); Prasertsan, Poonsuk [Department of Industrial Biotechnology, Faculty of Agro-Industry, Prince of Songkla University, Hat-Yai, Songkhla 90112 (Thailand); Karakashev, Dimitar; Angelidaki, Irini [Department of Environmental Engineering, Technical University of Denmark, Bygningstorvet Bg 115, DK-2800, Kgs Lyngby (Denmark)

2008-11-15

16S rRNA gene targeted oligonucleotide probes for specific detection of genera Thermoanaerobacterium (Tbm1282), Caldicellulosiruptor (Ccs432), and specie Thermoanaerobacterium thermosaccharolyticum (Tbmthsacc184) were designed and used to monitor the spatial distribution of hydrogen producing bacteria in sludge and granules from anaerobic reactors. The designed probes were checked for their specificity and then validated using fluorescence in situ hybridization with target microorganisms and non-target microorganisms. Thermoanaerobacterium spp., T. thermosaccharolyticum and Caldicellulosiruptor spp. were detected with the probes designed with coverage of 75%, 100% and 93%, respectively. Thermophilic (60 C) hydrogen producing reactors, one fed with sucrose and another, fed with palm oil mill effluent comprised of following major groups of hydrogen producers: Thermoanaerobacterium spp. (49% and 36%), T. thermosaccharolyticum (16% and 10%), phylum Firmicutes (low G+C) gram positive bacteria (15% and 27%). Extreme-thermophilic (70 C) hydrogen producing reactors, one fed with xylose and another, fed with lignocellulosic hydrolysate comprised of following major groups of hydrogen producers: Caldicellulosiruptor spp. (40.5% and 20.5%), phylum Firmicutes (low G+C) gram positive bacteria (17% and 20%), Archaea (7% and 8.5%), and Thermoanaerobacterium spp. (0% and 5%). Results obtained, showed good applicability of the probes Tbm1282, Tbmthsacc184 and Ccs432 for specific detection and quantification of thermophilic and extreme-thermophilic hydrogen producers in complex environments. (author)

Laser-pump/X-ray-probe experiments with electrons ejected from a Cu(111) target: space-charge acceleration.

Science.gov (United States)

Schiwietz, G; Kühn, D; Föhlisch, A; Holldack, K; Kachel, T; Pontius, N

2016-09-01

A comprehensive investigation of the emission characteristics for electrons induced by X-rays of a few hundred eV at grazing-incidence angles on an atomically clean Cu(111) sample during laser excitation is presented. Electron energy spectra due to intense infrared laser irradiation are investigated at the BESSY II slicing facility. Furthermore, the influence of the corresponding high degree of target excitation (high peak current of photoemission) on the properties of Auger and photoelectrons liberated by a probe X-ray beam is investigated in time-resolved pump and probe measurements. Strong electron energy shifts have been found and assigned to space-charge acceleration. The variation of the shift with laser power and electron energy is investigated and discussed on the basis of experimental as well as new theoretical results.

Gene probes: principles and protocols

National Research Council Canada - National Science Library

Aquino de Muro, Marilena; Rapley, Ralph

2002-01-01

... of labeled DNA has allowed genes to be mapped to single chromosomes and in many cases to a single chromosome band, promoting significant advance in human genome mapping. Gene Probes: Principles and Protocols presents the principles for gene probe design, labeling, detection, target format, and hybridization conditions together with detailed protocols, accom...

Biocompatibility of photopolymers for additive manufacturing

Directory of Open Access Journals (Sweden)

Leonhardt Stefan

2016-09-01

Full Text Available To establish photopolymers for the production of class II or class III medical products by additive manufacturing it is essential to know which components of photopolymeric systems, consisting of monomers, photoinitiators and additives, are the determining factors on their biocompatible properties. In this study the leachable substances of a cured photopolymeric system were eluted and identified by HPLC-MS detection. In addition the cured photopolymer was testes for cytotoxicity and genotoxicity according to DIN EN ISO 10993 for long time applications. The results showed that uncured residual monomers are the determining factor on the biocompatible properties of the photopolymeric system. Strategies to reduce these residual monomers in the cured photopolymer are presented.

Biocompatibility of hydrogel-based scaffolds for tissue engineering applications.

Science.gov (United States)

Naahidi, Sheva; Jafari, Mousa; Logan, Megan; Wang, Yujie; Yuan, Yongfang; Bae, Hojae; Dixon, Brian; Chen, P

2017-09-01

Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds. Copyright © 2017 Elsevier Inc. All rights reserved.

Hybridization properties of long nucleic acid probes for detection of variable target sequences, and development of a hybridization prediction algorithm

Science.gov (United States)

Öhrmalm, Christina; Jobs, Magnus; Eriksson, Ronnie; Golbob, Sultan; Elfaitouri, Amal; Benachenhou, Farid; Strømme, Maria; Blomberg, Jonas

2010-01-01

One of the main problems in nucleic acid-based techniques for detection of infectious agents, such as influenza viruses, is that of nucleic acid sequence variation. DNA probes, 70-nt long, some including the nucleotide analog deoxyribose-Inosine (dInosine), were analyzed for hybridization tolerance to different amounts and distributions of mismatching bases, e.g. synonymous mutations, in target DNA. Microsphere-linked 70-mer probes were hybridized in 3M TMAC buffer to biotinylated single-stranded (ss) DNA for subsequent analysis in a Luminex® system. When mismatches interrupted contiguous matching stretches of 6 nt or longer, it had a strong impact on hybridization. Contiguous matching stretches are more important than the same number of matching nucleotides separated by mismatches into several regions. dInosine, but not 5-nitroindole, substitutions at mismatching positions stabilized hybridization remarkably well, comparable to N (4-fold) wobbles in the same positions. In contrast to shorter probes, 70-nt probes with judiciously placed dInosine substitutions and/or wobble positions were remarkably mismatch tolerant, with preserved specificity. An algorithm, NucZip, was constructed to model the nucleation and zipping phases of hybridization, integrating both local and distant binding contributions. It predicted hybridization more exactly than previous algorithms, and has the potential to guide the design of variation-tolerant yet specific probes. PMID:20864443

Cellular imaging using biocompatible dendrimer-functionalized graphene oxide-based fluorescent probe anchored with magnetic nanoparticles

International Nuclear Information System (INIS)

Wate, Prateek S; Banerjee, Shashwat S; Mascarenhas, Russel R; Zope, Khushbu R; Khandare, Jayant; Jalota-Badhwar, Archana; Misra, R Devesh K

2012-01-01

We describe a novel multicomponent graphene nanostructured system that is biocompatible, and has strong NIR optical absorbance and superparamagnetic properties. The fabrication of the multicomponent nanostructure system involves the covalent attachment of 3 components; Fe 3 O 4 (Fe) nanoparticles, PAMAM-G4-NH 2 (G4) dendrimer and Cy5 (Cy) on a graphene oxide (GO) surface to synthesize a biologically relevant multifunctional system. The resultant GO-G4-Fe-Cy nanosystem exhibits high dispersion in an aqueous medium, and is magnetically responsive and fluorescent. In vitro experiments provide a clear indication of successful uptake of the GO-G4-Fe-Cy nanosystem by MCF-7 breast cancer cells, and it is seen to behave as a bright and stable fluorescent marker. The study also reveals varied cellular distribution kinetics profile for the GO nanostructured system compared to free Cy. Furthermore, the newly developed GO nanostructured system is observed to be non-toxic to MDA-MB-231 cell growth, in striking contrast to free G4 dendrimer and GO-G4 conjugate. The GO-G4-Fe-Cy nanostructured system characterized by multifunctionality suggests the merits of graphene for cellular bioimaging and the delivery of bioactives. (paper)

Novel Development of Biocompatible Coatings for Bone Implants

Directory of Open Access Journals (Sweden)

Nicholas Yue Hou

2015-10-01

Full Text Available Prolonged life expectancy also results in an increased need for high-performance orthopedic implants. It has been shown that a compromised tissue-implant interface could lead to adverse immune-responses and even the dislodging of the implant. To overcome these obstacles, our research team has been seeking ways to decrease the risk of faulty tissue-implant interfaces by improving the biocompatibility and the osteo-inductivity of conventional orthopedic implants using ultrafine particle coatings. These particles were enriched with various bioactive additives prior to coating, and the coated biomaterial surfaces exhibited significantly increased biocompatibility and osteoinductivity. Physical assessments firstly confirmed the proper incorporation of the bioactive additives after examining their surface chemical composition. Then, in vitro assays demonstrated the biocompatibility and osteo-inductivity of the coated surfaces by studying the morphology of attached cells and their mineralization abilities. In addition, by quantifying the responses, activities and gene expressions, cellular evaluations confirmed the positive effects of these polymer based bioactive coatings. Consequently, the bioactive ultrafine polymer particles demonstrated their ability in improving the biocompatibility and osteo-inductivity of conventional orthopedic implants. As a result, our research team hope to apply this technology to the field of orthopedic implants by making them more effective medical devices through decreasing the risk of implant-induced immune responses and the loosening of the implant.

Biocompatibility of plasma nanostructured biopolymers

Czech Academy of Sciences Publication Activity Database

Kasálková-Slepičková, N.; Slepička, P.; Bačáková, Lucie; Sajdl, P.; Švorčík, V.

2013-01-01

Roč. 307, Jul 15 (2013), s. 642-646 ISSN 0168-583X R&D Projects: GA ČR(CZ) GBP108/12/G108 Institutional support: RVO:67985823 Keywords : biopolymer * plasma treatment * biocompatibility Subject RIV: JJ - Other Materials Impact factor: 1.186, year: 2013

Bilayered near-infrared fluorescent nanoparticles based on low molecular weight PEI for tumor-targeted in vivo imaging

Energy Technology Data Exchange (ETDEWEB)

Liu, Hao; Li, Ke [Xi’an Jiaotong University, Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology (China); Xu, Liang [The University of Kansas, Department of Molecular Biosciences (United States); Wu, Daocheng, E-mail: wudaocheng@mail.xjtu.edu.cn [Xi’an Jiaotong University, Key Laboratory of Biomedical Information Engineering of Education Ministry, School of Life Science and Technology (China)

2014-12-15

To improve the tumor fluorescent imaging results in vivo, bilayered nanoparticles encapsulating a lipophilic near-infrared (NIR) fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotri-carbocyanine iodide (DiR) were prepared using low molecular weight stearic acid-grafted polyethyleneimine and hyaluronic acid (DiR-PgSHA nanoparticles), which were investigated as a novel NIR fluorescent nano-probe for in vivo tumor-targeted optical imaging. These nanoparticles were characterized by transmission electron microscopy (TEM), infrared (IR) spectra, UV-visual absorption, and fluorescent emission spectra. Their cytotoxicity in vitro and hepatotoxicity in vivo were tested by MTT assay and histological study, respectively. In vivo NIR fluorescence imaging of the DiR-PgSHA nanoparticles was performed using a Carestream imaging system. The DiR-PgSHA nanoparticles were sphere shaped with a diameter of approximately 50 nm according to the TEM images. The DiR-PgSHA nanoparticles had a low cytotoxicity in vitro according to the MTT assay and low hepatotoxicity in vivo as determined in histological studies. The fluorescent emission of DiR-PgSHA nanoparticles was stable in pH values of 5–9 in solution, with only slight blue-shifts of the emission maxima at the basic pH range. The DiR-PgSHA nanoparticles exhibited a substantial tumor-targeting ability in the optical imaging with the use of tumor-bearing mice. These results demonstrated that the DiR-PgSHA nanoparticle is an excellent biocompatible nano-probe for in vivo tumor-targeted NIR fluorescence imaging with a potential for clinical applications.

Bilayered near-infrared fluorescent nanoparticles based on low molecular weight PEI for tumor-targeted in vivo imaging

International Nuclear Information System (INIS)

Liu, Hao; Li, Ke; Xu, Liang; Wu, Daocheng

2014-01-01

To improve the tumor fluorescent imaging results in vivo, bilayered nanoparticles encapsulating a lipophilic near-infrared (NIR) fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotri-carbocyanine iodide (DiR) were prepared using low molecular weight stearic acid-grafted polyethyleneimine and hyaluronic acid (DiR-PgSHA nanoparticles), which were investigated as a novel NIR fluorescent nano-probe for in vivo tumor-targeted optical imaging. These nanoparticles were characterized by transmission electron microscopy (TEM), infrared (IR) spectra, UV-visual absorption, and fluorescent emission spectra. Their cytotoxicity in vitro and hepatotoxicity in vivo were tested by MTT assay and histological study, respectively. In vivo NIR fluorescence imaging of the DiR-PgSHA nanoparticles was performed using a Carestream imaging system. The DiR-PgSHA nanoparticles were sphere shaped with a diameter of approximately 50 nm according to the TEM images. The DiR-PgSHA nanoparticles had a low cytotoxicity in vitro according to the MTT assay and low hepatotoxicity in vivo as determined in histological studies. The fluorescent emission of DiR-PgSHA nanoparticles was stable in pH values of 5–9 in solution, with only slight blue-shifts of the emission maxima at the basic pH range. The DiR-PgSHA nanoparticles exhibited a substantial tumor-targeting ability in the optical imaging with the use of tumor-bearing mice. These results demonstrated that the DiR-PgSHA nanoparticle is an excellent biocompatible nano-probe for in vivo tumor-targeted NIR fluorescence imaging with a potential for clinical applications

Synthesis and evaluation of a radioiodinated peptide probe targeting αvβ6 integrin for the detection of pancreatic ductal adenocarcinoma

International Nuclear Information System (INIS)

Ueda, Masashi; Fukushima, Takahiro; Ogawa, Kei; Kimura, Hiroyuki; Ono, Masahiro; Yamaguchi, Takashi; Ikehara, Yuzuru; Saji, Hideo

2014-01-01

Highlights: • We developed a radioiodinated peptide probe targeting αvβ6 integrin ( 123 I-IFMDV2). • 123 I-IFMDV2 had a high affinity and selectivity for αvβ6 integrin. • 123 I-IFMDV2 showed a specific binding to αvβ6 integrin in vivo. • 123 I-IFMDV2 enabled clear visualization of the αvβ6-integrin-positive tumor. - Abstract: Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a major cause of cancer-related death. Since significant upregulation of αvβ6 integrin has been reported in PDAC, this integrin is a promising target for PDAC detection. In this study, we aimed to develop a radioiodinated probe for the imaging of αvβ6 integrin-positive PDAC with single-photon emission computed tomography (SPECT). Methods: Four peptide probes were synthesized and screened by competitive and saturation binding assays using 2 PDAC cell lines (AsPC-1, αvβ6 integrin-positive; MIA PaCa-2, αvβ6 integrin-negative). The probe showing the best affinity was used to study the biodistribution assay, an in vivo blocking study, and SPECT imaging using tumor bearing mice. Autoradiography and immunohistochemical analysis were also performed. Results: Among the 4 probes examined in this study, 125 I-IFMDV2 showed the highest affinity for αvβ6 integrin expressed in AsPC-1 cells and no affinity for MIA PaCa-2 cells. The accumulation of 125 I-IFMDV2 in the AsPC-1 xenograft was 3–5 times greater than that in the MIA PaCa-2 xenograft, consistent with the expression of αvβ6 integrin in each xenograft, and confirmed by immunohistochemistry. Pretreatment with excess amounts of A20FMDV2 significantly blocked the accumulation of 125 I-IFMDV2 in the AsPC-1 xenograft, but not in the MIA PaCa-2 xenograft. Furthermore, 123 I-IFMDV2 enabled clear visualization of the AsPC-1 xenograft. Conclusion: 123 I-IFMDV2 is a potential SPECT probe for the imaging of αvβ6 integrin in PDAC

Shape-dependent surface-enhanced Raman scattering in gold–Raman-probe–silica sandwiched nanoparticles for biocompatible applications

International Nuclear Information System (INIS)

Li Ming; Cushing, Scott K; Lankford, Jessica; Wu, Nianqiang; Zhang Jianming; Ma Dongling; Aguilar, Zoraida P

2012-01-01

To meet the requirement of Raman probes (labels) for biocompatible applications, a synthetic approach has been developed to sandwich the Raman-probe (malachite green isothiocyanate, MGITC) molecules between the gold core and the silica shell in gold–SiO 2 composite nanoparticles. The gold–MGITC–SiO 2 sandwiched structure not only prevents the Raman probe from leaking out but also improves the solubility of the nanoparticles in organic solvents and in aqueous solutions even with high ionic strength. To amplify the Raman signal, three types of core, gold nanospheres, nanorods and nanostars, have been chosen as the substrates of the Raman probe. The effect of the core shape on the surface-enhanced Raman scattering (SERS) has been investigated. The colloidal nanostars showed the highest SERS enhancement factor while the nanospheres possessed the lowest SERS activity under excitation with 532 and 785 nm lasers. Three-dimensional finite-difference time domain (FDTD) simulation showed significant differences in the local electromagnetic field distributions surrounding the nanospheres, nanorods, and nanostars, which were induced by the localized surface plasmon resonance (LSPR). The electromagnetic field was enhanced remarkably around the two ends of the nanorods and around the sharp tips of the nanostars. This local electromagnetic enhancement made the dominant contribution to the SERS enhancement. Both the experiments and the simulation revealed the order nanostars > nanorods > nanospheres in terms of the enhancement factor. Finally, the biological application of the nanostar–MGITC–SiO 2 nanoparticles has been demonstrated in the monitoring of DNA hybridization. In short, the gold–MGITC–SiO 2 sandwiched nanoparticles can be used as a Raman probe that features high sensitivity, good water solubility and stability, low-background fluorescence, and the absence of photobleaching for future biological applications. (paper)

Preparation and properties of superparamagnetic nanoparticles with narrow size distribution and biocompatible

International Nuclear Information System (INIS)

Jiang Wanquan; Yang, H.C.; Yang, S.Y.; Horng, H.E.; Hung, J.C.; Chen, Y.C.; Hong, C.-Y.

2004-01-01

A chemical co-precipitation method capable of controlling the average size and size distribution of magnetic Fe 3 O 4 nano-particles was developed. It was found that the homogeneous variation of the pH value in the solution plays a role in the size distribution of the synthesized Fe 3 O 4 particles. In this work, we added urea to the ferrite solution, followed by heating the solution to decompose the urea before titrating a base solution into the ferrite solution. Thus, the variation in pH value in the solution can become uniform, and the uniformity in the particles size can be greatly enhanced. In addition, the average particle size is adjustable via control of the amount of urea decomposing at one time. To be biocompatible, dextran is selected as the surfactant for the Fe 3 O 4 particles, because of its non-toxicity and high bio-affinity. The desired bio-probes can be coated on the dextran layer through adequate chemical reactions

Linking probe thermodynamics to microarray quantification

International Nuclear Information System (INIS)

Li, Shuzhao; Pozhitkov, Alexander; Brouwer, Marius

2010-01-01

Understanding the difference in probe properties holds the key to absolute quantification of DNA microarrays. So far, Langmuir-like models have failed to link sequence-specific properties to hybridization signals in the presence of a complex hybridization background. Data from washing experiments indicate that the post-hybridization washing has no major effect on the specifically bound targets, which give the final signals. Thus, the amount of specific targets bound to probes is likely determined before washing, by the competition against nonspecific binding. Our competitive hybridization model is a viable alternative to Langmuir-like models. (comment)

Biocompatibility of Niobium Coatings

Directory of Open Access Journals (Sweden)

René Olivares-Navarrete

2011-09-01

Full Text Available Niobium coatings deposited by magnetron sputtering were evaluated as a possible surface modification for stainless steel (SS substrates in biomedical implants. The Nb coatings were deposited on 15 mm diameter stainless steel substrates having an average surface roughness of 2 mm. To evaluate the biocompatibility of the coatings three different in vitro tests, using human alveolar bone derived cells, were performed: cellular adhesion, proliferation and viability. Stainless steel substrates and tissue culture plastic were also studied, in order to give comparative information. No toxic response was observed for any of the surfaces, indicating that the Nb coatings act as a biocompatible, bioinert material. Cell morphology was also studied by immune-fluorescence and the results confirmed the healthy state of the cells on the Nb surface. X-ray diffraction analysis of the coating shows that the film is polycrystalline with a body centered cubic structure. The surface composition and corrosion resistance of both the substrate and the Nb coating were also studied by X-ray photoelectron spectroscopy and potentiodynamic tests. Water contact angle measurements showed that the Nb surface is more hydrophobic than the SS substrate.

Targeted Delivery of Hyaluronan-Immobilized Magnetic Ceramic Nanocrystals.

Science.gov (United States)

Wu, Hsi-Chin; Wang, Tzu-Wei; Hsieh, Shun-Yu; Sun, Jui-Sheng; Kang, Pei-Leun

2016-01-01

Effective cancer therapy relies on delivering the therapeutic agent precisely to the target site to improve the treatment outcome and to minimize side effects. Although surgery, chemotherapy, and radiotherapy are the standard methods commonly used in clinics, hyperthermia has been developed as a new and promising strategy for cancer therapy. In this study, magnetic bioceramic hydroxyapatite (mHAP) nanocrystals have been developed as heat mediator for intracellular hyperthermia. Hyaluronic acid (HA) modified mHAP nanocrystals are synthesized by a wet chemical precipitation process to achieve active targeting. The results demonstrate that the HA targeting moiety conjugated by a poly(ethylene glycol) (PEG) spacer arm is successfully immobilized on the surface of mHAP. The HA-modified mHAP possesses relatively good biocompatibility, an adequate biodegradation rate and superparamagnetic properties. The HA-modified mHAP could be localized and internalized into HA receptor-overexpressed malignant cells (e.g., MDA-MB-231 cell) and used as the heat generating agent for intracellular hyperthermia. The results from this study indicate that biocompatible HA-modified mHAP shows promise as a novel heat mediator and a specific targeting nanoagent for intracellular hyperthermia cancer therapy.

Design, validation and annotation of transcriptome-wide oligonucleotide probes for the oligochaete annelid Eisenia fetida.

Directory of Open Access Journals (Sweden)

Ping Gong

Full Text Available High density oligonucleotide probe arrays have increasingly become an important tool in genomics studies. In organisms with incomplete genome sequence, one strategy for oligo probe design is to reduce the number of unique probes that target every non-redundant transcript through bioinformatic analysis and experimental testing. Here we adopted this strategy in making oligo probes for the earthworm Eisenia fetida, a species for which we have sequenced transcriptome-scale expressed sequence tags (ESTs. Our objectives were to identify unique transcripts as targets, to select an optimal and non-redundant oligo probe for each of these target ESTs, and to annotate the selected target sequences. We developed a streamlined and easy-to-follow approach to the design, validation and annotation of species-specific array probes. Four 244K-formatted oligo arrays were designed using eArray and were hybridized to a pooled E. fetida cRNA sample. We identified 63,541 probes with unsaturated signal intensities consistently above the background level. Target transcripts of these probes were annotated using several sequence alignment algorithms. Significant hits were obtained for 37,439 (59% probed targets. We validated and made publicly available 63.5K oligo probes so the earthworm research community can use them to pursue ecological, toxicological, and other functional genomics questions. Our approach is efficient, cost-effective and robust because it (1 does not require a major genomics core facility; (2 allows new probes to be easily added and old probes modified or eliminated when new sequence information becomes available, (3 is not bioinformatics-intensive upfront but does provide opportunities for more in-depth annotation of biological functions for target genes; and (4 if desired, EST orthologs to the UniGene clusters of a reference genome can be identified and selected in order to improve the target gene specificity of designed probes. This approach is

Cysteine modified polyaniline films improve biocompatibility for two cell lines

Energy Technology Data Exchange (ETDEWEB)

Yslas, Edith I., E-mail: eyslas@exa.unrc.edu.ar [Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Agencia Postal Nro3, X580BYA Río Cuarto (Argentina); Cavallo, Pablo; Acevedo, Diego F.; Barbero, César A. [Departamento de Química, Universidad Nacional de Río Cuarto, Agencia Postal Nro3, X580BYA Río Cuarto (Argentina); Rivarola, Viviana A. [Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, Agencia Postal Nro3, X580BYA Río Cuarto (Argentina)

2015-06-01

This work focuses on one of the most exciting application areas of conjugated conducting polymers, which is cell culture and tissue engineering. To improve the biocompatibility of conducting polymers we present an easy method that involves the modification of the polymer backbone using L-cysteine. In this publication, we show the synthesis of polyaniline (PANI) films supported onto Polyethylene terephthalate (PET) films, and modified using cysteine (PANI-Cys) in order to generate a biocompatible substrate for cell culture. The PANI-Cys films are characterized by Fourier Transform infrared and UV–visible spectroscopy. The changes in the hydrophilicity of the polymer films after and before the modification were tested using contact angle measurements. After modification the contact angle changes from 86° ± 1 to 90° ± 1, suggesting a more hydrophylic surface. The adhesion properties of LM2 and HaCaT cell lines on the surface of PANI-Cys films in comparison with tissue culture plastic (TCP) are studied. The PANI-Cys film shows better biocompatibility than PANI film for both cell lines. The cell morphologies on the TCP and PANI-Cys film were examined by florescence and Atomic Force Microscopy (AFM). Microscopic observations show normal cellular behavior when PANI-Cys is used as a substrate of both cell lines (HaCaT and LM2) as when they are cultured on TCP. The ability of these PANI-Cys films to support cell attachment and growth indicates their potential use as biocompatible surfaces and in tissue engineering. - Highlights: • A new surface PANI-Cys was produced on films of polyethylene terephthalate. • The relationship between surface characteristics and biocompatibility is analyzed. • The PANI-Cys film presents good biocompatibility for two cell lines.

Synthesis and characterization of biocompatible hydroxyapatite ...

Indian Academy of Sciences (India)

Unknown

Indian Institute of Technology, Mumbai 400 076, India. MS received 25 March 2003 ... being given the advantage of a biocompatible coating. The purpose of this work is ..... Financial support from CSIR, New Delhi, is gratefully acknowledged.

Biocompatibility studies of polyacrylonitrile membranes modified with carboxylated polyetherimide

Energy Technology Data Exchange (ETDEWEB)

Senthilkumar, S.; Rajesh, S.; Jayalakshmi, A.; Mohan, D., E-mail: mohantarun@gmail.com

2013-10-15

Poly (ether-imide) (PEI) was carboxylated and used as the hydrophilic modification agent for the preparation of polyacrylonitrile (PAN) membranes. Membranes were prepared with different blend compositions of PAN and CPEI by diffusion induced precipitation. The modified membranes were characterized by thermo gravimetric analysis (TGA), mechanical analysis, scanning electron microscopy (SEM) and contact angle measurement to understand the influence of CPEI on the properties of the membranes. The biocompatibility studies exhibited reduced plasma protein adsorption, platelet adhesion and thrombus formation on the modified membrane surface. The complete blood count (CBC) results of CPEI incorporated membranes showed stable CBC values and significant decrease in the complement activation were also observed. In addition to good cytocompatibility, monocytes cultured on these modified membranes exhibited improved functional profiles in 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Thus it could be concluded that PAN/CPEI membranes with excellent biocompatibility can be useful for hemodialysis. Highlights: • Carboxylated PEI was prepared and utilized as hydrophilic modification agent. • CPEI incorporated into PAN to improved biocompatibility and cyto compatibility • Biocompatibility of membranes was correlated with morphology and hydrophilicity. • Antifouling studies of the PAN/CPEI membranes was studied by BSA as model foulant.

Biomarker selection for determining bone biocompatibility of pure magnesium processed by equal channel angular pressing (ECAP) using immunohistochemistry

Science.gov (United States)

Handayani, Lisa; Sulistyani, Lilies Dwi; Supriadi, Sugeng; Priosoeryanto, Bambang Pontjo; Latief, Benny Syariefsyah

2018-02-01

Since grain refinement is proved to be favorable to improve mechanical properties and corrosion resistance, a new conceptual metal forming process, equal channel angular pressing (ECAP), has been carried out on magnesium, a very promising biodegradable material in the field of oral and maxillofacial surgery. The popularity of immunohisto-chemistry (IHC) has been rising following the discovery of biomarker. In the meantime, more antibodies being produced for research have been continuously rising and becoming more varied. This review provides a conceptual framework to understand the roles of IHC on determination of bone biocompatibility to ECAP magnesium by selecting biomarker and point needed to either select or make an antibody to the target. From the review, it has been concluded that the most suitable biomarkers for biocompatibility test of bone implanted with ECAP magnesium are collagen-1, osteocalcin, smooth muscle actin, and CD68.

A Pyridazine-Based Fluorescent Probe Targeting Aβ Plaques in Alzheimer’s Disease

Directory of Open Access Journals (Sweden)

Yong Dae Park

2018-01-01

Full Text Available Accumulation of β-amyloid (Aβ plaques comprising Aβ40 and Aβ42 in the brain is the most significant factor in the pathogenesis of Alzheimer’s disease (AD. Thus, the detection of Aβ plaques has increasingly attracted interest in the context of AD diagnosis. In the present study, a fluorescent pyridazine-based dye that can detect and image Aβ plaques was designed and synthesized, and its optical properties in the presence of Aβ aggregates were evaluated. An approximately 34-fold increase in emission intensity was exhibited by the fluorescent probe after binding with Aβ aggregates, for which it showed high affinity (KD = 0.35 µM. Moreover, the reasonable hydrophobic properties of the probe (log P = 2.94 allow it to penetrate the blood brain barrier (BBB. In addition, the pyridazine-based probe was used in the histological costaining of transgenic mouse (APP/PS1 brain sections to validate the selective binding of the probe to Aβ plaques. The results suggest that the pyridazine-based compound has the potential to serve as a fluorescent probe for the diagnosis of AD.

Different Storage Conditions Influence Biocompatibility and Physicochemical Properties of Iron Oxide Nanoparticles

Directory of Open Access Journals (Sweden)

Jan Zaloga

2015-04-01

Full Text Available Superparamagnetic iron oxide nanoparticles (SPIONs have attracted increasing attention in many biomedical fields. In magnetic drug targeting SPIONs are injected into a tumour supplying artery and accumulated inside the tumour with a magnet. The effectiveness of this therapy is thus dependent on magnetic properties, stability and biocompatibility of the particles. A good knowledge of the effect of storage conditions on those parameters is of utmost importance for the translation of the therapy concept into the clinic and for reproducibility in preclinical studies. Here, core shell SPIONs with a hybrid coating consisting of lauric acid and albumin were stored at different temperatures from 4 to 45 °C over twelve weeks and periodically tested for their physicochemical properties over time. Surprisingly, even at the highest storage temperature we did not observe denaturation of the protein or colloidal instability. However, the saturation magnetisation decreased by maximally 28.8% with clear correlation to time and storage temperature. Furthermore, the biocompatibility was clearly affected, as cellular uptake of the SPIONs into human T-lymphoma cells was crucially dependent on the storage conditions. Taken together, the results show that the particle properties undergo significant changes over time depending on the way they are stored.

Labeling mesenchymal cells with DMSA-coated gold and iron oxide nanoparticles: assessment of biocompatibility and potential applications.

Science.gov (United States)

Silva, Luisa H A; da Silva, Jaqueline R; Ferreira, Guilherme A; Silva, Renata C; Lima, Emilia C D; Azevedo, Ricardo B; Oliveira, Daniela M

2016-07-18

Nanoparticles' unique features have been highly explored in cellular therapies. However, nanoparticles can be cytotoxic. The cytotoxicity can be overcome by coating the nanoparticles with an appropriated surface modification. Nanoparticle coating influences biocompatibility between nanoparticles and cells and may affect some cell properties. Here, we evaluated the biocompatibility of gold and maghemite nanoparticles functionalized with 2,3-dimercaptosuccinic acid (DMSA), Au-DMSA and γ-Fe2O3-DMSA respectively, with human mesenchymal stem cells. Also, we tested these nanoparticles as tracers for mesenchymal stem cells in vivo tracking by computed tomography and as agents for mesenchymal stem cells magnetic targeting. Significant cell death was not observed in MTT, Trypan Blue and light microscopy analyses. However, ultra-structural alterations as swollen and degenerated mitochondria, high amounts of myelin figures and structures similar to apoptotic bodies were detected in some mesenchymal stem cells. Au-DMSA and γ-Fe2O3-DMSA labeling did not affect mesenchymal stem cells adipogenesis and osteogenesis differentiation, proliferation rates or lymphocyte suppression capability. The uptake measurements indicated that both inorganic nanoparticles were well uptaken by mesenchymal stem cells. However, Au-DMSA could not be detected in microtomograph after being incorporated by mesenchymal stem cells. γ-Fe2O3-DMSA labeled cells were magnetically responsive in vitro and after infused in vivo in an experimental model of lung silicosis. In terms of biocompatibility, the use of γ-Fe2O3-DMSA and Au-DMSA as tracers for mesenchymal stem cells was assured. However, Au-DMSA shown to be not suitable for visualization and tracking of these cells in vivo by standard computed microtomography. Otherwise, γ-Fe2O3-DMSA shows to be a promising agent for mesenchymal stem cells magnetic targeting.

Corrosion resistance and biocompatibility of zirconium oxynitride thin film growth by RF sputtering

Energy Technology Data Exchange (ETDEWEB)

Cubillos, G. I.; Olaya, J. J.; Clavijo, D.; Alfonso, J. E. [Universidad Nacional de Colombia, Carrera 45 No. 26-85, AA 14490 Bogota D. C. (Colombia); Bethencourt, M., E-mail: jealfonsoo@unal.edu.co [Universidad de Cadiz, Centro Andaluz de Ciencia y Tecnologia Marinas, Departamento de Ciencia de los Materiales e Ingenieria Metalurgica y Quimica Inorganica, Av. Republica de Saharaui, Puerto Real, E-11510 Cadiz (Spain)

2012-07-01

Thin films of zirconium oxynitride were grown on common glass, silicon (100) and stainless steel 316 L substrates using the reactive RF magnetron sputtering technique. The films were analyzed through structural, morphological and biocompatibility studies. The structural analysis was carried out using X-ray diffraction (XRD), and the morphological analysis was carried out using scanning electron microscopy (Sem) and atomic force microscopy (AFM). These studies were done as a function of growth parameters, such as power applied to the target, substrate temperature, and flow ratios. The corrosion resistance studies were made on samples of stainless steel 316 L coated and uncoated with Zr{sub x}N{sub y}O films, through of polarization curves. The studies of biocompatibility were carried out on zirconium oxynitride films deposited on stainless steel 316 L through proliferation and cellular adhesion. The XRD analysis shows that films deposited at 623 K, with a flow ratio {Phi}N{sub 2}/{Phi}O{sub 2} of 1.25 and a total deposit time of 30 minutes grew preferentially oriented along the (111) plane of the zirconium oxynitride monoclinic phase. The Sem analyses showed that the films grew homogeneously, and the AFM studies indicated that the average rugosity of the film was 5.9 nm and the average particle size was 150 nm. The analysis of the corrosion resistant, shows that the stainless steel coated with the film was increased a factor 10. Finally; through the analysis of the biocompatibility we established that the films have a better surface than the substrate (stainless steel 316 L) in terms of the adhesion and proliferation of bone cells. (Author)

Electroactive biocompatible materials for nerve cell stimulation

International Nuclear Information System (INIS)

Yang, Mei; Liang, Youlong; Gui, Qingyuan; Liu, Yong; Chen, Jun

2015-01-01

In the past decades, great efforts have been developed for neurobiologists and neurologists to restore nervous system functions. Recently much attention has been paid to electrical stimulation (ES) of the nervous system as a potential way to repair it. Various conductive biocompatible materials with good electrical conductivity, biocompatibility, and long-term ES or electrical stability have been developed as the substrates for ES. In this review, we summarized different types of materials developed in the purpose for ES of nervous system, including conducting polymers, carbon nanomaterials and composites from conducting polymer/carbon nanomaterials. The present review will give our perspective on the future research directions for further investigation on development of ES particularly on the nerve system. (topical review)

A Ratiometric Acoustogenic Probe for in Vivo Imaging of Endogenous Nitric Oxide.

Science.gov (United States)

Reinhardt, Christopher J; Zhou, Effie Y; Jorgensen, Michael D; Partipilo, Gina; Chan, Jefferson

2018-01-24

Photoacoustic (PA) imaging is an emerging imaging modality that utilizes optical excitation and acoustic detection to enable high resolution at centimeter depths. The development of activatable PA probes can expand the utility of this technology to allow for detection of specific stimuli within live-animal models. Herein, we report the design, development, and evaluation of a series of Acoustogenic Probe(s) for Nitric Oxide (APNO) for the ratiometric, analyte-specific detection of nitric oxide (NO) in vivo. The best probe in the series, APNO-5, rapidly responds to NO to form an N-nitroso product with a concomitant 91 nm hypsochromic shift. This property enables ratiometric PA imaging upon selective irradiation of APNO-5 and the corresponding product, tAPNO-5. Moreover, APNO-5 displays the requisite photophysical characteristics for in vivo PA imaging (e.g., high absorptivity, low quantum yield) as well as high biocompatibility, stability, and selectivity for NO over a variety of biologically relevant analytes. APNO-5 was successfully applied to the detection of endogenous NO in a murine lipopolysaccharide-induced inflammation model. Our studies show a 1.9-fold increase in PA signal at 680 nm and a 1.3-fold ratiometric turn-on relative to a saline control.

Protease-activated quantum dot probes

International Nuclear Information System (INIS)

Chang, Emmanuel; Miller, Jordan S.; Sun, Jiantang; Yu, William W.; Colvin, Vicki L.; Drezek, Rebekah; West, Jennifer L.

2005-01-01

We have developed a novel nanoparticulate luminescent probe with inherent signal amplification upon interaction with a targeted proteolytic enzyme. This construct may be useful for imaging in cancer detection and diagnosis. In this system, quantum dots (QDs) are bound to gold nanoparticles (AuNPs) via a proteolytically degradable peptide sequence to non-radiatively suppress luminescence. A 71% reduction in luminescence was achieved with conjugation of AuNPs to QDs. Release of AuNPs by peptide cleavage restores radiative QD photoluminescence. Initial studies observed a 52% rise in luminescence over 47 h of exposure to 0.2 mg/mL collagenase. These probes can be customized for targeted degradation simply by changing the sequence of the peptide linker

Biocompatible 3D printed magnetic micro needles

KAUST Repository

Kavaldzhiev, Mincho

2017-01-30

Biocompatible functional materials play a significant role in drug delivery, tissue engineering and single cell analysis. We utilized 3D printing to produce high aspect ratio polymer resist microneedles on a silicon substrate and functionalized them by iron coating. Two-photon polymerization lithography has been used for printing cylindrical, pyramidal, and conical needles from a drop cast IP-DIP resist. Experiments with cells were conducted with cylindrical microneedles with 630 ± 15 nm in diameter with an aspect ratio of 1:10 and pitch of 12 μm. The needles have been arranged in square shaped arrays with various dimensions. The iron coating of the needles was 120 ± 15 nm thick and has isotropic magnetic behavior. The chemical composition and oxidation state were determined using energy electron loss spectroscopy, revealing a mixture of iron and Fe3O4 clusters. A biocompatibility assessment was performed through fluorescence microscopy using calcein/EthD-1 live/dead assay. The results show a very high biocompatibility of the iron coated needle arrays. This study provides a strategy to obtain electromagnetically functional microneedles that benefit from the flexibility in terms of geometry and shape of 3D printing. Potential applications are in areas like tissue engineering, single cell analysis or drug delivery.

Biocompatible 3D printed magnetic micro needles

KAUST Repository

Kavaldzhiev, Mincho; Perez, Jose E.; Ivanov, Yurii; Bertoncini, Andrea; Liberale, Carlo; Kosel, Jü rgen

2017-01-01

Biocompatible functional materials play a significant role in drug delivery, tissue engineering and single cell analysis. We utilized 3D printing to produce high aspect ratio polymer resist microneedles on a silicon substrate and functionalized them by iron coating. Two-photon polymerization lithography has been used for printing cylindrical, pyramidal, and conical needles from a drop cast IP-DIP resist. Experiments with cells were conducted with cylindrical microneedles with 630 ± 15 nm in diameter with an aspect ratio of 1:10 and pitch of 12 μm. The needles have been arranged in square shaped arrays with various dimensions. The iron coating of the needles was 120 ± 15 nm thick and has isotropic magnetic behavior. The chemical composition and oxidation state were determined using energy electron loss spectroscopy, revealing a mixture of iron and Fe3O4 clusters. A biocompatibility assessment was performed through fluorescence microscopy using calcein/EthD-1 live/dead assay. The results show a very high biocompatibility of the iron coated needle arrays. This study provides a strategy to obtain electromagnetically functional microneedles that benefit from the flexibility in terms of geometry and shape of 3D printing. Potential applications are in areas like tissue engineering, single cell analysis or drug delivery.

Advances in Probes and Methods for Clinical EPR Oximetry

Science.gov (United States)

Hou, Huagang; Khan, Nadeem; Jarvis, Lesley A.; Chen, Eunice Y.; Williams, Benjamin B.; Kuppusamy, Periannan

2015-01-01

EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR oximetry for small animal models of disease, we are developing suitable probes and instrumentation required for use in human subjects. Our laboratory has established the feasibility of clinical EPR oximetry in cancer patients using India ink, the only material presently approved for clinical use. We now are developing the next generation of probes, which are both superior in terms of oxygen sensitivity and biocompatibility including an excellent safety profile for use in humans. Further advances include the development of implantable oxygen sensors linked to an external coupling loop for measurements of deep-tissue oxygenations at any depth, overcoming the current limitation of 10 mm. This paper presents an overview of recent developments in our ability to make meaningful measurements of oxygen partial pressures in human subjects under clinical settings. PMID:24729217

Bioglass: A novel biocompatible innovation.

Science.gov (United States)

Krishnan, Vidya; Lakshmi, T

2013-04-01

Advancement of materials technology has been immense, especially in the past 30 years. Ceramics has not been new to dentistry. Porcelain crowns, silica fillers in composite resins, and glass ionomer cements have already been proved to be successful. Materials used in the replacement of tissues have come a long way from being inert, to compatible, and now regenerative. When hydroxyapatite was believed to be the best biocompatible replacement material, Larry Hench developed a material using silica (glass) as the host material, incorporated with calcium and phosphorous to fuse broken bones. This material mimics bone material and stimulates the regrowth of new bone material. Thus, due to its biocompatibility and osteogenic capacity it came to be known as "bioactive glass-bioglass." It is now encompassed, along with synthetic hydroxyapatite, in the field of biomaterials science known as "bioactive ceramics." The aim of this article is to give a bird's-eye view, of the various uses in dentistry, of this novel, miracle material which can bond, induce osteogenesis, and also regenerate bone.

Bioglass: A novel biocompatible innovation

Directory of Open Access Journals (Sweden)

Vidya Krishnan

2013-01-01

Full Text Available Advancement of materials technology has been immense, especially in the past 30 years. Ceramics has not been new to dentistry. Porcelain crowns, silica fillers in composite resins, and glass ionomer cements have already been proved to be successful. Materials used in the replacement of tissues have come a long way from being inert, to compatible, and now regenerative. When hydroxyapatite was believed to be the best biocompatible replacement material, Larry Hench developed a material using silica (glass as the host material, incorporated with calcium and phosphorous to fuse broken bones. This material mimics bone material and stimulates the regrowth of new bone material. Thus, due to its biocompatibility and osteogenic capacity it came to be known as "bioactive glass-bioglass." It is now encompassed, along with synthetic hydroxyapatite, in the field of biomaterials science known as "bioactive ceramics." The aim of this article is to give a bird′s-eye view, of the various uses in dentistry, of this novel, miracle material which can bond, induce osteogenesis, and also regenerate bone.

Biocompatibility of Bletilla striata Microspheres as a Novel Embolic Agent

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ShiHua Luo

2015-01-01

Full Text Available We have prepared Chinese traditional herb Bletilla striata into microspheres as a novel embolic agent for decades. The aim of this study was to evaluate the biocompatibility of Bletilla striata microspheres (BSMs. After a thermal test of BSMs in vitro, the cell biocompatibility of BSMs was investigated in mouse fibroblasts and human umbilical vein endothelial cells using the methyl tetrazolium (MTT assay. In addition, blood biocompatibility was evaluated. In vivo intramuscular implantation and renal artery embolization in rabbits with BSMs were used to examine the inflammatory response. The experimental rabbits did not develop any fever symptoms after injection of BSMs, and BSMs exhibited no cytotoxicity in cultured mouse fibroblasts and human umbilical vein endothelial cells. Additionally, BSMs exhibited high compatibility with red blood cells and no hemolysis activity. Intramuscular implantation with BSMs resulted in a gradually lessened mild inflammatory reaction that disappeared after eight weeks. The occlusion of small renal vessels was associated with a mild perivascular inflammatory reaction without significant renal and liver function damage. In conclusion, we believe that BSMs exhibit high biocompatibility and are a promising embolic agent.

A fluorescent nanosensor based on graphene quantum dots-aptamer probe and graphene oxide platform for detection of lead (II) ion.

Science.gov (United States)

Qian, Zhao Sheng; Shan, Xiao Yue; Chai, Lu Jing; Chen, Jian Rong; Feng, Hui

2015-06-15

The sensitive detection of heavy metal ions in the organism and aquatic ecosystem using nanosensors based on environment friendly and biocompatible materials still remains a challenge. A fluorescent turn-on nanosensor for lead (II) detection based on biocompatible graphene quantum dots and graphene oxide by employment of Pb(2+)-induced G-quadruplex formation was reported. Graphene quantum dots with high quantum yield, good biocompatibility were prepared and served as the fluorophore of Pb(2+) probe. Fluorescence turn-off of graphene quantum dots is easily achieved through efficient photoinduced electron transfer between graphene quantum dots and graphene oxide, and subsequent fluorescence turn-on process is due to the formation of G-quadraplex aptamer-Pb(2+) complex triggered by the addition of Pb(2+). This nanosensor can distinguish Pb(2+) ion from other ions with high sensitivity and good reproducibility. The detection method based on this nanosensor possesses a fast response time of one minute, a broad linear span of up to 400.0 nM and ultralow detection limit of 0.6 nM. Copyright © 2015 Elsevier B.V. All rights reserved.

In situ, accurate, surface-enhanced Raman scattering detection of cancer cell nucleus with synchronous location by an alkyne-labeled biomolecular probe.

Science.gov (United States)

Zhang, Jing; Liang, Lijia; Guan, Xin; Deng, Rong; Qu, Huixin; Huang, Dianshuai; Xu, Shuping; Liang, Chongyang; Xu, Weiqing

2018-01-01

A surface-enhanced Raman scattering (SERS) method for in situ detection and analysis of the intranuclear biomolecular information of a cell has been developed based on a small, biocompatible, nuclear-targeting alkyne-tagged deoxyribonucleic acid (DNA) probe (5-ethynyl-2'-deoxyuridine, EDU) that can specially accumulate in the cell nucleus during DNA replications to precisely locate the nuclear region without disturbance in cell biological activities and functions. Since the specific alkyne group shows a Raman peak in the Raman-silent region of cells, it is an interior label to visualize the nuclear location synchronously in real time when measuring the SERS spectra of a cell. Because no fluorescent-labeled dyes were used for locating cell nuclei, this method is simple, nondestructive, non- photobleaching, and valuable for the in situ exploration of vital physiological processes with DNA participation in cell organelles. Graphical abstract A universal strategy was developed to accurately locate the nuclear region and obtain precise molecular information of cell nuclei by SERS.

In Vitro Models in BiocompatibilityAssessment for Biomedical-Grade Chitosan Derivatives in Wound Management

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Lim Chin Keong

2009-03-01

Full Text Available One of the ultimate goals of wound healing research is to find effective healing techniques that utilize the regeneration of similar tissues. This involves the modification of various wound dressing biomaterials for proper wound management. The biopolymer chitosan (b-1,4-D-glucosamine has natural biocompatibility and biodegradability that render it suitable for wound management. By definition, a biocompatible biomaterial does not have toxic or injurious effects on biological systems. Chemical and physical modifications of chitosan influence its biocompatibility and biodegradability to an uncertain degree. Hence, the modified biomedical-grade of chitosan derivatives should be pre-examined in vitro in order to produce high-quality, biocompatible dressings. In vitro toxicity examinations are more favorable than those performed in vivo, as the results are more reproducible and predictive. In this paper, basic in vitro tools were used to evaluate cellular and molecular responses with regard to the biocompatibility of biomedical-grade chitosan. Three paramount experimental parameters of biocompatibility in vitro namely cytocompatibility, genotoxicity and skin pro-inflammatory cytokine expression, were generally reviewed for biomedical-grade chitosan as wound dressing.

Targeting low-density lipoprotein receptors with protein-only nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Xu, Zhikun [Universitat Autònoma de Barcelona, Institut de Biotecnologia i de Biomedicina (Spain); Céspedes, María Virtudes [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Unzueta, Ugutz [Universitat Autònoma de Barcelona, Institut de Biotecnologia i de Biomedicina (Spain); Álamo, Patricia [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Pesarrodona, Mireia [Universitat Autònoma de Barcelona, Institut de Biotecnologia i de Biomedicina (Spain); Mangues, Ramón [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Vázquez, Esther; Villaverde, Antonio, E-mail: antoni.villaverde@uab.cat; Ferrer-Miralles, Neus, E-mail: neus.ferrer@uab.cat [Universitat Autònoma de Barcelona, Institut de Biotecnologia i de Biomedicina (Spain)

2015-03-15

Low-density lipoprotein receptors (LDLR) are appealing cell surface targets in drug delivery, as they are expressed in the blood–brain barrier (BBB) endothelium and are able to mediate transcytosis of functionalized drugs for molecular therapies of the central nervous system (CNS). On the other hand, brain-targeted drug delivery is currently limited, among others, by the poor availability of biocompatible vehicles, as most of the nanoparticles under development as drug carriers pose severe toxicity issues. In this context, protein nanoparticles offer functional versatility, easy and cost-effective bioproduction, and full biocompatibility. In this study, we have designed and characterized several chimerical proteins containing different LDLR ligands, regarding their ability to bind and internalize target cells and to self-organize as viral mimetic nanoparticles of about 18 nm in diameter. While the self-assembling of LDLR-binding proteins as nanoparticles positively influences cell penetration in vitro, the nanoparticulate architecture might be not favoring BBB crossing in vivo. These findings are discussed in the context of the use of nanostructured materials as vehicles for the systemic treatment of CNS diseases.

Targeting low-density lipoprotein receptors with protein-only nanoparticles

International Nuclear Information System (INIS)

Xu, Zhikun; Céspedes, María Virtudes; Unzueta, Ugutz; Álamo, Patricia; Pesarrodona, Mireia; Mangues, Ramón; Vázquez, Esther; Villaverde, Antonio; Ferrer-Miralles, Neus

2015-01-01

Low-density lipoprotein receptors (LDLR) are appealing cell surface targets in drug delivery, as they are expressed in the blood–brain barrier (BBB) endothelium and are able to mediate transcytosis of functionalized drugs for molecular therapies of the central nervous system (CNS). On the other hand, brain-targeted drug delivery is currently limited, among others, by the poor availability of biocompatible vehicles, as most of the nanoparticles under development as drug carriers pose severe toxicity issues. In this context, protein nanoparticles offer functional versatility, easy and cost-effective bioproduction, and full biocompatibility. In this study, we have designed and characterized several chimerical proteins containing different LDLR ligands, regarding their ability to bind and internalize target cells and to self-organize as viral mimetic nanoparticles of about 18 nm in diameter. While the self-assembling of LDLR-binding proteins as nanoparticles positively influences cell penetration in vitro, the nanoparticulate architecture might be not favoring BBB crossing in vivo. These findings are discussed in the context of the use of nanostructured materials as vehicles for the systemic treatment of CNS diseases

[Development of a Fluorescence Probe for Live Cell Imaging].

Science.gov (United States)

Shibata, Aya

2017-01-01

 Probes that detect specific biological materials are indispensable tools for deepening our understanding of various cellular phenomena. In live cell imaging, the probe must emit fluorescence only when a specific substance is detected. In this paper, we introduce a new probe we developed for live cell imaging. Glutathione S-transferase (GST) activity is higher in tumor cells than in normal cells and is involved in the development of resistance to various anticancer drugs. We previously reported the development of a general strategy for the synthesis of probes for detection of GST enzymes, including fluorogenic, bioluminogenic, and 19 F-NMR probes. Arylsulfonyl groups were used as caging groups during probe design. The fluorogenic probes were successfully used to quantitate very low levels of GST activity in cell extracts and were also successfully applied to the imaging of microsomal MGST1 activity in living cells. The bioluminogenic and 19 F-NMR probes were able to detect GST activity in Escherichia coli cells. Oligonucleotide-templated reactions are powerful tools for nucleic acid sensing. This strategy exploits the target strand as a template for two functionalized probes and provides a simple molecular mechanism for multiple turnover reactions. We developed a nucleophilic aromatic substitution reaction-triggered fluorescent probe. The probe completed its reaction within 30 s of initiation and amplified the fluorescence signal from 0.5 pM target oligonucleotide by 1500 fold under isothermal conditions. Additionally, we applied the oligonucleotide-templated reaction for molecular releasing and peptide detection.

Expanding probe repertoire and improving reproducibility in human genomic hybridization

Science.gov (United States)

Dorman, Stephanie N.; Shirley, Ben C.; Knoll, Joan H. M.; Rogan, Peter K.

2013-01-01

Diagnostic DNA hybridization relies on probes composed of single copy (sc) genomic sequences. Sc sequences in probe design ensure high specificity and avoid cross-hybridization to other regions of the genome, which could lead to ambiguous results that are difficult to interpret. We examine how the distribution and composition of repetitive sequences in the genome affects sc probe performance. A divide and conquer algorithm was implemented to design sc probes. With this approach, sc probes can include divergent repetitive elements, which hybridize to unique genomic targets under higher stringency experimental conditions. Genome-wide custom probe sets were created for fluorescent in situ hybridization (FISH) and microarray genomic hybridization. The scFISH probes were developed for detection of copy number changes within small tumour suppressor genes and oncogenes. The microarrays demonstrated increased reproducibility by eliminating cross-hybridization to repetitive sequences adjacent to probe targets. The genome-wide microarrays exhibited lower median coefficients of variation (17.8%) for two HapMap family trios. The coefficients of variations of commercial probes within 300 nt of a repetitive element were 48.3% higher than the nearest custom probe. Furthermore, the custom microarray called a chromosome 15q11.2q13 deletion more consistently. This method for sc probe design increases probe coverage for FISH and lowers variability in genomic microarrays. PMID:23376933

Mass amplifying probe for sensitive fluorescence anisotropy detection of small molecules in complex biological samples.

Science.gov (United States)

Cui, Liang; Zou, Yuan; Lin, Ninghang; Zhu, Zhi; Jenkins, Gareth; Yang, Chaoyong James

2012-07-03

Fluorescence anisotropy (FA) is a reliable and excellent choice for fluorescence sensing. One of the key factors influencing the FA value for any molecule is the molar mass of the molecule being measured. As a result, the FA method with functional nucleic acid aptamers has been limited to macromolecules such as proteins and is generally not applicable for the analysis of small molecules because their molecular masses are relatively too small to produce observable FA value changes. We report here a molecular mass amplifying strategy to construct anisotropy aptamer probes for small molecules. The probe is designed in such a way that only when a target molecule binds to the probe does it activate its binding ability to an anisotropy amplifier (a high molecular mass molecule such as protein), thus significantly increasing the molecular mass and FA value of the probe/target complex. Specifically, a mass amplifying probe (MAP) consists of a targeting aptamer domain against a target molecule and molecular mass amplifying aptamer domain for the amplifier protein. The probe is initially rendered inactive by a small blocking strand partially complementary to both target aptamer and amplifier protein aptamer so that the mass amplifying aptamer domain would not bind to the amplifier protein unless the probe has been activated by the target. In this way, we prepared two probes that constitute a target (ATP and cocaine respectively) aptamer, a thrombin (as the mass amplifier) aptamer, and a fluorophore. Both probes worked well against their corresponding small molecule targets, and the detection limits for ATP and cocaine were 0.5 μM and 0.8 μM, respectively. More importantly, because FA is less affected by environmental interferences, ATP in cell media and cocaine in urine were directly detected without any tedious sample pretreatment. Our results established that our molecular mass amplifying strategy can be used to design aptamer probes for rapid, sensitive, and selective

Enhanced fluorescence imaging of live cells by effective cytosolic delivery of probes.

Directory of Open Access Journals (Sweden)

Marzia Massignani

Full Text Available BACKGROUND: Microscopic techniques enable real-space imaging of complex biological events and processes. They have become an essential tool to confirm and complement hypotheses made by biomedical scientists and also allow the re-examination of existing models, hence influencing future investigations. Particularly imaging live cells is crucial for an improved understanding of dynamic biological processes, however hitherto live cell imaging has been limited by the necessity to introduce probes within a cell without altering its physiological and structural integrity. We demonstrate herein that this hurdle can be overcome by effective cytosolic delivery. PRINCIPAL FINDINGS: We show the delivery within several types of mammalian cells using nanometre-sized biomimetic polymer vesicles (a.k.a. polymersomes that offer both highly efficient cellular uptake and endolysomal escape capability without any effect on the cellular metabolic activity. Such biocompatible polymersomes can encapsulate various types of probes including cell membrane probes and nucleic acid probes as well as labelled nucleic acids, antibodies and quantum dots. SIGNIFICANCE: We show the delivery of sufficient quantities of probes to the cytosol, allowing sustained functional imaging of live cells over time periods of days to weeks. Finally the combination of such effective staining with three-dimensional imaging by confocal laser scanning microscopy allows cell imaging in complex three-dimensional environments under both mono-culture and co-culture conditions. Thus cell migration and proliferation can be studied in models that are much closer to the in vivo situation.

Design, synthesis and validation of integrin α2β1-targeted probe for microPET imaging of prostate cancer

International Nuclear Information System (INIS)

Huang, Chiun-Wei; Li, Zibo; Cai, Hancheng; Chen, Kai; Shahinian, Tony; Conti, Peter S.

2011-01-01

The ability of PET to aid in the diagnosis and management of recurrent and/or disseminated metastatic prostate cancer may be enhanced by the development of novel prognostic imaging probes. Accumulating experimental evidence indicates that overexpression of integrin α 2 β 1 may correlate with progression in human prostate cancer. In this study, 64 Cu-labeled integrin α 2 β 1 -targeted PET probes were designed and evaluated for the imaging of prostate cancer. DGEA peptides conjugated with a bifunctional chelator (BFC) were developed to image integrin α 2 β 1 expression with PET in a subcutaneous PC-3 xenograft model. The microPET images were reconstructed by a two-dimensional ordered subsets expectation maximum algorithm. The average radioactivity accumulation within a tumor or an organ was quantified from the multiple region of interest volumes. The PET tracer demonstrated prominent tumor uptake in the PC-3 xenograft (integrin α 2 β 1 -positive). The receptor specificity was confirmed in a blocking experiment. Moreover, the low tracer uptake in a CWR-22 tumor model (negative control) further confirmed the receptor specificity. The sarcophagine-conjugated DGEA peptide allows noninvasive imaging of tumor-associated α 2 β 1 expression, which may be a useful PET probe for evaluating the metastatic potential of prostate cancer. (orig.)

Biocompatible Peritoneal Dialysis Fluids: Clinical Outcomes

Directory of Open Access Journals (Sweden)

Yeoungjee Cho

2012-01-01

Full Text Available Peritoneal dialysis (PD is a preferred home dialysis modality and has a number of added advantages including improved initial patient survival and cost effectiveness over haemodialysis. Despite these benefits, uptake of PD remains relatively low, especially in developed countries. Wider implementation of PD is compromised by higher technique failure from infections (e.g., PD peritonitis and ultrafiltration failure. These are inevitable consequences of peritoneal injury, which is thought to result primarily from continuous exposure to PD fluids that are characterised by their “unphysiologic” composition. In order to overcome these barriers, a number of more biocompatible PD fluids, with neutral pH, low glucose degradation product content, and bicarbonate buffer have been manufactured over the past two decades. Several preclinical studies have demonstrated their benefit in terms of improvement in host cell defence, peritoneal membrane integrity, and cytokine profile. This paper aims to review randomised controlled trials assessing the use of biocompatible PD fluids and their effect on clinical outcomes.

Functionalization of {gamma}-alumina cores by polyvinylpirrolidone: properties of the resulting biocompatible nanoparticles in aqueous suspension

Energy Technology Data Exchange (ETDEWEB)

Fernandez, L. [Universidad Nacional del Comahue, Dpto de Quimica, Facultad de Ingenieria (Argentina); Arranz, G.; Palacio, L. [Universidad de Valladolid, Dpto. Fisica Aplicada, Facultad de Ciencias (Spain); Soria, C.; Sanchez, M.; Perez, G. [Universidad Nacional del Comahue, Dpto de Quimica, Facultad de Ingenieria (Argentina); Lozano, A. E. [UA-CSIC-UVA, Surface and Porous Materials (SMAP) (Spain); Hernandez, A.; Pradanos, P., E-mail: pradanos@termo.uva.e [Universidad de Valladolid, Dpto. Fisica Aplicada, Facultad de Ciencias (Spain)

2009-02-15

A biocompatible polymer has been used to functionalize 45-50 nm diameter {gamma}-alumina nanoparticles. Because the target was to use these systems in real applications, polyvinylpirrolidone (PVP) was chosen due to the characteristics of non-toxicity, biocompatibility, and feasibility of this polymer to form complexes with many cations and chemical species. This approach allows the use of these materials in medicine and food, textile, or pharmaceutical industry. The functionalization process required a previous attachment of an active group on the surface of the nanoparticles. Subsequently, a polymer chain was generated in situ, using vinyltrimethoxysilane (VTMS) and 1-vinyl-2-pyrrolidone (VP) as reactives. The morphology and topology of the nanocompound has been characterized in aqueous suspensions, attending to possible applications in this medium. The results obtained from the different techniques show that the polymer chain was successfully grafted to the nanoparticle surface, and allow an estimation of the size of the modified particle. Their electrical and conformational behavior have also been studied in different aqueous chemical environments.

Functionalization of γ-alumina cores by polyvinylpirrolidone: properties of the resulting biocompatible nanoparticles in aqueous suspension

International Nuclear Information System (INIS)

Fernandez, L.; Arranz, G.; Palacio, L.; Soria, C.; Sanchez, M.; Perez, G.; Lozano, A. E.; Hernandez, A.; Pradanos, P.

2009-01-01

A biocompatible polymer has been used to functionalize 45-50 nm diameter γ-alumina nanoparticles. Because the target was to use these systems in real applications, polyvinylpirrolidone (PVP) was chosen due to the characteristics of non-toxicity, biocompatibility, and feasibility of this polymer to form complexes with many cations and chemical species. This approach allows the use of these materials in medicine and food, textile, or pharmaceutical industry. The functionalization process required a previous attachment of an active group on the surface of the nanoparticles. Subsequently, a polymer chain was generated in situ, using vinyltrimethoxysilane (VTMS) and 1-vinyl-2-pyrrolidone (VP) as reactives. The morphology and topology of the nanocompound has been characterized in aqueous suspensions, attending to possible applications in this medium. The results obtained from the different techniques show that the polymer chain was successfully grafted to the nanoparticle surface, and allow an estimation of the size of the modified particle. Their electrical and conformational behavior have also been studied in different aqueous chemical environments.

Biocompatible Nanoengineering of Graphene based Materials for Sensor Applications

DEFF Research Database (Denmark)

Halder, Arnab

Personalized healthcare and diagnostics is one of the most active areas of research in both academia and industry. Point-of-care sensing devices for monitoring and regulating from simple ions to large complex molecules are essential in our everyday life. These simple and inexpensive devices permit...... for novel glucose biosensing. In the next step, the pre-synthesized biocompatible graphene was functionalized with a redox active molecule, ferrocene. The as synthesized redox active and biocompatible graphene was further functionalized with enzymes and used for glucose and cholesterol biosensing. Finally...

Carbon nanotubes as in vivo bacterial probes.

Science.gov (United States)

Bardhan, Neelkanth M; Ghosh, Debadyuti; Belcher, Angela M

2014-09-17

With the rise in antibiotic-resistant infections, non-invasive sensing of infectious diseases is increasingly important. Optical imaging, although safer and simpler, is less developed than other modalities such as radioimaging, due to low availability of target-specific molecular probes. Here we report carbon nanotubes (SWNTs) as bacterial probes for fluorescence imaging of pathogenic infections. We demonstrate that SWNTs functionalized using M13 bacteriophage (M13-SWNT) can distinguish between F'-positive and F'-negative bacterial strains. Moreover, through one-step modification, we attach an anti-bacterial antibody on M13-SWNT, making it easily tunable for sensing specific F'-negative bacteria. We illustrate detection of Staphylococcus aureus intramuscular infections, with ~3.4 × enhancement in fluorescence intensity over background. SWNT imaging presents lower signal spread ~0.08 × and higher signal amplification ~1.4 × , compared with conventional dyes. We show the probe offers greater ~5.7 × enhancement in imaging of S. aureus infective endocarditis. These biologically functionalized, aqueous-dispersed, actively targeted, modularly tunable SWNT probes offer new avenues for exploration of deeply buried infections.

Carbon nanotubes as in vivo bacterial probes

Science.gov (United States)

Bardhan, Neelkanth M.; Ghosh, Debadyuti; Belcher, Angela M.

2014-09-01

With the rise in antibiotic-resistant infections, non-invasive sensing of infectious diseases is increasingly important. Optical imaging, although safer and simpler, is less developed than other modalities such as radioimaging, due to low availability of target-specific molecular probes. Here we report carbon nanotubes (SWNTs) as bacterial probes for fluorescence imaging of pathogenic infections. We demonstrate that SWNTs functionalized using M13 bacteriophage (M13-SWNT) can distinguish between F‧-positive and F‧-negative bacterial strains. Moreover, through one-step modification, we attach an anti-bacterial antibody on M13-SWNT, making it easily tunable for sensing specific F‧-negative bacteria. We illustrate detection of Staphylococcus aureus intramuscular infections, with ~3.4 × enhancement in fluorescence intensity over background. SWNT imaging presents lower signal spread ~0.08 × and higher signal amplification ~1.4 × , compared with conventional dyes. We show the probe offers greater ~5.7 × enhancement in imaging of S. aureus infective endocarditis. These biologically functionalized, aqueous-dispersed, actively targeted, modularly tunable SWNT probes offer new avenues for exploration of deeply buried infections.

Biocompatible and totally disintegrable semiconducting polymer for ultrathin and ultralightweight transient electronics.

Science.gov (United States)

Lei, Ting; Guan, Ming; Liu, Jia; Lin, Hung-Cheng; Pfattner, Raphael; Shaw, Leo; McGuire, Allister F; Huang, Tsung-Ching; Shao, Leilai; Cheng, Kwang-Ting; Tok, Jeffrey B-H; Bao, Zhenan

2017-05-16

Increasing performance demands and shorter use lifetimes of consumer electronics have resulted in the rapid growth of electronic waste. Currently, consumer electronics are typically made with nondecomposable, nonbiocompatible, and sometimes even toxic materials, leading to serious ecological challenges worldwide. Here, we report an example of totally disintegrable and biocompatible semiconducting polymers for thin-film transistors. The polymer consists of reversible imine bonds and building blocks that can be easily decomposed under mild acidic conditions. In addition, an ultrathin (800-nm) biodegradable cellulose substrate with high chemical and thermal stability is developed. Coupled with iron electrodes, we have successfully fabricated fully disintegrable and biocompatible polymer transistors. Furthermore, disintegrable and biocompatible pseudo-complementary metal-oxide-semiconductor (CMOS) flexible circuits are demonstrated. These flexible circuits are ultrathin (<1 μm) and ultralightweight (∼2 g/m 2 ) with low operating voltage (4 V), yielding potential applications of these disintegrable semiconducting polymers in low-cost, biocompatible, and ultralightweight transient electronics.

Biomolecular modification of zirconia surfaces for enhanced biocompatibility

Energy Technology Data Exchange (ETDEWEB)

Hsu, Shih-Kuang; Hsu, Hsueh-Chuan [Department of Dental Technology and Materials Science, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan, ROC (China); Ho, Wen-Fu [Department of Chemical and Materials Engineering, National University of Kaohsiung, Taiwan, ROC (China); Yao, Chun-Hsu [Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan, ROC (China); Chang, Pai-Ling [Taoyuan General Hospital, Taoyuan 33004, Taiwan, ROC (China); Wu, Shih-Ching, E-mail: scwu@ctust.edu.tw [Department of Dental Technology and Materials Science, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan, ROC (China)

2014-12-01

Yttria-tetragonal zirconia polycrystal (Y-TZP) is a preferred biomaterial due to its good mechanical properties. In order to improve the biocompatibility of zirconia, RGD-peptide derived from extracellular matrix proteins was employed to modify the surface of Y-TZP to promote cell adhesion in this study. The surface of Y-TZP specimens was first modified using a hydrothermal method for different lengths of time. The topographies of modified Y-TZP specimens were analyzed by contact angle, XRD, FTIR, AFM, and FE-SEM. The mechanical properties were evaluated using Vickers hardness and three point bending strength. Then, the RGD-peptide was immobilized on the surface of the Y-TZP by chemical treatment. These RGD-peptide immobilized Y-TZP specimens were characterized by FTIR and AFM, and then were cocultured with MG-63 osteoblast cells for biocompatibility assay. The cell morphology and proliferation were evaluated by SEM, WST-1, and ALP activity assay. The XRD results indicated that the phase transition, from tetragonal phase to monoclinic phase, was increased with a longer incubation time of hydrothermal treatment. However, there were no significant differences in mechanical strengths after RGD-peptide was successfully grafted onto the Y-TZP surface. The SEM images showed that the MG-63 cells appeared polygonal, spindle-shaped, and attached on the RGD-peptide immobilized Y-TZP. The proliferation and cellular activities of MG-63 cells on the RGD-peptide immobilized Y-TZP were better than that on the unmodified Y-TZP. From the above results, the RGD-peptide can be successfully grafted onto the hydrothermal modified Y-TZP surface. The RGD-peptide immobilized Y-TZP can increase cell adhesion, and thus, improve the biocompatibility of Y-TZP. - Highlights: • Covalent bonding between peptide and Y-TZP was proposed. • Stable biomimetic structures produced on the surface of zirconia. • The biocompatibility was improved.

Biocompatibility of Chitosan Carriers with Application in Drug Delivery

Directory of Open Access Journals (Sweden)

Ana Grenha

2012-09-01

Full Text Available Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures.

Mn-doped near-infrared quantum dots as multimodal targeted probes for pancreatic cancer imaging

Science.gov (United States)

Yong, Ken-Tye

2009-01-01

This work presents a novel approach to producing manganese (Mn)-doped quantum dots (Mnd-QDs) emitting in the near-infrared (NIR). Surface functionalization of Mnd-QDs with lysine makes them stably disperse in aqueous media and able to conjugate with targeting molecules. The nanoparticles were structurally and compositionally characterized and maintained a high photoluminescence quantum yield and displayed paramagnetism in water. The receptor-mediated delivery of bioconjugated Mnd-QDs into pancreatic cancer cells was demonstrated using the confocal microscopy technique. Cytotoxicity of Mnd-QDs on live cells has been evaluated. The NIR-emitting characteristic of the QDs has been exploited to acquire whole animal body imaging with high contrast signals. In addition, histological and blood analysis of mice have revealed that no long-term toxic effects arise from MnD-QDs. These studies suggest multimodal Mnd-QDs have the potentials as probes for early pancreatic cancer imaging and detection.

Biocompatibility of acrylic resin after being soaked in sodium hypochlorite

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Nike Hendrijatini

2009-06-01

Full Text Available Background: Acrylic resin as basic material for denture will stay on oral mucosa for a very long time. The polymerization of acrylic resin can be performed by conventional method and microwave, both produce different residual monomer at different toxicity. Acrylic resin can absorb solution, porous and possibly absorb disinfectantt as well, that may have toxic reaction with the tissue. Sodium Hypochlorite as removable denture disinfectant can be expected to be biocompatible to human body. The problem is how biocompatible acrylic resin which has been processed by conventional method and microwave method after being soaked in sodium hypochlorite solution. Purpose: The aim of this study was to understand in vitro biocompatibility of acrylic resin which has polimerated by conventional method and microwave after being soaked in sodium hypochlorite using tissue culture. Methods: Four groups of acrylic resin plate were produced, the first group was acrylic resin plate with microwave polymeration and soaked in sodium hypochlorite, the second group was acrylic resin plate with microwave polymeration but not soaked, the thirdwas one with conventional method and soaked and the last group was one with conventional method but not soaked, and in 1 control group. Each group consists of 7 plates. Biocompatibility test was performed in-vitro on each material using fibroblast tissue culture (BHK-21 cell-line. Result: The percentage between living cells and dead cells from materials which was given acrylic plate was wounted. The data was analyzed statistically with T test. Conclusion: The average value of living cells is higher in acrylic resin poimerization using microwave method compared to conventional method, in both soaked and non soaked (by sodium hypochlorite group. This means that sodium hypochlorite 0.5% was biocompatible to the mouth mucosa as removable denture disinfectant for 10 minutes soaking and washing afterwards.

Synthesis of biocompatible and highly photoluminescent nitrogen doped carbon dots from lime: Analytical applications and optimization using response surface methodology

Energy Technology Data Exchange (ETDEWEB)

Barati, Ali [Faculty of Chemistry, Institute for Advanced Studies in Basic Sciences, Zanjan (Iran, Islamic Republic of); Shamsipur, Mojtaba, E-mail: mshamsipur@yahoo.com [Department of Chemistry, Razi University, Kermanshah (Iran, Islamic Republic of); Arkan, Elham [Nano Drug Delivery Research Center Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Hosseinzadeh, Leila [Novel Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah (Iran, Islamic Republic of); Abdollahi, Hamid, E-mail: abd@iasbs.ac.ir [Faculty of Chemistry, Institute for Advanced Studies in Basic Sciences, Zanjan (Iran, Islamic Republic of)

2015-02-01

Herein, a facile hydrothermal treatment of lime juice to prepare biocompatible nitrogen-doped carbon quantum dots (N-CQDs) in the presence of ammonium bicarbonate as a nitrogen source has been presented. The resulting N-CQDs exhibited excitation and pH independent emission behavior; with the quantum yield (QY) up to 40%, which was several times greater than the corresponding value for CQDs with no added nitrogen source. The N-CQDs were applied as a fluorescent probe for the sensitive and selective detection of Hg{sup 2+} ions with a detection limit of 14 nM. Moreover, the cellular uptake and cytotoxicity of N-CQDs at different concentration ranges from 0.0 to 0.8 mg/ml were investigated by using PC12 cells as a model system. Response surface methodology was used for optimization and systematic investigation of the main variables that influence the QY, including reaction time, reaction temperature, and ammonium bicarbonate weight. - Highlights: • High fluorescent N-doped CQDs from lime juice have been prepared. • Response surface methodology was used to optimize and model the main factors. • N-doped CQDs were used in the selective and sensitive detection of Hg(II). • The biocompatibility of prepared N-doped CQDs was conformed using PC12 cells.

A new fluorescence/PET probe for targeting intracellular human telomerase reverse transcriptase (hTERT) using Tat peptide-conjugated IgM

International Nuclear Information System (INIS)

Jung, Kyung oh; Youn, Hyewon; Kim, Seung Hoo; Kim, Young-Hwa; Kang, Keon Wook; Chung, June-Key

2016-01-01

Despite an increasing need for methods to visualize intracellular proteins in vivo, the majority of antibody-based imaging methods available can only detect membrane proteins. The human telomerase reverse transcriptase (hTERT) is an intracellular target of great interest because of its high expression in several types of cancer. In this study, we developed a new probe for hTERT using the Tat peptide. An hTERT antibody (IgG or IgM) was conjugated with the Tat peptide, a fluorescence dye and "6"4Cu. HT29 (hTERT+) and U2OS (hTERT−) were used to visualize the intracellular hTERT. The hTERT was detected by RT-PCR and western blot. Fluorescence signals for hTERT were obtained by confocal microscopy, live cell imaging, and analyzed by Tissue-FAXS. In nude mice, tumors were visualized using the fluorescence imaging devices Maestro™ and PETBOX. In RT-PCR and western blot, the expression of hTERT was detected in HT29 cells, but not in U2OS cells. Fluorescence signals were clearly observed in HT29 cells and in U2OS cells after 1 h of treatment, but signals were only detected in HT29 cells after 24 h. Confocal microscopy showed that 9.65% of U2OS and 78.54% of HT29 cells had positive hTERT signals. 3D animation images showed that the probe could target intranuclear hTERT in the nucleus. In mice models, fluorescence and PET imaging showed that hTERT in HT29 tumors could be efficiently visualized. In summary, we developed a new method to visualize intracellular and intranuclear proteins both in vitro and in vivo. - Highlights: • We developed new probes for imaging hTERT using Tat-conjugated IgM antibodies labeled with a fluorescent dye and radioisotope. • This probes could be used to overcome limitation of conventional antibody imaging system in live cell imaging. • This system could be applicable to monitor intracellular and intranuclear proteins in vitro and in vivo.

A new fluorescence/PET probe for targeting intracellular human telomerase reverse transcriptase (hTERT) using Tat peptide-conjugated IgM

Energy Technology Data Exchange (ETDEWEB)

Jung, Kyung oh [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Biomedical Sciences, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Tumor Microenvironment Global Core Research Center, Seoul National University (Korea, Republic of); Youn, Hyewon, E-mail: hwyoun@snu.ac.kr [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Tumor Microenvironment Global Core Research Center, Seoul National University (Korea, Republic of); Cancer Imaging Center, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Seung Hoo [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Kim, Young-Hwa [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Biomedical Sciences, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Kang, Keon Wook [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Chung, June-Key, E-mail: jkchung@snu.ac.kr [Department of Nuclear Medicine, Seoul National University College of Medicine (Korea, Republic of); Biomedical Sciences, Seoul National University College of Medicine (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine (Korea, Republic of); Tumor Microenvironment Global Core Research Center, Seoul National University (Korea, Republic of)

2016-08-26

Despite an increasing need for methods to visualize intracellular proteins in vivo, the majority of antibody-based imaging methods available can only detect membrane proteins. The human telomerase reverse transcriptase (hTERT) is an intracellular target of great interest because of its high expression in several types of cancer. In this study, we developed a new probe for hTERT using the Tat peptide. An hTERT antibody (IgG or IgM) was conjugated with the Tat peptide, a fluorescence dye and {sup 64}Cu. HT29 (hTERT+) and U2OS (hTERT−) were used to visualize the intracellular hTERT. The hTERT was detected by RT-PCR and western blot. Fluorescence signals for hTERT were obtained by confocal microscopy, live cell imaging, and analyzed by Tissue-FAXS. In nude mice, tumors were visualized using the fluorescence imaging devices Maestro™ and PETBOX. In RT-PCR and western blot, the expression of hTERT was detected in HT29 cells, but not in U2OS cells. Fluorescence signals were clearly observed in HT29 cells and in U2OS cells after 1 h of treatment, but signals were only detected in HT29 cells after 24 h. Confocal microscopy showed that 9.65% of U2OS and 78.54% of HT29 cells had positive hTERT signals. 3D animation images showed that the probe could target intranuclear hTERT in the nucleus. In mice models, fluorescence and PET imaging showed that hTERT in HT29 tumors could be efficiently visualized. In summary, we developed a new method to visualize intracellular and intranuclear proteins both in vitro and in vivo. - Highlights: • We developed new probes for imaging hTERT using Tat-conjugated IgM antibodies labeled with a fluorescent dye and radioisotope. • This probes could be used to overcome limitation of conventional antibody imaging system in live cell imaging. • This system could be applicable to monitor intracellular and intranuclear proteins in vitro and in vivo.

Aligned ion implantation using scanning probes

International Nuclear Information System (INIS)

Persaud, A.

2006-01-01

A new technique for precision ion implantation has been developed. A scanning probe has been equipped with a small aperture and incorporated into an ion beamline, so that ions can be implanted through the aperture into a sample. By using a scanning probe the target can be imaged in a non-destructive way prior to implantation and the probe together with the aperture can be placed at the desired location with nanometer precision. In this work first results of a scanning probe integrated into an ion beamline are presented. A placement resolution of about 120 nm is reported. The final placement accuracy is determined by the size of the aperture hole and by the straggle of the implanted ion inside the target material. The limits of this technology are expected to be set by the latter, which is of the order of 10 nm for low energy ions. This research has been carried out in the context of a larger program concerned with the development of quantum computer test structures. For that the placement accuracy needs to be increased and a detector for single ion detection has to be integrated into the setup. Both issues are discussed in this thesis. To achieve single ion detection highly charged ions are used for the implantation, as in addition to their kinetic energy they also deposit their potential energy in the target material, therefore making detection easier. A special ion source for producing these highly charged ions was used and their creation and interactions with solids of are discussed in detail. (orig.)

Aligned ion implementation using scanning probes

Energy Technology Data Exchange (ETDEWEB)

Persaud, A

2006-12-12

A new technique for precision ion implantation has been developed. A scanning probe has been equipped with a small aperture and incorporated into an ion beamline, so that ions can be implanted through the aperture into a sample. By using a scanning probe the target can be imaged in a non-destructive way prior to implantation and the probe together with the aperture can be placed at the desired location with nanometer precision. In this work first results of a scanning probe integrated into an ion beamline are presented. A placement resolution of about 120 nm is reported. The final placement accuracy is determined by the size of the aperture hole and by the straggle of the implanted ion inside the target material. The limits of this technology are expected to be set by the latter, which is of the order of 10 nm for low energy ions. This research has been carried out in the context of a larger program concerned with the development of quantum computer test structures. For that the placement accuracy needs to be increased and a detector for single ion detection has to be integrated into the setup. Both issues are discussed in this thesis. To achieve single ion detection highly charged ions are used for the implantation, as in addition to their kinetic energy they also deposit their potential energy in the target material, therefore making detection easier. A special ion source for producing these highly charged ions was used and their creation and interactions with solids of are discussed in detail. (orig.)

A New Biocompatible and Antibacterial Phosphate Free Glass-Ceramic for Medical Applications

Science.gov (United States)

Cabal, Belén; Alou, Luís; Cafini, Fabio; Couceiro, Ramiro; Sevillano, David; Esteban-Tejeda, Leticia; Guitián, Francisco; Torrecillas, Ramón; Moya, José S.

2014-01-01

In the attempt to find valid alternatives to classic antibiotics and in view of current limitations in the efficacy of antimicrobial-coated or loaded biomaterials, this work is focused on the development of a new glass-ceramic with antibacterial performance together with safe biocompatibility. This bactericidal glass-ceramic composed of combeite and nepheline crystals in a residual glassy matrix has been obtained using an antimicrobial soda-lime glass as a precursor. Its inhibitory effects on bacterial growth and biofilm formation were proved against five biofilm-producing reference strains. The biocompatibility tests by using mesenchymal stem cells derived from human bone indicate an excellent biocompatibility. PMID:24961911

A New Biocompatible and Antibacterial Phosphate Free Glass-Ceramic for Medical Applications

Science.gov (United States)

Cabal, Belén; Alou, Luís; Cafini, Fabio; Couceiro, Ramiro; Sevillano, David; Esteban-Tejeda, Leticia; Guitián, Francisco; Torrecillas, Ramón; Moya, José S.

2014-06-01

In the attempt to find valid alternatives to classic antibiotics and in view of current limitations in the efficacy of antimicrobial-coated or loaded biomaterials, this work is focused on the development of a new glass-ceramic with antibacterial performance together with safe biocompatibility. This bactericidal glass-ceramic composed of combeite and nepheline crystals in a residual glassy matrix has been obtained using an antimicrobial soda-lime glass as a precursor. Its inhibitory effects on bacterial growth and biofilm formation were proved against five biofilm-producing reference strains. The biocompatibility tests by using mesenchymal stem cells derived from human bone indicate an excellent biocompatibility.

Biocompatible Synthetic and Semi-synthetic Polymers - A Patent Analysis.

Science.gov (United States)

Ranganathan, Balu; Miller, Charles; Sinskey, Anthony

2018-01-01

Bioengineering has come of ages by setting up spare parts manufacturing units to be used in human body such as invasive implants and interventional controlled drug delivery in vivo systems. As a matter of fact patients on basis of their fiscal strength have the option to undergo prophylactic tactical manoeuvre for longer life spans. In this sphere of invasive implants, biocompatible polymer implants are a state of the art cutting edge technology with outstanding innovations leading to number of very successful start-up companies with a plethora of patent portfolios. From 2000 onwards, patent filings and grants for biocompatible polymers are expanding. Currently definition of biocompatibility is quite ambiguous with respect to the use of FDA approved polymeric materials. This article analysed patent portfolios for the trend patterns of prolific biocompatible polymers for capitalization and commercialization in the forthcoming years. Pair Bulk Data (PBD) portal was used to mine patent portfolios. In this patent preliminary analysis report, patents from 2000 to 2015 were evaluated using 317(c) filings, grants and classifications data for poly(vinyl alcohol) (PVA), poly(glycolic acid) (PGA), poly(hydroxyalkanoates) (PHAs) and poly(lactic acid) (PLA). This patent portfolio preliminary analysis embarks into patent analysis for New Product Development (NPD) for corporate R&D investment managerial decisions and on government advocacy for federal funding which is decisive for developmental advances. An in-depth patent portfolio investigation with return of investment (RoI) is in the pipeline. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

DENTAL MATERIAL BIOCOMPATIBILITY: A CROSS-SECTIONAL STUDY

Directory of Open Access Journals (Sweden)

Carmen SAVIN

2017-06-01

Full Text Available The aim of this study is to assess the knowledge of the students in the Faculty of Dental Medicine of Iasi on the biocompatibility of the dental materials used in current practice. To this end, we elaborated our own questionnaire, including 10 questions to which 92 students from the last 2 years of study answered. The questionnaire cotains assertions on the potential toxic reactions of the most frequently used dental materials. The students answered correctly to the questions related to the biocompatibility of certain dental materials, such as glass-ionomer cement and calcium hydroxide, and they recognized that allergic reactions determined by acrylic resins may occur. We also noticed the lack of knowledge referring to the irreversible modifications produced by the tooth whitening substances on the enamel and dentin, as well as to the side effects produced by dental amalgam.

Physicochemical characterization and biocompatibility of alginate-polycation microcapsules designed for islet transplantation

Science.gov (United States)

Tam, Susan Kimberly

Microencapsulation represents a method for immunoprotecting transplanted therapeutic cells or tissues from graft rejection using a physical barrier. This approach is advantageous in that it eliminates the need to induce long-term immunosuppression and allows the option of transplanting non-cadaveric cell sources, such as animal cells and stem cell-derived tissues. The microcapsules that we have investigated are designed to immunoprotect islets of Langerhans (i.e. clusters of insulin-secreting cells), with the goal of treating insulin-dependent diabetes. With the aid of techniques for physicochemical analysis, this research focused on understanding which properties of the microcapsule are the most important for determining its biocompatibility. The objective of this work was to elucidate correlations between the chemical make-up, physicochemical properties, and in vivo biocompatibility of alginate-based microcapsules. Our approach was based on the hypothesis that the immune response to the microcapsules is governed by, and can therefore be controlled by, specific physicochemical properties of the microcapsule and its material components. The experimental work was divided into five phases, each associated with a specific aim : (1) To prove that immunoglobulins adsorb to the surface of alginate-polycation microcapsules, and to correlate this adsorption with the microcapsule chemistry. (2) To test interlaboratory reproducibility in making biocompatible microcapsules, and evaluate the suitability of our materials and fabrication protocols for subsequent studies. (3) To determine which physicochemical properties of alginates affect the in vivo biocompatibility of their gels. (4) To determine which physiochemical properties of alginate-polycation microcapsules are most important for determining their in vivo biocompatibility (5) To determine whether a modestly immunogenic membrane hinders or helps the ability of the microcapsule to immunoprotect islet xenografts in

[Study on biocompatibility of MIM 316L stainless steel].

Science.gov (United States)

Wang, Guohui; Zhu, Shaihong; Li, Yiming; Zhao, Yanzhong; Zhou, Kechao; Huang, Boyun

2007-04-01

This study was aimed to evaluate the biocompatibility of metal powder injection molding (MIM) 316L stainless steel. The percentage of S-period cells was detected by flow cytometry after L929 cells being incubated with extraction of MIM 316L stainless steel, and titanium implant materials for clinical application were used as control. In addition, both materials were implanted in animals and the histopathological evaluations were carried out. The statistical analyses show that there are no significant differences between the two groups (P > 0.05), which demonstrate that MIM 316L stainless steel has good biocompatibility.

Graphical representation of ribosomal RNA probe accessibility data using ARB software package

Directory of Open Access Journals (Sweden)

Amann Rudolf

2005-03-01

Full Text Available Abstract Background Taxon specific hybridization probes in combination with a variety of commonly used hybridization formats nowadays are standard tools in microbial identification. A frequently applied technology, fluorescence in situ hybridization (FISH, besides single cell identification, allows the localization and functional studies of the microbial community composition. Careful in silico design and evaluation of potential oligonucleotide probe targets is therefore crucial for performing successful hybridization experiments. Results The PROBE Design tools of the ARB software package take into consideration several criteria such as number, position and quality of diagnostic sequence differences while designing oligonucleotide probes. Additionally, new visualization tools were developed to enable the user to easily examine further sequence associated criteria such as higher order structure, conservation, G+C content, transition-transversion profiles and in situ target accessibility patterns. The different types of sequence associated information (SAI can be visualized by user defined background colors within the ARB primary and secondary structure editors as well as in the PROBE Match tool. Conclusion Using this tool, in silico probe design and evaluation can be performed with respect to in situ probe accessibility data. The evaluation of proposed probe targets with respect to higher-order rRNA structure is of importance for successful design and performance of in situ hybridization experiments. The entire ARB software package along with the probe accessibility data is available from the ARB home page http://www.arb-home.de.

Grafting polyethylenimine with quinoline derivatives for targeted imaging of intracellular Zn2+ and logic gate operations

International Nuclear Information System (INIS)

Pan, Yi; Shi, Yupeng; Chen, Junying; Wong, Chap-Mo; Zhang, Heng; Li, Mei-Jin; Li, Cheuk-Wing; Yi, Changqing

2016-01-01

In this study, a highly sensitive and selective fluorescent Zn 2+ probe which exhibited excellent biocompatibility, water solubility, and cell-membrane permeability, was facilely synthesized in a single step by grafting polyethyleneimine (PEI) with quinoline derivatives. The primary amino groups in the branched PEI can increase water solubility and cell permeability of the probe PEIQ, while quinoline derivatives can specifically recognize Zn 2+ and reduce the potential cytotoxicity of PEI. Basing on fluorescence off-on mechanism, PEIQ demonstrated excellent sensing capability towards Zn 2+ in absolute aqueous solution, where a high sensitivity with a detection limit as low as 38.1 nM, and a high selectivity over competing metal ions and potential interfering amino acids, were achieved. Inspired by these results, elementary logic operations (YES, NOT and INHIBIT) have been constructed by employing PEIQ as the gate while Zn 2+ and EDTA as chemical inputs. Together with the low cytotoxicity and good cell-permeability, the practical application of PEIQ in living cell imaging was satisfactorily demonstrated, emphasizing its wide application in fundamental biology research. - Graphical abstract: The fluorescent Zn 2+ probe, PEIQ, is facilely synthesized by grafting PEI with 8-CAAQ, and demonstrated for the pratical applications in Zn 2+ imaging and implementation of molecular logic operations within biological cells. - Highlights: • PEIQ, fluorescent Zn 2+ probe, is synthesized by grafting PEI with quinoline derivatives. • PEIQ exhibits high sensitivity and selectivity in absolute aqueous solution. • PEIQ is biocompatible, water soluble, and cell-membrane permeable. • Elementary logic operations have been demonstrated for PEIQ/Zn 2+ /EDTA system. • The practical application of PEIQ in living cell imaging is demonstrated.

In vivo biocompatibility of porous silicon biomaterials for drug delivery to the heart.

Science.gov (United States)

Tölli, Marja A; Ferreira, Mónica P A; Kinnunen, Sini M; Rysä, Jaana; Mäkilä, Ermei M; Szabó, Zoltán; Serpi, Raisa E; Ohukainen, Pauli J; Välimäki, Mika J; Correia, Alexandra M R; Salonen, Jarno J; Hirvonen, Jouni T; Ruskoaho, Heikki J; Santos, Hélder A

2014-09-01

Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI. The local injection of THCPSi microparticles into the myocardium led to significant higher activation of inflammatory cytokine and fibrosis promoting genes compared to TOPSi micro and nanoparticles; however, both particles showed no significant effect on myocardial fibrosis at one week post-injection. Our results suggest that THCPSi and TOPSi micro and nanoparticles could be applied for cardiac delivery of therapeutic agents in the future, and the PSi biomaterials might serve as a promising platform for the specific treatment of heart diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Whole genome expression profiling using DNA microarray for determining biocompatibility of polymeric surfaces

DEFF Research Database (Denmark)

Stangegaard, Michael; Wang, Zhenyu; Kutter, Jörg Peter

2006-01-01

There is an ever increasing need to find surfaces that are biocompatible for applications like medical implants and microfluidics-based cell culture systems. The biocompatibility of five different surfaces with different hydrophobicity was determined using gene expression profiling as well as more...

Study of biocompatible and biological materials

CERN Document Server

Pecheva, Emilia

2017-01-01

The book gives an overview on biomineralization, biological, biocompatible and biomimetic materials. It reveals the use of biomaterials alone or in composites, how their performance can be improved by tailoring their surface properties by external factors and how standard surface modification techniques can be applied in the area of biomaterials to beneficially influence their growth on surfaces.

Biocompatibility of root filling pastes used in primary teeth.

Science.gov (United States)

Lima, C C B; Conde Júnior, A M; Rizzo, M S; Moura, R D; Moura, M S; Lima, M D M; Moura, L F A D

2015-05-01

To evaluate the biocompatibility of two pastes designed to fill the root canals of primary teeth. A study group of 54 mice received subcutaneous tissue implants of polyethylene tubes containing CTZ or calcium hydroxide paste or, as a negative control, empty tubes. Biocompatibility was evaluated on days 7, 21 and 63, yielding a total of nine groups of six animals each. Following the experimental intervals, the implant areas were removed and subjected to histologic processing. After the tissues were stained with HE and Masson trichrome, two pathologists performed a histologic analysis of the samples in a blinded manner. Collagen fibre formation, tissue thickness and inflammatory cell infiltration were analysed qualitatively. Quantitative morphometry was performed for the thickness, perimeter length and tissue area of the region in direct contact with the open tube. anova with the Tukey post-test and Kruskal-Wallis analysis followed by Dunn's post-test, with significance established as P tube decreased during the experimental periods in all groups. The CTZ and calcium hydroxide pastes demonstrated biocompatibility with subcutaneous tissue in this experimental model. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

In Vitro Biocompatibility of Endodontic Sealers Incorporating Antibacterial Nanoparticles

Directory of Open Access Journals (Sweden)

Itzhak Abramovitz

2012-01-01

Full Text Available The main cause of endodontic disease is bacteria. Disinfection is presently achieved by cleaning the root canal system prior to obturation. Following setting, root canal filling is devoid of any antibacterial effect. Endodontic sealers with antimicrobial properties yet biocompatible may enhance root canal therapy. For this purpose, quaternized polyethylenimine nanoparticles which are antibacterial polymers, biocompatible, nonvolatile, and stable may be used. The aim of the present study was to examine the impact of added QPEI on the cytotoxicity of AH Plus, Epiphany, and GuttaFlow endodontic sealers. The effect of these sealers on the proliferation of RAW 264.7 macrophage and L-929 fibroblast cell lines and on the production of TNFα from macrophages was examined. Cell vitality was evaluated using a colorimetric XTT assay. The presence of cytokines was determined by two-site ELISA. Results show that QPEI at 1% concentration does not impair the basic properties of the examined sealers in both macrophages and fibroblast cell lines. Incorporation of 1% QPEI into the sealers did not impair their biocompatibility. QPEI is a potential clinical candidate to improve antibacterial activity of sealers without increasing cytotoxicity.

Donated chemical probes for open science.

Science.gov (United States)

Müller, Susanne; Ackloo, Suzanne; Arrowsmith, Cheryl H; Bauser, Marcus; Baryza, Jeremy L; Blagg, Julian; Böttcher, Jark; Bountra, Chas; Brown, Peter J; Bunnage, Mark E; Carter, Adrian J; Damerell, David; Dötsch, Volker; Drewry, David H; Edwards, Aled M; Edwards, James; Elkins, Jon M; Fischer, Christian; Frye, Stephen V; Gollner, Andreas; Grimshaw, Charles E; IJzerman, Adriaan; Hanke, Thomas; Hartung, Ingo V; Hitchcock, Steve; Howe, Trevor; Hughes, Terry V; Laufer, Stefan; Li, Volkhart Mj; Liras, Spiros; Marsden, Brian D; Matsui, Hisanori; Mathias, John; O'Hagan, Ronan C; Owen, Dafydd R; Pande, Vineet; Rauh, Daniel; Rosenberg, Saul H; Roth, Bryan L; Schneider, Natalie S; Scholten, Cora; Singh Saikatendu, Kumar; Simeonov, Anton; Takizawa, Masayuki; Tse, Chris; Thompson, Paul R; Treiber, Daniel K; Viana, Amélia Yi; Wells, Carrow I; Willson, Timothy M; Zuercher, William J; Knapp, Stefan; Mueller-Fahrnow, Anke

2018-04-20

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de">https://openscienceprobes.sgc-frankfurt.dehttps://openscienceprobes.sgc-frankfurt.de/">/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project. © 2018, Müller et al.

Use of 16S rRNA-targeted oligonucleotide probes to investigate the distribution of sulphate-reducing bacteria in estuarine sediments.

Science.gov (United States)

Purdy, K J.; Nedwell, D B.; Embley, T M.; Takii, S

2001-07-01

The distribution of sulphate-reducing bacteria (SRBs) in three anaerobic sediments, one predominantly freshwater and low sulphate and two predominantly marine and high sulphate, on the River Tama, Tokyo, Japan, was investigated using 16S rRNA-targeted oligonucleotide probes. Hybridisation results and sulphate reduction measurements indicated that SRBs are a minor part of the bacterial population in the freshwater sediments. Only Desulfobulbus and Desulfobacterium were detected, representing 1.6% of the general bacterial probe signal. In contrast, the SRB community detected at the two marine-dominated sites was larger and more diverse, representing 10-11.4% of the bacterial signal and with Desulfobacter, Desulfovibrio, Desulfobulbus and Desulfobacterium detected. In contrast to previous reports our results suggest that Desulfovibrio may not always be the most abundant SRB in anaerobic sediments. Acetate-utilising Desulfobacter were the dominant SRB in the marine-dominated sediments, and Desulfobulbus and Desulfobacterium were active in low-sulphate sediments, where they may utilise electron acceptors other than sulphate.

The Lectin Pathway of Complement and Biocompatibility

DEFF Research Database (Denmark)

Hein, Estrid; Garred, Peter

2015-01-01

In modern health technologies the use of biomaterials in the form of stents, haemodialysis tubes, artificial implants, bypass circuits etc. is rapidly expanding. The exposure of synthetic, foreign surfaces to the blood and tissue of the host, calls for strict biocompatibility in respect to contac...

Biocompatibility of two experimental scaffolds for regenerative endodontics

Directory of Open Access Journals (Sweden)

Dephne Jack Xin Leong

2016-05-01

Full Text Available Objectives The biocompatibility of two experimental scaffolds for potential use in revascularization or pulp regeneration was evaluated. Materials and Methods One resilient lyophilized collagen scaffold (COLL, releasing metronidazole and clindamycin, was compared to an experimental injectable poly(lactic-co-glycolic acid scaffold (PLGA, releasing clindamycin. Human dental pulp stem cells (hDPSCs were seeded at densities of 1.0 × 104, 2.5 × 104, and 5.0 × 104. The cells were investigated by light microscopy (cell morphology, MTT assay (cell proliferation and a cytokine (IL-8 ELISA test (biocompatibility. Results Under microscope, the morphology of cells coincubated for 7 days with the scaffolds appeared healthy with COLL. Cells in contact with PLGA showed signs of degeneration and apoptosis. MTT assay showed that at 5.0 × 104 hDPSCs, COLL demonstrated significantly higher cell proliferation rates than cells in media only (control, p < 0.01 or cells co-incubated with PLGA (p < 0.01. In ELISA test, no significant differences were observed between cells with media only and COLL at 1, 3, and 6 days. Cells incubated with PLGA expressed significantly higher IL-8 than the control at all time points (p < 0.01 and compared to COLL after 1 and 3 days (p < 0.01. Conclusions The COLL showed superior biocompatibility and thus may be suitable for endodontic regeneration purposes.

High efficiency diffusion molecular retention tumor targeting.

Directory of Open Access Journals (Sweden)

Yanyan Guo

Full Text Available Here we introduce diffusion molecular retention (DMR tumor targeting, a technique that employs PEG-fluorochrome shielded probes that, after a peritumoral (PT injection, undergo slow vascular uptake and extensive interstitial diffusion, with tumor retention only through integrin molecular recognition. To demonstrate DMR, RGD (integrin binding and RAD (control probes were synthesized bearing DOTA (for (111 In(3+, a NIR fluorochrome, and 5 kDa PEG that endows probes with a protein-like volume of 25 kDa and decreases non-specific interactions. With a GFP-BT-20 breast carcinoma model, tumor targeting by the DMR or i.v. methods was assessed by surface fluorescence, biodistribution of [(111In] RGD and [(111In] RAD probes, and whole animal SPECT. After a PT injection, both probes rapidly diffused through the normal and tumor interstitium, with retention of the RGD probe due to integrin interactions. With PT injection and the [(111In] RGD probe, SPECT indicated a highly tumor specific uptake at 24 h post injection, with 352%ID/g tumor obtained by DMR (vs 4.14%ID/g by i.v.. The high efficiency molecular targeting of DMR employed low probe doses (e.g. 25 ng as RGD peptide, which minimizes toxicity risks and facilitates clinical translation. DMR applications include the delivery of fluorochromes for intraoperative tumor margin delineation, the delivery of radioisotopes (e.g. toxic, short range alpha emitters for radiotherapy, or the delivery of photosensitizers to tumors accessible to light.

Polynucleotide probes that target a hypervariable region of 16S rRNA genes to identify bacterial isolates corresponding to bands of community fingerprints.

Science.gov (United States)

Heuer, H; Hartung, K; Wieland, G; Kramer, I; Smalla, K

1999-03-01

Temperature gradient gel electrophoresis (TGGE) is well suited for fingerprinting bacterial communities by separating PCR-amplified fragments of 16S rRNA genes (16S ribosomal DNA [rDNA]). A strategy was developed and was generally applicable for linking 16S rDNA from community fingerprints to pure culture isolates from the same habitat. For this, digoxigenin-labeled polynucleotide probes were generated by PCR, using bands excised from TGGE community fingerprints as a template, and applied in hybridizations with dot blotted 16S rDNA amplified from bacterial isolates. Within 16S rDNA, the hypervariable V6 region, corresponding to positions 984 to 1047 (Escherichia coli 16S rDNA sequence), which is a subset of the region used for TGGE (positions 968 to 1401), best met the criteria of high phylogenetic variability, required for sufficient probe specificity, and closely flanking conserved priming sites for amplification. Removal of flanking conserved bases was necessary to enable the differentiation of closely related species. This was achieved by 5' exonuclease digestion, terminated by phosphorothioate bonds which were synthesized into the primers. The remaining complementary strand was removed by single-strand-specific digestion. Standard hybridization with truncated probes allowed differentiation of bacteria which differed by only two bases within the probe target site and 1.2% within the complete 16S rDNA. However, a truncated probe, derived from an excised TGGE band of a rhizosphere community, hybridized with three phylogenetically related isolates with identical V6 sequences. Only one of the isolates comigrated with the excised band in TGGE, which was shown to be due to identical sequences, demonstrating the utility of a combined TGGE and V6 probe approach.

Surface sampling concentration and reaction probe

Science.gov (United States)

Van Berkel, Gary J; Elnaggar, Mariam S

2013-07-16

A method of analyzing a chemical composition of a specimen is described. The method can include providing a probe comprising an outer capillary tube and an inner capillary tube disposed co-axially within the outer capillary tube, where the inner and outer capillary tubes define a solvent capillary and a sampling capillary in fluid communication with one another at a distal end of the probe; contacting a target site on a surface of a specimen with a solvent in fluid communication with the probe; maintaining a plug volume proximate a solvent-specimen interface, wherein the plug volume is in fluid communication with the probe; draining plug sampling fluid from the plug volume through the sampling capillary; and analyzing a chemical composition of the plug sampling fluid with an analytical instrument. A system for performing the method is also described.

Silver-gold core-shell nanoparticles containing methylene blue as SERS labels for probing and imaging of live cells

International Nuclear Information System (INIS)

Guo, X.; Guo, Z.; Jin, Y.; Liu, Z.; Zhang, W.; Huang, D.

2012-01-01

We report on silver-gold core-shell nanostructures that contain Methylene Blue (MB) at the gold/x96silver interface. They can be used as reporter molecules in surface-enhanced Raman scattering (SERS) labels. The labels are stable and have strong SERS activity. TEM imaging revealed that these nanoparticles display bright and dark stripe structures. In addition, these labels can act as probes that can be detected and imaged through the specific Raman signatures of the reporters. We show that such SERS probes can identify cellular structures due to enhanced Raman spectra of intrinsic cellular molecules measured in the local optical fields of the core-shell nanostructures. They also provide structural information on the cellular environment as demonstrated for these nanoparticles as new SERS-active and biocompatible substrates for imaging of live cells. (author)

Molecular Imaging of Cancer Using X-ray Computed Tomography with Protease Targeted Iodinated Activity-Based Probes.

Science.gov (United States)

Gaikwad, Hanmant K; Tsvirkun, Darya; Ben-Nun, Yael; Merquiol, Emmanuelle; Popovtzer, Rachela; Blum, Galia

2018-03-14

X-ray computed tomography (CT) is a robust, precise, fast, and reliable imaging method that enables excellent spatial resolution and quantification of contrast agents throughout the body. However, CT is largely inadequate for molecular imaging applications due mainly to its low contrast sensitivity that forces the use of large concentrations of contrast agents for detection. To overcome this limitation, we generated a new class of iodinated nanoscale activity-based probes (IN-ABPs) that sufficiently accumulates at the target site by covalently binding cysteine cathepsins that are exceptionally highly expressed in cancer. The IN-ABPs are comprised of a short targeting peptide selective to specific cathepsins, an electrophilic moiety that allows activity-dependent covalent binding, and tags containing dendrimers with up to 48 iodine atoms. IN-ABPs selectively bind and inhibit activity of recombinant and intracellular cathepsin B, L, and S. We compared the in vivo kinetics, biodistribution, and tumor accumulation of IN-ABPs bearing 18 and 48 iodine atoms each, and their control counterparts lacking the targeting moiety. Here we show that although both IN-ABPs bind specifically to cathepsins within the tumor and produce detectable CT contrast, the 48-iodine bearing IN-ABP was found to be optimal with signals over 2.1-fold higher than its nontargeted counterpart. In conclusion, this study shows the synthetic feasibility and potential utility of IN-ABPs as potent contrast agents that enable molecular imaging of tumors using CT.

Ascorbic acid prevents cellular uptake and improves biocompatibility of chitosan nanoparticles.

Science.gov (United States)

Elshoky, Hisham A; Salaheldin, Taher A; Ali, Maha A; Gaber, Mohamed H

2018-04-11

Chitosan nanoparticles have many applications, such as gene and drug delivery, due to their biocompatibility. Chitosan nanoparticles are currently produced by dissolution in acetic acid that affects the biocompatibility at acidic pH. Here, we synthesized and characterized chitosan (CS) and ascorbate chitosan (AsCS) nanoparticles and investigated their cytotoxic effects, internalization, and distribution in the human colon carcinoma cell line using confocal laser scanning microscopy (CLSM). The CS and AsCS nanoparticles were spherical with average particle sizes of 44±8.4nm and 87±13.6nm, respectively. CS nanoparticles were taken up by the cells and showed dose-dependent cytotoxicity. By contrast, AsCS nanoparticles were not internalized and showed no cytotoxicity. Therefore, AsCS nanoparticles are more biocompatible than CS nanoparticles and may be more suitable for extracellular drug delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

GeneChip microarrays-signal intensities, RNA concentrations and probe sequences

International Nuclear Information System (INIS)

Binder, Hans; Preibisch, Stephan

2006-01-01

GeneChip microarrays consist of hundreds of thousands of oligonucleotide probes. The transformation of their signal intensities into RNA transcript concentrations requires the knowledge of the response function of the measuring device. We analysed the 'apparatus' function of perfect match (PM) and mismatched (MM) oligonucleotide probes of GeneChip microarrays after changes of the target concentration using the results of a spiked-in experiment. In agreement with previous studies we found that a competitive two-species Langmuir-adsorption model describes the probe intensities well. Each PM and MM probe is characterized by two hybridization constants which specify the propensity of the probe to bind specific and non-specific transcripts. The affinity for non-specific hybridization is on average equal for PM and MM. The purine-pyrimidine asymmetry of base pair interaction strengths, however, causes a characteristic PM-MM intensity difference, the sign of which depends on the middle base of the probe. The affinity for specific hybridization of the PM exceeds that of the MM on average by nearly one order of magnitude because the central mismatched base only weakly contributes to the stability of the probe/target duplexes. For the first time we differentiate between the free energy parameters related to the 64 possible middle-triples of DNA/RNA oligomer duplexes with a central Watson-Crick pairing and a central mismatched pairing. Both the PM and MM probes respond to the concentration of specific transcripts, which can be estimated from the PM and MM probe intensities using the Langmuir-model. The analysis of the PM-MM intensity difference provides at least no loss of accuracy and precision of the estimated concentration compared with the PM-only estimates which in turn outperform the MM-only estimates. The results show that the processing of the PM-MM intensity difference requires the consideration of a background term due to non-specific hybridization, which is

Tantalum, Niobium and Titanium Coatings for Biocompatibility Improvement of Dental Implants

Directory of Open Access Journals (Sweden)

Vajihesadat Mortazavi

2007-01-01

Full Text Available Introduction: Metals have a wide range of applications in implant and prosthetic materials in dentistry.Corrosion resistance and biocompatibility of metals should be improved in order to utilizethem as biomaterials. The aim of this work was to prepare metallic coatings on 316L stainless steel dental implants, to evaluate the corrosion characteristics of the uncoated and metallic coated dentalimplants as an indication of biocompatibility and, to compare the effect of the type of the coatings on biocompatibility.Materials and Methods: In this in vitro evaluation, three types of metallic coatings including tantalum, niobium and titanium coatings were compared using a physical vapor deposition process on 316L stainless steel dental implants. Structural characterization techniques including X-ray diffraction, scanning electron microscopy and energy dispersive X-ray analysis were utilized to investigatethe microstructure and morphology of the coatings. Electrochemical potentiodynamic tests were performed in two types of physiological solutions at 37±1°C in order to determine and compare the corrosioncurrent density and corrosion potential characteristics. The mean values were statistically compared by ANOVA at a 95% level of confidence.Results: the findings showed that all of the three types of metallic coatings had a positive effect on improvement of the corrosion behavior. The coatings could increase the corrosion resistance of 316L stainless steel and this trend was independent of the type of physiological environment.Conclusion: The biocompatible metallic coatings could decrease the corrosion current density and is a distinct advantage for prevention of ion release. Decreasing ion release can improve the biocompatibility of the dental implant, and consequently can prevent tissue damage, tissue inflammation and irritation, and can also lead to obtaining a desirable histopathological response.

Biocompatible polymer microneedle for topical/dermal delivery of tranexamic acid.

Science.gov (United States)

A Machekposhti, S; Soltani, M; Najafizadeh, P; Ebrahimi, S A; Chen, P

2017-09-10

Recently-introduced biocompatible polymeric microneedles offer an efficient method for drug delivery. Tranexamic acid is a novel drug for treating melasma that is administered both locally and orally and inhibits excessive melanin via melanocyte. The tranexamic acid biocompatible polymer microneedle used in this study was fabricated from PVP and methacrylic acid, using the lithography method. The required mechanical strength to pierce skin was attained by optimizing the ratio of PVP to methacrylic acid. Acute dermal toxicity was done, and drug diffusion in skin layers was simulated by calculating the diffusion coefficient of tranexamic acid in interstitial fluid (plasma). The biocompatible polymer microneedle was fabricated at 60°C. Needles could sustain 0.6N that is enough to pierce stratum corneum. 34% of the released drug was locally effective and the rest permeated through the skin. The pyramidal polymer microneedle in this study was fully released in skin in approx. 7h. This polymer microneedle has no dermal toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Targets Fishing and Identification of Calenduloside E as Hsp90AB1: Design, Synthesis, and Evaluation of Clickable Activity-Based Probe

Science.gov (United States)

Wang, Shan; Tian, Yu; Zhang, Jing-Yi; Xu, Hui-Bo; Zhou, Ping; Wang, Min; Lu, Sen-Bao; Luo, Yun; Wang, Min; Sun, Gui-Bo; Xu, Xu-Dong; Sun, Xiao-Bo

2018-01-01

Calenduloside E (CE), a natural triterpenoid compound isolated from Aralia elata, can protect against ox-LDL-induced human umbilical vein endothelial cell (HUVEC) injury in our previous reports. However, the exact targets and mechanisms of CE remain elusive. For the sake of resolving this question, we designed and synthesized a clickable activity-based probe (CE-P), which could be utilized to fish the functional targets in HUVECs using a gel-based strategy. Based on the previous studies of the structure-activity relationship (SAR), we introduced an alkyne moiety at the C-28 carboxylic group of CE, which kept the protective and anti-apoptosis activity. Via proteomic approach, one of the potential proteins bound to CE-P was identified as Hsp90AB1, and further verification was performed by pure recombinant Hsp90AB1 and competitive assay. These results demonstrated that CE could bind to Hsp90AB1. We also found that CE could reverse the Hsp90AB1 decrease after ox-LDL treatment. To make our results more convincing, we performed SPR analysis and the affinity kinetic assay showed that CE/CE-P could bind to Hsp90AB1 in a dose-dependent manner. Taken together, our research showed CE could probably bind to Hsp90AB1 to protect the cell injury, which might provide the basis for the further exploration of its cardiovascular protective mechanisms. For the sake of resolving this question, we designed and synthesized a clickable activity-based probe (CE-P), which could be utilized to fish the functional targets in HUVECs using a gel-based strategy. PMID:29875664

Synthesis of microbial elastomers based on soybean oily acids. Biocompatibility studies

International Nuclear Information System (INIS)

Hazer, Derya Burcu; Hazer, Baki; Kaymaz, Figen

2009-01-01

Biocompatibility studies of the autoxidized and unoxidized unsaturated medium-long chain length (m-lcl) co-poly-3-hydroxyalkanoates (m-lclPHAs) derived from soya oily acids have been reported. Pseudomonas oleovorans was grown on a series of mixtures of octanoic acid (OA) and soya oily acids (Sy) with weight ratios of 20:80, 28:72 and 50:50 in order to obtain unsaturated m-lcl copolyesters coded PHO-Sy-2080, PHO-Sy-2872 and PHO-Sy-5050, respectively. The PHA films were obtained by solvent cast from CHCl 3 . They were all originally sticky and waxy except PHO-Sy-5050. Autoxidation of the unsaturated copolyester films was carried out on exposure to air at room temperature in order to obtain crosslinked polymers. They became a highly flexible elastomer after being autoxidized (about 40 days of autoxidation). The in vivo tissue reactions of the autoxidized PHAs were evaluated by subcutaneous implantation in rats. The rats appeared to be healthy throughout the implantation period. No symptom such as necrosis, abscess or tumorigenesis was observed in the vicinity of the implants. Retrieved materials varied in their physical appearance after 6 weeks of implantation. In vivo biocompatibility studies of the medical applications indicated that the microbial copolyesters obtained were all biocompatible and especially the PHOSy series of copolyesters had the highest biocompatibility among them.

Fluorescent water-Soluble Probes Based on Ammonium Cation Peg Substituted Perylenepisimides: Synthesis, Photophysical Properties, and Live Cell Images

Science.gov (United States)

Yang, Wei; Cai, Jiaxuan; Zhang, Shuchen; Yi, Xuegang; Gao, Baoxiang

2018-01-01

To synthesize perylenbisimides (PBI) fluorescent probes that will improve the water-soluble ability and the cytocompatibility, the synthesis and properties of fluorescent water-soluble probes based on dendritic ammonium cation polyethylene glycol (PEG) substituted perylenebisimides(GPDIs) are presented. As we expected, with increased ammonium cation PEG, the aggregation of the PBI in an aqueous solution is completely suppressed by the hydrophilic ammonium cation PEG groups. And the fluorescence quantum yield increases from 25% for GPDI-1 to 62% for GPDI-2. When incubated with Hela cells for 48 h, the viabilities are 71% (for GPDI-1) and 76% (for GPDI-2). Live cell imaging shows that these probes are efficiently internalized by HeLa cells. The study of the photophysical properties indicated increasing the ammonium cation PEG generation can increase the fluorescence quantum yield. Live cell imaging shows that with the ammonium cation PEG chains of perylenebisimides has high biocompatibility. The exceptionally low cytotoxicity is ascribed to the ammonium cation PEG chains, which protect the dyes from nonspecifically interacting with the extracellular proteins. Live cell imaging shows that ammonium cations PEG chains can promote the internalization of these probes.

Probing the photoluminescence properties of gold nanoclusters by fluorescence lifetime correlation spectroscopy

International Nuclear Information System (INIS)

Yuan, C. T.; Lin, T. N.; Shen, J. L.; Lin, C. A.; Chang, W. H.; Cheng, H. W.; Tang, J.

2013-01-01

Gold nanoclusters (Au NCs) have attracted much attention for promising applications in biological imaging owing to their tiny sizes and biocompatibility. So far, most efforts have been focused on the strategies for fabricating high-quality Au NCs and then characterized by conventional ensemble measurement. Here, a fusion single-molecule technique combining fluorescence correlation spectroscopy and time-correlated single-photon counting can be successfully applied to probe the photoluminescence (PL) properties for sparse Au NCs. In this case, the triplet-state dynamics and diffusion process can be observed simultaneously and the relevant time constants can be derived. This work provides a complementary insight into the PL mechanism at the molecular levels for Au NCs in solution

Synthesis, characterization and in vivo evaluation of biocompatible ferrogels

Energy Technology Data Exchange (ETDEWEB)

Lopez-Lopez, M.T., E-mail: modesto@ugr.es [Department of Applied Physics, University of Granada, Granada (Spain); Instituto de Investigación Biosanitaria ibs.GRANADA, Granada (Spain); Rodriguez, I.A. [Instituto de Investigación Biosanitaria ibs.GRANADA, Granada (Spain); Department of Histology (Tissue Engineering Group), University of Granada, Granada (Spain); Rodriguez-Arco, L. [Department of Applied Physics, University of Granada, Granada (Spain); Instituto de Investigación Biosanitaria ibs.GRANADA, Granada (Spain); Carriel, V. [Instituto de Investigación Biosanitaria ibs.GRANADA, Granada (Spain); Department of Histology (Tissue Engineering Group), University of Granada, Granada (Spain); Bonhome-Espinosa, A.B. [Department of Applied Physics, University of Granada, Granada (Spain); Instituto de Investigación Biosanitaria ibs.GRANADA, Granada (Spain); Campos, F. [Instituto de Investigación Biosanitaria ibs.GRANADA, Granada (Spain); Department of Histology (Tissue Engineering Group), University of Granada, Granada (Spain); Zubarev, A. [Department of Mathematical Physics, Ural Federal University, Ekaterinburg (Russian Federation); Duran, J.D.G. [Department of Applied Physics, University of Granada, Granada (Spain); Instituto de Investigación Biosanitaria ibs.GRANADA, Granada (Spain)

2017-06-01

A hydrogel is a 3-D network of polymer chains in which water is the dispersion medium. Hydrogels have found extensive applications in the biomedical field due to their resemblance to living tissues. Furthermore, hydrogels can be endowed with exceptional properties by addition of synthetic materials. For example, magnetic field-sensitive gels, called ferrogels, are obtained by embedding magnetic particles in the polymer network. Novel living tissues with unique magnetic field-sensitive properties were recently prepared by 3-D cell culture in biocompatible ferrogels. This paper critically reviews the most recent progress and perspectives in their synthesis, characterization and biocompatibility evaluation. Optimization of ferrogels for this novel application requires low-density, strongly magnetic, multi-domain particles. Interestingly, the rheological properties of the resulting ferrogels in the absence of field were largely enhanced with respect to nonmagnetic hydrogels, which can only be explained by the additional cross-linking imparted by the embedded magnetic particles. Remarkably, rheological measurements under an applied magnetic field demonstrated that ferrogels presented reversibly tunable mechanical properties, which constitutes a unique advantage with respect to nonmagnetic hydrogels. In vivo evaluation of ferrogels showed good biocompatibility, with only some local inflammatory response, and no particle migration or damage to distant organs.

MOTRIMS as a generalized probe of AMO processes

International Nuclear Information System (INIS)

Bredy, R.; Nguyen, H.; Camp, H.; Flechard, X.; De Paola, B.D.

2003-01-01

Magneto-optical trap recoil ion momentum spectroscopy (MOTRIMS) is one of the newest offshoots of the generalized TRIMS approach to ion-atom collisions. By using lasers instead of the more usual supersonic expansion to cool the target, MOTRIMS has demonstrated two distinct advantages over conventional TRIMS. The first is better resolution, now limited by detectors instead of target temperature. The second is its suitability for use in the study of laser-excited targets. In this presentation we will present a third advantage: The use of MOTRIMS as a general-purpose probe of AMO processes in cold atomic clouds of atoms and molecules. Specifically, the projectile ion beam can be used as a probe of processes as diverse as target dressing by femtosecond optical pulses, photo-association (laser-assisted cold collisions) photo-ionization, and electromagnetically-induced transparency. We will present data for the processes we have investigated, and speculations on what we expect to see for the processes we plan to investigate in the future

Identification of Cannabis sativa L. using the 1-kbTHCA synthase-fluorescence in situ hybridization probe.

Science.gov (United States)

Jeangkhwoa, Pattraporn; Bandhaya, Achirapa; Umpunjun, Puangpaka; Chuenboonngarm, Ngarmnij; Panvisavas, Nathinee

2017-03-01

This study reports a successful application of fluorescence in situ hybridization (FISH) technique in the identification of Cannabis sativa L. cells recovered from fresh and dried powdered plant materials. Two biotin-16-dUTP-labeled FISH probes were designed from the Cannabis-specific tetrahydrocannabinolic acid synthase (THCAS) gene and the ITS region of the 45S rRNA gene. Specificity of probe-target hybridization was tested against the target and 4 non-target plant species, i.e., Humulus lupulus, Mitragyna speciosa, Papaver sp., and Nicotiana tabacum. The 1-kb THCA synthase hybridization probe gave Cannabis-specific hybridization signals, unlike the 700-bp Cannabis-ITS hybridization probe. Probe-target hybridization was also confirmed against 20 individual Cannabis plant samples. The 1-kb THCA synthase and 700-bp Cannabis-ITS hybridization probes clearly showed 2 hybridization signals per cell with reproducibility. The 1-kb THCA synthase probe did not give any FISH signal when tested against H. lupulus, its closely related member of the Canabaceae family. It was also showed that 1-kb THCA synthase FISH probe can be applied to identify small amount of dried powdered Cannabis material with an addition of rehydration step prior to the experimental process. This study provided an alternative identification method for Cannabis trace. Copyright © 2016. Published by Elsevier B.V.

A green chemistry approach for synthesizing biocompatible gold nanoparticles

Science.gov (United States)

Gurunathan, Sangiliyandi; Han, JaeWoong; Park, Jung Hyun; Kim, Jin-Hoi

2014-05-01

Gold nanoparticles (AuNPs) are a fascinating class of nanomaterial that can be used for a wide range of biomedical applications, including bio-imaging, lateral flow assays, environmental detection and purification, data storage, drug delivery, biomarkers, catalysis, chemical sensors, and DNA detection. Biological synthesis of nanoparticles appears to be simple, cost-effective, non-toxic, and easy to use for controlling size, shape, and stability, which is unlike the chemically synthesized nanoparticles. The aim of this study was to synthesize homogeneous AuNPs using pharmaceutically important Ganoderma spp . We developed a simple, non-toxic, and green method for water-soluble AuNP synthesis by treating gold (III) chloride trihydrate (HAuCl4) with a hot aqueous extract of the Ganoderma spp . mycelia. The formation of biologically synthesized AuNPs (bio-AuNPs) was characterized by ultraviolet (UV)-visible absorption spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDX), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Furthermore, the biocompatibility of as-prepared AuNPs was evaluated using a series of assays, such as cell viability, lactate dehydrogenase leakage, and reactive oxygen species generation (ROS) in human breast cancer cells (MDA-MB-231). The color change of the solution from yellow to reddish pink and strong surface plasmon resonance were observed at 520 nm using UV-visible spectroscopy, and that indicated the formation of AuNPs. DLS analysis revealed the size distribution of AuNPs in liquid solution, and the average size of AuNPs was 20 nm. The size and morphology of AuNPs were investigated using TEM. The biocompatibility effect of as-prepared AuNPs was investigated in MDA-MB-231 breast cancer cells by using various concentrations of AuNPs (10 to 100 μM) for 24 h. Our findings suggest that AuNPs are non-cytotoxic and biocompatible. To the best of our knowledge

Biocompatibility and Toxicity of Nano biomaterials 2014

International Nuclear Information System (INIS)

Li, X.; Lee, S.Ch.; Zhang, Sh.; Akasaka, T.

2014-01-01

It is well known that nano materials have developed rapidly over the past few decades. Based on their unique physicochemical properties and special mechanical properties, nano materials have provided application possibility in many different fields. Currently, as nano biomaterials, they are widely used in various biomedical applications, such as drug delivery systems, tissue engineering, dental/bone implant, and biosensors. For example, nano biomaterials have been used in tissue engineering because of their satisfactory bioactivity, high mechanical properties, and large surface area to adsorb specific proteins. Many kinds of nano biomaterials are used to prepare composite scaffolds to get better biocompatibility and higher ability in repairing specific tissues. Several antibacterial metallic nano biomaterials are used to coat implant surfaces to improve the speed of healing fractures. In addition, lots of nano biomaterials have the potential to break the limitations of the traditional delivery systems. They can load larger amount of drugs and provide stable drug release for long time at the targeted sites, such as tumors. Moreover, they can combine with polymers to furnish simultaneous drug delivery systems with the controllable release rate. Besides these applications, more and more nano biomaterials show great potential to be applied as highly sensitive biosensors because they have higher ability in loading firmly or interacting completely with recognition aptamers.

Dramatically improved RNA in situ hybridization signals using LNA-modified probes

DEFF Research Database (Denmark)

Thomsen, Rune; Nielsen, Peter Stein; Jensen, Torben Heick

2005-01-01

. This increases the thermal stability of hybrids formed with RNA. The LNA-based probes detect specific RNAs in fixed yeast cells with an efficiency far better than conventional DNA oligonucleotide probes of the same sequence. Using this probe design, we were also able to detect poly(A)+ RNA accumulation within......In situ detection of RNA by hybridization with complementary probes is a powerful technique. Probe design is a critical parameter in successful target detection. We have evaluated the efficiency of fluorescent DNA oligonucleotides modified to contain locked nucleic acid (LNA) residues...

Sandwich hybridization probes for the detection of Pseudo-nitzschia (Bacillariophyceae) species: An update to existing probes and a description of new probes.

Science.gov (United States)

Bowers, Holly A; Marin, Roman; Birch, James M; Scholin, Christopher A

2017-12-01

New sandwich hybridization assay (SHA) probes for detecting Pseudo-nitzschia species (P. arenysensis, P. fraudulenta, P. hasleana, P. pungens) are presented, along with updated cross-reactivity information on historical probes (SHA and FISH; fluorescence in situ hybridization) targeting P. australis and P. multiseries. Pseudo-nitzschia species are a cosmopolitan group of diatoms that produce varying levels of domoic acid (DA), a neurotoxin that can accumulate in finfish and shellfish and transfer throughout the food web. Consumption of infected food sources can lead to illness in humans (amnesic shellfish poisoning; ASP) and marine wildlife (domoic acid poisoning; DAP). The threat of human illness, along with economic loss from fishery closures has resulted in the implementation of monitoring protocols and intensive ecological studies. SHA probes have been instrumental in some of these efforts, as the technique performs well in complex heterogeneous sample matrices and has been adapted to benchtop and deployable (Environmental Sample Processor) platforms. The expanded probe set will enhance future efforts towards understanding spatial, temporal and successional patterns in species during bloom and non-bloom periods. Copyright © 2017 Elsevier B.V. All rights reserved.

In vivo type 2 cannabinoid receptor-targeted tumor optical imaging using a near infrared fluorescent probe.

Science.gov (United States)

Zhang, Shaojuan; Shao, Pin; Bai, Mingfeng

2013-11-20

The type 2 cannabinoid receptor (CB2R) plays a vital role in carcinogenesis and progression and is emerging as a therapeutic target for cancers. However, the exact role of CB2R in cancer progression and therapy remains unclear. This has driven the increasing efforts to study CB2R and cancers using molecular imaging tools. In addition, many types of cancers overexpress CB2R, and the expression levels of CB2R appear to be associated with tumor aggressiveness. Such upregulation of the receptor in cancer cells provides opportunities for CB2R-targeted imaging with high contrast and for therapy with low side effects. In the present study, we report the first in vivo tumor-targeted optical imaging using a novel CB2R-targeted near-infrared probe. In vitro cell fluorescent imaging and a competitive binding assay indicated specific binding of NIR760-mbc94 to CB2R in CB2-mid delayed brain tumor (DBT) cells. NIR760-mbc94 also preferentially labeled CB2-mid DBT tumors in vivo, with a 3.7-fold tumor-to-normal contrast enhancement at 72 h postinjection, whereas the fluorescence signal from the tumors of the mice treated with NIR760 free dye was nearly at the background level at the same time point. SR144528, a CB2R competitor, significantly inhibited tumor uptake of NIR760-mbc94, indicating that NIR760-mbc94 binds to CB2R specifically. In summary, NIR760-mbc94 specifically binds to CB2R in vitro and in vivo and appears to be a promising molecular tool that may have great potential for use in diagnostic imaging of CB2R-positive cancers and therapeutic monitoring as well as in elucidating the role of CB2R in cancer progression and therapy.

Study of a Laser-Produced Plasma by Langmuir Probes

DEFF Research Database (Denmark)

Chang, C. T.; Hasimi, M.; Pant, H. C.

1977-01-01

-emission peak and the main plasma from the target. The flow velocity, density and electron temperature of the plasma were determined. The expansion of the plasma was found to be adiabatic, yielding gamma =5/3. The spatial distribution of the plasma was observed to be strongly anisotropic.......The structure, the parameters and the expansion of the plasma produced by focusing a 7 J, 20 ns Nd-glass laser on stainless-steel and glass targets suspended in a high-vacuum chamber were investigated by Langmuir probes. It was observed that the probe signals consisted of a photoelectric...

Grafting polyethylenimine with quinoline derivatives for targeted imaging of intracellular Zn{sup 2+} and logic gate operations

Energy Technology Data Exchange (ETDEWEB)

Pan, Yi; Shi, Yupeng; Chen, Junying; Wong, Chap-Mo; Zhang, Heng [Key Laboratory of Sensing Technology and Biomedical Instruments (Guangdong Province), School of Engineering, Sun Yat-Sen University, Guangzhou (China); Li, Mei-Jin [Key Laboratory of Analysis and Detection Technology for Food Safety, Ministry of Education and Fujian Province, Department of Chemistry, Fuzhou University, Fuzhou (China); Li, Cheuk-Wing [Institute of Chinese Medical Sciences, University of Macau (China); Yi, Changqing, E-mail: yichq@mail.sysu.edu.cn [Key Laboratory of Sensing Technology and Biomedical Instruments (Guangdong Province), School of Engineering, Sun Yat-Sen University, Guangzhou (China); Research Institute of Sun Yat-Sen University in Shenzhen, Shenzhen (China)

2016-12-01

In this study, a highly sensitive and selective fluorescent Zn{sup 2+} probe which exhibited excellent biocompatibility, water solubility, and cell-membrane permeability, was facilely synthesized in a single step by grafting polyethyleneimine (PEI) with quinoline derivatives. The primary amino groups in the branched PEI can increase water solubility and cell permeability of the probe PEIQ, while quinoline derivatives can specifically recognize Zn{sup 2+} and reduce the potential cytotoxicity of PEI. Basing on fluorescence off-on mechanism, PEIQ demonstrated excellent sensing capability towards Zn{sup 2+} in absolute aqueous solution, where a high sensitivity with a detection limit as low as 38.1 nM, and a high selectivity over competing metal ions and potential interfering amino acids, were achieved. Inspired by these results, elementary logic operations (YES, NOT and INHIBIT) have been constructed by employing PEIQ as the gate while Zn{sup 2+} and EDTA as chemical inputs. Together with the low cytotoxicity and good cell-permeability, the practical application of PEIQ in living cell imaging was satisfactorily demonstrated, emphasizing its wide application in fundamental biology research. - Graphical abstract: The fluorescent Zn{sup 2+} probe, PEIQ, is facilely synthesized by grafting PEI with 8-CAAQ, and demonstrated for the pratical applications in Zn{sup 2+} imaging and implementation of molecular logic operations within biological cells. - Highlights: • PEIQ, fluorescent Zn{sup 2+} probe, is synthesized by grafting PEI with quinoline derivatives. • PEIQ exhibits high sensitivity and selectivity in absolute aqueous solution. • PEIQ is biocompatible, water soluble, and cell-membrane permeable. • Elementary logic operations have been demonstrated for PEIQ/Zn{sup 2+}/EDTA system. • The practical application of PEIQ in living cell imaging is demonstrated.

Bioinspired, Ultrastrong, Highly Biocompatible, and Bioactive Natural Polymer/Graphene Oxide Nanocomposite Films.

Science.gov (United States)

Zhu, Wen-Kun; Cong, Huai-Ping; Yao, Hong-Bin; Mao, Li-Bo; Asiri, Abdullah M; Alamry, Khalid A; Marwani, Hadi M; Yu, Shu-Hong

2015-09-09

Tough and biocompatible nanocomposite films: A new type of bioinspired ultrastrong, highly biocompatible, and bioactive konjac glucomannan (KGM)/graphene oxide (GO) nanocomposite film is fabricated on a large scale by a simple solution-casting method. Such KGM-GO composite films exhibit much enhanced mechanical properties under the strong hydrogen-bonding interactions, showing great potential in the fields of tissue engineering and food package. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biocompatibility of photopolymers for additive manufacturing

OpenAIRE

Leonhardt Stefan; Klare Martin; Scheer Maurice; Fischer Theresa; Cordes Burghard; Eblenkamp Markus

2016-01-01

To establish photopolymers for the production of class II or class III medical products by additive manufacturing it is essential to know which components of photopolymeric systems, consisting of monomers, photoinitiators and additives, are the determining factors on their biocompatible properties. In this study the leachable substances of a cured photopolymeric system were eluted and identified by HPLC-MS detection. In addition the cured photopolymer was testes for cytotoxicity and genotoxic...

Folate receptor targeting silica nanoparticle probe for two-photon fluorescence bioimaging

Science.gov (United States)

Wang, Xuhua; Yao, Sheng; Ahn, Hyo-Yang; Zhang, Yuanwei; Bondar, Mykhailo V.; Torres, Joseph A.; Belfield, Kevin D.

2010-01-01

Narrow dispersity organically modified silica nanoparticles (SiNPs), diameter ~30 nm, entrapping a hydrophobic two-photon absorbing fluorenyl dye, were synthesized by hydrolysis of triethoxyvinylsilane and (3-aminopropyl)triethoxysilane in the nonpolar core of Aerosol-OT micelles. The surface of the SiNPs were functionalized with folic acid, to specifically deliver the probe to folate receptor (FR) over-expressing Hela cells, making these folate two-photon dye-doped SiNPs potential candidates as probes for two-photon fluorescence microscopy (2PFM) bioimaging. In vitro studies using FR over-expressing Hela cells and low FR expressing MG63 cells demonstrated specific cellular uptake of the functionalized nanoparticles. One-photon fluorescence microscopy (1PFM) imaging, 2PFM imaging, and two-photon fluorescence lifetime microscopy (2P-FLIM) imaging of Hela cells incubated with folate-modified two-photon dye-doped SiNPs were demonstrated. PMID:21258480

Hydrothermal Synthesis and Biocompatibility Study of Highly Crystalline Carbonated Hydroxyapatite Nanorods

Science.gov (United States)

Xue, Caibao; Chen, Yingzhi; Huang, Yongzhuo; Zhu, Peizhi

2015-08-01

Highly crystalline carbonated hydroxyapatite (CHA) nanorods with different carbonate contents were synthesized by a novel hydrothermal method. The crystallinity and chemical structure of synthesized nanorods were studied by Fourier transform infrared spectroscopy (FTIR), X-ray photo-electronic spectroscopy (XPS), X-ray diffraction (XRD), Raman spectroscopy, and transmission electron microscopy (TEM). The biocompatibility of synthesized CHA nanorods was evaluated by cell viability and alkaline phosphatase (ALP) activity of MG-63 cell line. The biocompatibility evaluation results show that these CHA nanorods are biologically active apatites and potentially promising bone-substitute biomaterials for orthopedic application.

Synthesis and characterization of an MRI Gd-based probe designed to target the translocator protein

International Nuclear Information System (INIS)

Cerutti, Erika; Aime, Silvio; Damont, Annelaure; Dolle, Frederic; Baroni, Simona

2013-01-01

DPA-713 is the lead compound of a recently reported pyrazolo[1,5-a]pyrimidine acetamide series, targeting the translocator protein (TSPO 18 kDa), and as such, this structure, as well as closely related derivatives, have been already successfully used as positron emission tomography radioligands. On the basis of the pharmacological core of this ligands series, a new magnetic resonance imaging probe, coded DPA-C6-(Gd)DOTAMA was designed and successfully synthesized in six steps and 13% overall yield from DPA-713. The Gd-DOTA monoamide cage (DOTA = 1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid) represents the magnetic resonance imaging reporter, which is spaced from the phenyl-pyrazolo[1,5-a]pyrimidine acetamide moiety (DPA-713 motif) by a six carbon-atom chain. DPA-C6-(Gd)DOTAMA relaxometric characterization showed the typical behavior of a small-sized molecule (relaxivity value: 6.02 mM -1 s -1 at 20 MHz). The good hydrophilicity of the metal chelate makes DPAC6-(Gd)DOTAMA soluble in water, affecting thus its biodistribution with respect to the parent lipophilic DPA-713 molecule. For this reason, it was deemed of interest to load the probe to a large carrier in order to increase its residence lifetime in blood. Whereas DPA-C6-(Gd)DOTAMA binds to serum albumin with a low affinity constant, it can be entrapped into liposomes (both in the membrane and in the inner aqueous cavity). The stability of the supramolecular adduct formed by the Gd-complex and liposomes was assessed by a competition test with albumin. (authors)

Perceiving the vertical distances of surfaces by means of a hand-held probe.

Science.gov (United States)

Chan, T C; Turvey, M T

1991-05-01

Nine experiments were conducted on the haptic capacity of people to perceive the distances of horizontal surfaces solely on the basis of mechanical stimulation resulting from contacting the surfaces with a vertically held rod. Participants touched target surfaces with rods inside a wooden cabinet and reported the perceived surface location with an indicator outside the cabinet. The target surface, rod, and the participant's hand were occluded, and the sound produced in exploration was muffled. Properties of the probe (length, mass, moment of inertia, center of mass, and shape) were manipulated, along with surface distance and the method and angle of probing. Results suggest that for the most common method of probing, namely, tapping, perceived vertical distance is specific to a particular relation among the rotational inertia of the probe, the distance of the point of contact with the surface from the probe's center of percussion, and the inclination at contact of the probe to the surface. They also suggest that the probe length and the distance probed are independently perceivable. The results were discussed in terms of information specificity versus percept-percept coupling and parallels between selective attention in haptic and visual perception.

Ultrasound-assisted fabrication of a biocompatible magnetic hydroxyapatite.

Science.gov (United States)

Zhou, Gang; Song, Wei; Hou, Yongzhao; Li, Qing; Deng, Xuliang; Fan, Yubo

2014-10-01

This work describes the fabrication and characterization of a biocompatible magnetic hydroxyapatite (HA) using an ultrasound-assisted co-precipitation method. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM) were used to characterize the structure and chemical composition of the produced samples. The M-H loops of synthesized materials were traced using a vibrating sample magnetometer (VSM) and the biocompatibility was evaluated by cell culture and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Furthermore, in vivo histopathological examinations were used to evaluate the potential toxicological effects of Fe₃O₄-HA composites on kidney of SD rats injected intraperitoneally with Fe₃O₄-HA particles. The results showed that magnetic iron oxide particles first replace OH ions of HA, which are parallel to the c axis, and then enter the HA crystal lattice which produces changes in the crystal surface of HA. Chemical bond interaction was observed between PO₄³⁻ groups of HA and iron ions of Fe₃O₄. The saturation magnetization (MS ) of Fe₃O₄-HA composites was 46.36 emu/g obtained from VSM data. Cell culture and MTT assays indicated that HA could affect the growth and proliferation of HEK-293 cells. This Fe₃O₄-HA composite produced no negative effects on cell morphology, viability, and proliferation and exhibited remarkable biocompatibility. Moreover, no inflammatory cell infiltration was observed in kidney histopathology slices. Therefore, this study succeeds to develop a Fe₃O₄-HA composite as a prospective biomagnetic material for future applications. © 2013 Wiley Periodicals, Inc.

Zirconium phosphate nanoplatelets: a biocompatible nanomaterial for drug delivery to cancer

Science.gov (United States)

Saxena, Vipin; Diaz, Agustin; Clearfield, Abraham; Batteas, James D.; Hussain, Muhammad Delwar

2013-02-01

The objective of this study was to evaluate the biocompatibility of zirconium phosphate (ZrP) nanoplatelets (NPs), and their use in drug delivery. ZrP and doxorubicin-intercalated ZrP (DOX:ZrP) NPs were characterized by using X-Ray Powder Diffraction (XRPD), Thermogravimetric Analysis (TGA), Transmission Electron Micrography (TEM), Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM). Biocompatibility of ZrP NPs was evaluated in human embryonic kidney (HEK-293), breast cancer (MCF-7), metastatic breast cancer (MDA-MB-231), ovarian cancer (OVCAR-3), resistant cancer (NCI-RES/ADR) cells and mouse macrophage (RAW 264.7) cell lines. Hemocompatibility of ZrP NPs was evaluated with human red blood cells. Simulated body fluid (SBF) of pH 7.4 was used to determine the in vitro release of doxorubicin from DOX:ZrP NPs. Cellular uptake and in vitro cytotoxicity studies of DOX:ZrP NPs were determined in MDA-MB-231. The ZrP nanomaterial can be prepared in the 100-200 nm size range with a platelet-like shape. The ZrP NPs themselves are biocompatible, hemocompatible and showed no toxicity to the macrophage cells. ZrP NPs can intercalate high loads (35% w/w) of doxorubicin between their layers. The release of DOX was sustained for about 2 weeks. DOX:ZrP NPs showed higher cellular uptake and increased cytotoxicity than free DOX in MDA-MB-231 cells. ZrP NPs are highly biocompatible, can intercalate large amounts of drugs and sustain the release of drugs. ZrP NPs improved the cellular uptake and cytotoxicity of DOX to MDA-MB-231 cells. ZrP NPs are promising nanocarriers for drug delivery in cancer therapy.The objective of this study was to evaluate the biocompatibility of zirconium phosphate (ZrP) nanoplatelets (NPs), and their use in drug delivery. ZrP and doxorubicin-intercalated ZrP (DOX:ZrP) NPs were characterized by using X-Ray Powder Diffraction (XRPD), Thermogravimetric Analysis (TGA), Transmission Electron Micrography (TEM), Scanning Electron Microscopy (SEM

Imaging of Homeostatic, Neoplastic, and Injured Tissues by HA-Based Probes

Science.gov (United States)

Veiseh, Mandana; Breadner, Daniel; Ma, Jenny; Akentieva, Natalia; Savani, Rashmin C; Harrison, Rene; Mikilus, David; Collis, Lisa; Gustafson, Stefan; Lee, Ting-Yim; Koropatnick, James; Luyt, Leonard G.; Bissell, Mina J.; Turley, Eva A.

2013-01-01

An increase in hyaluronan (HA) synthesis, cellular uptake, and metabolism occurs during the remodeling of tissue microenvironments following injury and during disease processes such as cancer. We hypothesized that multimodality HA-based probes selectively target and detectably accumulate at sites of high HA metabolism, thus providing a flexible imaging strategy for monitoring disease and repair processes. Kinetic analyses confirmed favorable available serum levels of the probe following intravenous (i.v.) or subcutaneous (s.c.) injection. Nuclear (technetium-HA, 99mTc-HA, and iodine-HA, 125I-HA), optical (fluorescent Texas Red-HA, TR-HA), and magnetic resonance (gadolinium-HA, Gd-HA) probes imaged liver (99mTc-HA), breast cancer cells/xenografts (TR-HA, Gd-HA), and vascular injury (125I-HA, TR-HA). Targeting of HA probes to these sites appeared to result from selective HA receptor-dependent localization. Our results suggest that HA-based probes, which do not require polysaccharide backbone modification to achieve favorable half-life and distribution, can detect elevated HA metabolism in homeostatic, injured, and diseased tissues. PMID:22066590

Ultrahigh relaxivity and safe probes of manganese oxide nanoparticles for in vivo imaging.

Science.gov (United States)

Xiao, J; Tian, X M; Yang, C; Liu, P; Luo, N Q; Liang, Y; Li, H B; Chen, D H; Wang, C X; Li, L; Yang, G W

2013-12-05

Mn-based nanoparticles (NPs) have emerged as new class of probes for magnetic resonance imaging due to the impressive contrast ability. However, the reported Mn-based NPs possess low relaxivity and there are no immunotoxicity data regarding Mn-based NPs as contrast agents. Here, we demonstrate the ultrahigh relaxivity of water protons of 8.26 mM(-1) s(-1) from the Mn3O4 NPs synthesized by a simple and green technique, which is twice higher than that of commercial gadolinium (Gd)-based contrast agents (4.11 mM(-1) s(-1)) and the highest value reported to date for Mn-based NPs. We for the first time demonstrate these Mn3O4 NPs biocompatibilities both in vitro and in vivo are satisfactory based on systematical studies of the intrinsic toxicity including cell viability of human nasopharyngeal carcinoma cells, normal nasopharyngeal epithelium, apoptosis in cells and in vivo immunotoxicity. These findings pave the way for the practical clinical diagnosis of Mn based NPs as safe probes for in vivo imaging.

The biocompatibility, integrity, and positional stability of an injectable microstimulator for reanimation of the paralyzed larynx.

Science.gov (United States)

Zealear, D L; Garren, K C; Rodriguez, R J; Reyes, J H; Huang, S; Dokmeci, M R; Najafi, K

2001-08-01

The biocompatibility, integrity, positional stability, and potential use of hermetically sealed injectable wireless micromachined microstimulators were investigated for reanimation of the paralyzed larynx. The device, consisting of silicon and glass, has been tested and proven to be biocompatible with no evidence of pathological tissue reaction or rejection up to one-year implantation in the rat dorsum and canine larynx. By one month, each unit was encapsulated by a thin membrane, which thickened to form a fibrous layer of less than 500 microm at 6-12 months. The microstimulators demonstrated long-term in vivo durability: the hermetic seal of only one in ten devices was breached. Once implanted, migration of the device varied from 0 to 3 cm, depending upon the extent of surgical dissection. No discernable migration was noted when the tissue dissection was minimal. Studies utilizing a modified device equipped with electrodes indicated that migration was nominal with sufficient positional stability to ensure activation of target muscles for glottis opening. This study supported the feasibility of using a microstimulator for reanimation of paralyzed laryngeal muscles that open the airway during breathing. This innovative approach to treatment would alleviate the need for a tracheotomy or surgical resection of the vocal fold.

Controllable synthesis of functional nanocomposites: Covalently functionalize graphene sheets with biocompatible L-lysine

International Nuclear Information System (INIS)

Mo, Zunli; Gou, Hao; He, Jingxian; Yang, Peipei; Feng, Chao; Guo, Ruibin

2012-01-01

Highlights: ► The biocompatible L-lysine functionalized graphene sheets (Gs/Lys) were synthesized controllably using a novel method. ► The Gs/Lys nanocomposites are water-soluble, biocompatible and chiral. ► A chiral graphene derivative was proposed. - Abstract: In this paper a novel method to synthesize functionalize graphene sheets (Gs) by biocompatible L-lysine (Gs/Lys) is reported. The method was composed of two steps: (1) we controllably synthesized self-assembly Gs/Lys-Cu-Lys through the terminal amino of copper L-lysine (Lys-Cu-Lys) attaching to graphite oxide (GO) and then reducing. (2) Obtained the Gs/Lys by eliminating the copper ion. This method could also be used to functionalize other nanomaterials by L-lysine. The Gs/Lys nanocomposites are water-soluble, biocompatible, and above all, it is a chiral material of graphene, which is proposed by us. This novel material will be promising for more applications of graphene. The formation of Gs/Lys nanocomposites were confirmed by scanning electron microscopy (SEM), Fourier-transform infrared spectra (FT-IR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and thermal gravimetric (TG) analysis.

Graphene Films Show Stable Cell Attachment and Biocompatibility with Electrogenic Primary Cardiac Cells

OpenAIRE

Kim, Taeyong; Kahng, Yung Ho; Lee, Takhee; Lee, Kwanghee; Kim, Do Han

2013-01-01

Graphene has attracted substantial attention due to its advantageous materialistic applicability. In the present study, we tested the biocompatibility of graphene films synthesized by chemical vapor deposition with electrogenic primary adult cardiac cells (cardiomyocytes) by measuring the cell properties such as cell attachment, survival, contractility and calcium transients. The results show that the graphene films showed stable cell attachment and excellent biocompatibility with the electro...

Chemical constitution, physical properties, and biocompatibility of experimentally manufactured Portland cement.

Science.gov (United States)

Hwang, Yun-Chan; Kim, Do-Hee; Hwang, In-Nam; Song, Sun-Ju; Park, Yeong-Joon; Koh, Jeong-Tae; Son, Ho-Hyun; Oh, Won-Mann

2011-01-01

An experimental Portland cement was manufactured with pure raw materials under controlled laboratory conditions. The aim of this study was to compare the chemical constitution, physical properties, and biocompatibility of experimentally manufactured Portland cement with those of mineral trioxide aggregate (MTA) and Portland cement. The composition of the cements was determined by scanning electron microscopy (SEM) and energy-dispersive x-ray analysis (EDAX). The setting time and compressive strength were tested. The biocompatibility was evaluated by using SEM and XTT assay. SEM and EDAX revealed the experimental Portland cement to have a similar composition to Portland cement. The setting time of the experimental Portland cement was significantly shorter than that of MTA and Portland cement. The compressive strength of the experimental Portland cement was lower than that of MTA and Portland cement. The experimental Portland cement showed a similar biocompatibility to MTA. The experimental Portland cement might be considered as a possible substitute for MTA in clinical usage after further testing. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

β-cyclodextrin functionalized poly (5-amidoisophthalicacid) grafted Fe{sub 3}O{sub 4} magnetic nanoparticles: A novel biocompatible nanocomposite for targeted docetaxel delivery

Energy Technology Data Exchange (ETDEWEB)

Tarasi, Roghayeh [Department of Chemistry, University of Zanjan, P.O. Box 45195-313, Zanjan (Iran, Islamic Republic of); Khoobi, Mehdi [Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Niknejad, Hassan [Department of Tissue Engineering, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ramazani, Ali [Department of Chemistry, University of Zanjan, P.O. Box 45195-313, Zanjan (Iran, Islamic Republic of); Ma’mani, Leila [Department of Nanotechnology, Agricultural Biotechnology Research Institute of Iran (ABRII), Agricultural Research, Education and Extension Organization (AREEO), Karaj (Iran, Islamic Republic of); Bahadorikhalili, Saeed [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Shafiee, Abbas, E-mail: ashafiee@ams.ac.ir [Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2016-11-01

Thiol-lactam initiated radical polymerization (TLIRP) was successfully employed to prepare poly-N−5-acrylamidoisophthalicacid grafted onto Fe{sub 3}O{sub 4} magnetic nanoparticles (MNPs@PAIP). β-Cyclodextrin (CD) was then conjugated to the carboxylic groups of the prepared MNPs via carbodiimide activation. Subsequently, tumor-targeting folic acid (FA) was attached to the hydroxyl groups of CD on the surface of the latter MNPs to increase the site-specific intracellular delivery. The prepared MNPs were fully characterized by FTIR, VSM, TGA, XRD, FE-SEM and TEM. Docetaxel (DTX) as hydrophobic anticancer drug was loaded via host-guest inclusion complexation with CD and the release profile of the system was studied at different pH. The effect of MNPs on the cell viability was evaluated for the human embryonic kidney normal cell line (HEK293) as well as HeLa and MDA-MB-231 cancerous cell lines and the results did not show any apparent cytotoxic effect. In comparison, DTX loaded MNPs reduced the growth of HeLa and MDA-MB-231 cells more than free DTX. Intracellular uptake ability of DTX loaded MNPs was also studied using fluorescent microscopy and showed cellular uptake about 90% after 4 h treatment. - Highlights: • MNPs@PAIP-CD-FA nanoparticles as a carrier of Doctexal have excellent physical properties. • These nanoparticles are superparamagnetic, biocompatible and non-toxic. • The constructed nanocarrier showed suitable loading capacity and entrapment efficiency.

Improving comparability between microarray probe signals by thermodynamic intensity correction

DEFF Research Database (Denmark)

Bruun, G. M.; Wernersson, Rasmus; Juncker, Agnieszka

2007-01-01

different probes. It is therefore of great interest to correct for the variation between probes. Much of this variation is sequence dependent. We demonstrate that a thermodynamic model for hybridization of either DNA or RNA to a DNA microarray, which takes the sequence-dependent probe affinities...... determination of transcription start sites for a subset of yeast genes. In another application, we identify present/absent calls for probes hybridized to the sequenced Escherichia coli strain O157:H7 EDL933. The model improves the correct calls from 85 to 95% relative to raw intensity measures. The model thus...... makes applications which depend on comparisons between probes aimed at different sections of the same target more reliable....

Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

Directory of Open Access Journals (Sweden)

Panoraia I. Siafaka

2016-08-01

Full Text Available Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic–organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the “state of the art” of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined.

Probing nuclear structure with nucleons

International Nuclear Information System (INIS)

Bauge, E.

2007-01-01

The goal of this lecture is to show how nucleon scattering can be used to probe the structure of target nuclei, and how nucleon scattering observables can be interpreted in terms of nuclear structure using microscopic optical potentials. After a brief overview of the specificities of nucleon-nucleus scattering, and a quick reminder on scattering theory, the main part of this lecture is devoted to the construction of optical potentials in which the target nuclei structure information is folded with an effective interaction. Several examples of such microscopic optical model potentials are given. (author)

G-stack modulated probe intensities on expression arrays - sequence corrections and signal calibration

Directory of Open Access Journals (Sweden)

Fasold Mario

2010-04-01

Full Text Available Abstract Background The brightness of the probe spots on expression microarrays intends to measure the abundance of specific mRNA targets. Probes with runs of at least three guanines (G in their sequence show abnormal high intensities which reflect rather probe effects than target concentrations. This G-bias requires correction prior to downstream expression analysis. Results Longer runs of three or more consecutive G along the probe sequence and in particular triple degenerated G at its solution end ((GGG1-effect are associated with exceptionally large probe intensities on GeneChip expression arrays. This intensity bias is related to non-specific hybridization and affects both perfect match and mismatch probes. The (GGG1-effect tends to increase gradually for microarrays of later GeneChip generations. It was found for DNA/RNA as well as for DNA/DNA probe/target-hybridization chemistries. Amplification of sample RNA using T7-primers is associated with strong positive amplitudes of the G-bias whereas alternative amplification protocols using random primers give rise to much smaller and partly even negative amplitudes. We applied positional dependent sensitivity models to analyze the specifics of probe intensities in the context of all possible short sequence motifs of one to four adjacent nucleotides along the 25meric probe sequence. Most of the longer motifs are adequately described using a nearest-neighbor (NN model. In contrast, runs of degenerated guanines require explicit consideration of next nearest neighbors (GGG terms. Preprocessing methods such as vsn, RMA, dChip, MAS5 and gcRMA only insufficiently remove the G-bias from data. Conclusions Positional and motif dependent sensitivity models accounts for sequence effects of oligonucleotide probe intensities. We propose a positional dependent NN+GGG hybrid model to correct the intensity bias associated with probes containing poly-G motifs. It is implemented as a single-chip based calibration

Chemical Probes of Histone Lysine Methyltransferases

Science.gov (United States)

2015-01-01

Growing evidence suggests that histone methyltransferases (HMTs, also known as protein methyltransferases (PMTs)) play an important role in diverse biological processes and human diseases by regulating gene expression and the chromatin state. Therefore, HMTs have been increasingly recognized by the biomedical community as a class of potential therapeutic targets. High quality chemical probes of HMTs, as tools for deciphering their physiological functions and roles in human diseases and testing therapeutic hypotheses, are critical for advancing this promising field. In this review, we focus on the discovery, characterization, and biological applications of chemical probes for HMTs. PMID:25423077

Chemical proteomics approach reveals the direct targets and the heme-dependent activation mechanism of artemisinin in Plasmodium falciparum using an activity-based artemisinin probe

Directory of Open Access Journals (Sweden)

Jigang Wang

2016-04-01

Full Text Available Artemisinin and its analogues are currently the most effective anti-malarial drugs. The activation of artemisinin requires the cleavage of the endoperoxide bridge in the presence of iron sources. Once activated, artemisinins attack macromolecules through alkylation and propagate a series of damages, leading to parasite death. Even though several parasite proteins have been reported as artemisinin targets, the exact mechanism of action (MOA of artemisinin is still controversial and its high potency and specificity against the malaria parasite could not be fully accounted for. Recently, we have developed an unbiased chemical proteomics approach to directly probe the MOA of artemisinin in P. falciparum. We synthesized an activity-based artemisinin probe with an alkyne tag, which can be coupled with biotin through click chemistry. This enabled selective purification and identification of 124 protein targets of artemisinin. Many of these targets are critical for the parasite survival. In vitro assays confirmed the specific artemisinin binding and inhibition of selected targets. We thus postulated that artemisinin kills the parasite through disrupting its biochemical landscape. In addition, we showed that artemisinin activation requires heme, rather than free ferrous iron, by monitoring the extent of protein binding using a fluorescent dye coupled with the alkyne-tagged artemisinin. The extremely high level of heme released from the hemoglobin digestion by the parasite makes artemisinin exceptionally potent against late-stage parasites (trophozoite and schizont stages compared to parasites at early ring stage, which have low level of heme, possibly derived from endogenous synthesis. Such a unique activation mechanism also confers artemisinin with extremely high specificity against the parasites, while the healthy red blood cells are unaffected. Our results provide a sound explanation of the MOA of artemisinin and its specificity against malaria

BIOCOMPATIBLE FLUORESCENT MICROSPHERES: SAFE PARTICLES FOR MATERIAL PENETRATION STUDIES

Energy Technology Data Exchange (ETDEWEB)

Farquar, G; Leif, R

2009-07-15

Biocompatible polymers with hydrolyzable chemical bonds have been used to produce safe, non-toxic fluorescent microspheres for material penetration studies. The selection of polymeric materials depends on both biocompatibility and processability, with tailored fluorescent properties depending on specific applications. Microspheres are composed of USFDA-approved biodegradable polymers and non-toxic fluorophores and are therefore suitable for tests where human exposure is possible. Micropheres were produced which contain unique fluorophores to enable discrimination from background aerosol particles. Characteristics that affect dispersion and adhesion can be modified depending on use. Several different microsphere preparation methods are possible, including the use of a vibrating orifice aerosol generator (VOAG), a Sono-Tek atomizer, an emulsion technique, and inkjet printhead. Applications for the fluorescent microspheres include challenges for biodefense system testing, calibrants for biofluorescence sensors, and particles for air dispersion model validation studies.

Synthesis and toxicity test of magnetic nanoparticle via biocompatible microemulsion system as template for application in targeted drug delivery

Science.gov (United States)

Kader, Razinah Abdul; Rose, Laili Che; Suhaimi, Hamdan; Manickam, Mariessa Soosai

2017-09-01

This work reports the preparation of magnetic nanoparticles (FeNPs) using biocompatible W/O microemulsion for biomedical applications. W/O microemulsion was formed using decane as oil phase, water, tween 80 as non-ionic surfactant and hexanol as organic solvent. The synthesized FeNPs were characterised by using Fourier Transform Infrared Resonance Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and X-Ray Diffraction (XRD). The FTIR showed that Fe-O bond exist on 581cm-1 having strong magnetic strength whereas SEM showed the morphology surface of magnetic nanoparticles (FeNPs). Furthermore, analysis of XRD pattern magnetic nanoparticles (FeNPs) reveals a cubic iron oxide phase with good crystallize structure. Furthermore, toxicity test on human liver cells proved that it is 70% safe on human and proved to be a safety nanomedicine.

Development and applications of advanced probing tools for cell wall biology

DEFF Research Database (Denmark)

Hansen, Aleksander Riise

. In this study, antigens consisting of crude mixtures of alkali extracted polymers from the grass model Brachypodium distachyon were targets for probe generation using a naïve human single domain antibody library. Epitope characterization of positive clones from phage ELISA was then further elucidated...... the function of pectin methyl esterase inhibitors and their role in plant defense against microbial degradation, and cell wall structural dynamics in relation to cell detachment from roots. The second part describes phage display as a method for developing probes against targets that are poor immunogens...

An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

OpenAIRE

Nuss, Katja MR; Auer, Joerg A; Boos, Alois; Rechenberg, Brigitte von

2006-01-01

Abstract Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Result...

Antimicrobial and biocompatible properties of nanomaterials.

Science.gov (United States)

Ul-Islam, M; Shehzad, A; Khan, S; Khattak, W A; Ullah, M W; Park, J K

2014-01-01

The rapid development of drug-resistant characteristics in pathogenic viral, bacterial, and fungal species and the consequent spread of infectious diseases are currently receiving serious attention. Indeed, there is a pressing demand to explore novel materials and develop new strategies that can address these issues of serious concern. Nanomaterials are currently proving to be the most capable therapeutic agents to cope with such hazards. The exceptional physiochemical properties and impressive antimicrobial capabilities of nanoparticles have provoked their utilization in biomedical fields. Nanomaterials of both organic and inorganic nature have shown the capabilities of disrupting microbial cells through different mechanisms. Along with the direct influence on the microbial cell membrane, DNA and proteins, these nanomaterials produce reactive oxygen species (ROS) that damage cell components and viruses. Currently, a serious hazard associated with these antimicrobial nanomaterials is their toxicity to human and animal cells. Extensive studies have reported the dose, time, and cell-dependent toxicology of various nanomaterials, and some have shown excellent biocompatible properties. Nevertheless, there is still debate regarding the use of nanomaterials for medical applications. Therefore, in this review, the antimicrobial activities of various nanomaterials with details of their acting mechanisms were compiled. The relative toxic and biocompatible behavior of nanomaterials emphasized in this study provides information pertaining to their practical applicability in medical fields.

Biocompatibility of Soft-Templated Mesoporous Carbons

Energy Technology Data Exchange (ETDEWEB)

Gencoglu, Maria F. [Michigan Technological Univ., Houghton, MI (United States). Dept. of Chemical Engineering; Spurri, Amanda [Widener Univ., Chester, PA (United States). Dept. of Chemical Engineering; Franko, Mitchell [Widener Univ., Chester, PA (United States). Dept. of Chemical Engineering; Chen, Jihua [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Science (CNMS); Hensley, Dale K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Center for Nanophase Materials Science (CNMS); Heldt, Caryn L. [Michigan Technological Univ., Houghton, MI (United States). Dept. of Chemical Engineering; Saha, Dipendu [Widener Univ., Chester, PA (United States). Dept. of Chemical Engineering

2014-08-21

We report that soft-templated mesoporous carbon is morphologically a non-nano type of carbon. It is a relatively newer variety of biomaterial, which has already demonstrated its successful role in drug delivery applications. To investigate the toxicity and biocompatibility, we introduced three types of mesoporous carbons with varying synthesis conditions and pore textural properties. We compared the Brunauer–Emmett–Teller (BET) surface area and pore width and performed cytotoxicity experiments with HeLa cells, cell viability studies with fibroblast cells and hemocomapatibility studies. Cytotoxicity tests reveal that two of the carbons are not cytotoxic, with cell survival over 90%. The mesoporous carbon with the highest surface area showed slight toxicity (~70% cell survival) at the highest carbon concentration of 500 μg/mL. Fibroblast cell viability assays suggested high and constant viability of over 98% after 3 days with no apparent relation with materials property and good visible cell-carbon compatibility. No hemolysis (<1%) was confirmed for all the carbon materials. Protein adsorption experiments with bovine serum albumin (BSA) and fibrinogen revealed a lower protein binding capacity of 0.2–0.6 mg/m² and 2–4 mg/m² for BSA and fibrinogen, respectively, with lower binding associated with an increase in surface area. The results of this study confirm the biocompatibility of soft-templated mesoporous carbons.

Biocompatibility and characterisation of a candidate microelectrode material for biosensor applications

International Nuclear Information System (INIS)

Cyster, L.A.

2001-10-01

Recent advances in microcircuit technology have enabled the fabrication of Multiple Microelectrode Arrays (MEAs) for investigating the characteristics of networks of neuronal cells either in vivo or in vitro. When producing a MEA materials used must be corrosion resistant, have low electrical impedance and the materials must be biocompatible. Existing MEA's have limited life spans, relatively high impedance values and limited uses. Thus creating a requirement for new MEA technology. TiN thin films have become increasingly useful in a wide variety of applications, due to their nature, which includes chemical stability, high hardness, excellent wear and electrical properties and also biocompatibility. The favourable electrical and biocompatibility characteristics of thin films of TiN make them a possible candidate for use in a MEA. TiN thin films can be deposited by a number of methods including evaporation, ion plating and sputtering. The method of deposition, along with process parameters used can have a marked effect on the characteristics of TiN films, including changes in preferred orientation, hardness and wear and also biocompatibility. TiN thin films were deposited onto glass substrates by pulsed DC reactive sputtering of a Ti target, with Argon and nitrogen gas mixtures and labelled Type I TiN films. Also industrial TIN films deposited by Arc Ion plating were carefully selected for comparison and labelled Type II TiN films. The microstructure, composition, surface chemistry, surface topography and roughness were studied using X-Ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Atomic Force Microscopy (AFM) and Profilometry. Type I TIN films showed a surface topography similar to Zone I and Type II TiN films showed a surface topography similar to Zone 2 of the Movchan and Dernchishin structure zone model for sputtered films. XPS showed that the surface composition of all TiN films was predominantly TiO 2 , TiN and TiN x O y . Significant

Modified titanium surface with gelatin nano gold composite increases osteoblast cell biocompatibility

International Nuclear Information System (INIS)

Lee, Young-Hee; Bhattarai, Govinda; Aryal, Santosh; Lee, Nan-Hee; Lee, Min-Ho; Kim, Tae-Gun; Jhee, Eun-Chung; Kim, Hak-Yong; Yi, Ho-Keun

2010-01-01

This study examined the gelatin nano gold (GnG) composite for surface modification of titanium in addition to insure biocompatibility on dental implants or biomaterials. The GnG composite was constructed by gelatin and hydrogen tetrachloroaurate in presence of reducing agent, sodium borohydrate (NabH 4 ). The GnG composite was confirmed by UV-VIS spectroscopy and transmission electron microscopy (TEM). A dipping method was used to modify the titanium surface by GnG composite. Surface was characterized by scanning electron microscopy (SEM) and energy dispersive X-ray (EDX). The MC-3T3 E1 cell viability was assessed by trypan blue and the expression of proteins to biocompatibility were analyzed by Western blotting. The GnG composite showed well dispersed character, the strong absorption at 530 nm, roughness, regular crystal and clear C, Na, Cl, P, and Au signals onto titanium. Further, this composite allowed MC-3T3 E1 growth and viability compared to gelatin and pure titanium. It induced ERK activation and the expression of cell adherent molecules, FAK and SPARC, and growth factor, VEGF. However, GnG decreased the level of SAPK/JNK. This shows that GnG composite coated titanium surfaces have a good biocompatibility for osteoblast growth and attachment than in intact by simple and versatile dipping method. Furthermore, it offers good communication between cell and implant surfaces by regulating cell signaling and adherent molecules, which are useful to enhance the biocompatibility of titanium surfaces.

In vivo qualitative analysis of the biocompatibility of different cyanoacrylate-based adhesives

Directory of Open Access Journals (Sweden)

Rafael Tobias Moretti Neto

2008-03-01

Full Text Available Cyanocrylates have been widely used in the medical and dental fields for several years. In Dentistry, cyanoacrylates have been used for suturing, pulp capping, as retrofilling material in endodontic surgeries, and as cervical plug for pulpless teeth bleaching. The biocompatibility of these adhesives has been the topic of many researches and subcutaneous implantation is an effective methodology for these studies. The present study evaluated the biocompatibility of three different cyanoacrylate-based adhesives. Thirty-six Wistar rats were used, divided into four groups of 9 animals each: A (control - distilled water, B - cyanoacrylate ester (Super Bonder, C - n-butyl-cyanoacrylate (Histoacryl and D - alpha-cyanoacrylate (Three Bond. The materials were dispensed in sponges of polyvinyl chloride, the animals were incised and the sponges were inserted in the subcutaneous tissue and sutured. Each group was sub-divided according to the time of sacrifice of the animals: 7, 21 and 45 days. Subjective analysis of the histologic material showed that all groups presented some degree of irritability, but the inflammatory reaction decreased with the experimental time in all groups. Group D showed an inflammatory reaction which was closer to that of the control group and was considered to have good biocompatibility. Groups B and C were similar and presented more aggressive inflammatory reactions when compared to the control group. Based on the results, it was concluded that alpha-cyanoacrylate (Three Bond was the most biocompatible adhesive because it caused the lowest levels of inflammation.

Structural Probing of Off-Target G Protein-Coupled Receptor Activities within a Series of Adenosine/Adenine Congeners

Science.gov (United States)

Paoletta, Silvia; Tosh, Dilip K.; Salvemini, Daniela; Jacobson, Kenneth A.

2014-01-01

We studied patterns of off-target receptor interactions, mostly at G protein-coupled receptors (GPCRs) in the µM range, of nucleoside derivatives that are highly engineered for nM interaction with adenosine receptors (ARs). Because of the considerable interest of using AR ligands for treating diseases of the CNS, we used the Psychoactive Drug Screening Program (PDSP) for probing promiscuity of these adenosine/adenine congeners at 41 diverse receptors, channels and a transporter. The step-wise truncation of rigidified, trisubstituted (at N6, C2, and 5′ positions) nucleosides revealed unanticipated interactions mainly with biogenic amine receptors, such as adrenergic receptors and serotonergic receptors, with affinities as high as 61 nM. The unmasking of consistent sets of structure activity relationship (SAR) at novel sites suggested similarities between receptor families in molecular recognition. Extensive molecular modeling of the GPCRs affected suggested binding modes of the ligands that supported the patterns of SAR at individual receptors. In some cases, the ligand docking mode closely resembled AR binding and in other cases the ligand assumed different orientations. The recognition patterns for different GPCRs were clustered according to which substituent groups were tolerated and explained in light of the complementarity with the receptor binding site. Thus, some likely off-target interactions, a concern for secondary drug effects, can be predicted for analogues of this set of substructures, aiding the design of additional structural analogues that either eliminate or accentuate certain off-target activities. Moreover, similar analyses could be performed for unrelated structural families for other GPCRs. PMID:24859150

The biocompatibility of fluorescent nanodiamonds and their mechanism of cellular uptake

International Nuclear Information System (INIS)

Vaijayanthimala, Vairakkannu; Tzeng, Yan-Kai; Chang, Huan-Cheng; Li, Chung-Leung

2009-01-01

The labeling of cells with fluorescent nanoparticles is promising for various biomedical applications. The objective of this study is to evaluate the biocompatibility and the mechanism of the cellular uptake of fluorescent nanodiamonds (FNDs) in cancer cells (HeLa) and pre-adipocytes (3T3-L1). With flow cytometry and the use of a battery of metabolic and cytoskeletal inhibitors, we found that the mechanism of the FND uptake in both cells is by energy-dependent clathrin-mediated endocytosis. In addition, the surface charge of FND influences its cellular uptake, as the uptake of poly-L-lysine-coated FNDs is better than that of oxidative-acid-purified FNDs at the same concentration in regular medium with or without serum. We also confirm that the proliferative potential of FND-treated and untreated cells does not exhibit any significant differences when measured at bulk cultures, and more stringently at clonal cell density. Further biocompatibility studies indicate that the in vitro differentiation of 3T3-L1 pre-adipocytes and 489-2 osteoprogenitors is not affected by the FND treatment. Our results show that FNDs are biocompatible and ideal candidates for potential applications in human stem cell research.

The biocompatibility of fluorescent nanodiamonds and their mechanism of cellular uptake

Energy Technology Data Exchange (ETDEWEB)

Vaijayanthimala, Vairakkannu; Tzeng, Yan-Kai; Chang, Huan-Cheng [Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan (China); Li, Chung-Leung, E-mail: hcchang@po.sinica.edu.t, E-mail: chungL@gate.sinica.edu.t [Genomics Research Center, Academia Sinica, Taipei 115, Taiwan (China)

2009-10-21

The labeling of cells with fluorescent nanoparticles is promising for various biomedical applications. The objective of this study is to evaluate the biocompatibility and the mechanism of the cellular uptake of fluorescent nanodiamonds (FNDs) in cancer cells (HeLa) and pre-adipocytes (3T3-L1). With flow cytometry and the use of a battery of metabolic and cytoskeletal inhibitors, we found that the mechanism of the FND uptake in both cells is by energy-dependent clathrin-mediated endocytosis. In addition, the surface charge of FND influences its cellular uptake, as the uptake of poly-L-lysine-coated FNDs is better than that of oxidative-acid-purified FNDs at the same concentration in regular medium with or without serum. We also confirm that the proliferative potential of FND-treated and untreated cells does not exhibit any significant differences when measured at bulk cultures, and more stringently at clonal cell density. Further biocompatibility studies indicate that the in vitro differentiation of 3T3-L1 pre-adipocytes and 489-2 osteoprogenitors is not affected by the FND treatment. Our results show that FNDs are biocompatible and ideal candidates for potential applications in human stem cell research.

Flexible organic light emitting diodes fabricated on biocompatible silk fibroin substrate

International Nuclear Information System (INIS)

Liu, Yuqiang; Xie, Yuemin; Liu, Yuan; Song, Tao; Liao, Liangsheng; Sun, Baoquan; Zhang, Ke-Qin

2015-01-01

Flexible and biodegradable electronics are currently under extensive investigation for biocompatible and environmentally-friendly applications. Synthetic plastic foils are widely used as substrates for flexible electronics. But typical plastic substrates such as polyethylene naphthalate (PEN) could not be degraded in a natural bio-environment. A great demand still exists for a next-generation biocompatible and biodegradable substrate for future application. For example, electronic devices can be potentially integrated into the human body. In this work, we demonstrate that the biocompatible and biodegradable natural silk fibroin (SF) films embedded with silver nanowires (AgNWs) mesh could be employed as conductive transparent substrates to fabricate flexible organic light emitting diodes (OLEDs). Compared with commercial PEN substrates coated with indium tin oxide, the AgNWs/SF composite substrates exhibit a similar sheet resistance of 12 Ω sq −1 , a lower surface roughness, as well as a broader light transmission range. Flexible OLEDs based on AgNWs/SF substrates achieve a current efficiency of 19 cd A −1 , demonstrating the potential of the flexible AgNWs/SF films as conductive and transparent substrates for next-generation biodegradable devices. (paper)

Flexible organic light emitting diodes fabricated on biocompatible silk fibroin substrate

Science.gov (United States)

Liu, Yuqiang; Xie, Yuemin; Liu, Yuan; Song, Tao; Zhang, Ke-Qin; Liao, Liangsheng; Sun, Baoquan

2015-10-01

Flexible and biodegradable electronics are currently under extensive investigation for biocompatible and environmentally-friendly applications. Synthetic plastic foils are widely used as substrates for flexible electronics. But typical plastic substrates such as polyethylene naphthalate (PEN) could not be degraded in a natural bio-environment. A great demand still exists for a next-generation biocompatible and biodegradable substrate for future application. For example, electronic devices can be potentially integrated into the human body. In this work, we demonstrate that the biocompatible and biodegradable natural silk fibroin (SF) films embedded with silver nanowires (AgNWs) mesh could be employed as conductive transparent substrates to fabricate flexible organic light emitting diodes (OLEDs). Compared with commercial PEN substrates coated with indium tin oxide, the AgNWs/SF composite substrates exhibit a similar sheet resistance of 12 Ω sq-1, a lower surface roughness, as well as a broader light transmission range. Flexible OLEDs based on AgNWs/SF substrates achieve a current efficiency of 19 cd A-1, demonstrating the potential of the flexible AgNWs/SF films as conductive and transparent substrates for next-generation biodegradable devices.

Carbon foam/hydroxyapatite coating for carbon/carbon composites: Microstructure and biocompatibility

Energy Technology Data Exchange (ETDEWEB)

Zhang, Leilei, E-mail: zhangleilei1121@aliyun.com; Li, Hejun; Li, Kezhi; Zhang, Shouyang; Lu, Jinhua; Li, Wei; Cao, Sheng; Wang, Bin

2013-12-01

To improve the surface biocompatibility of carbon/carbon composites, a carbon foam/hydroxyapatite coating was applied using a combination method of slurry procedure and ultrasound-assisted electrochemical deposition procedure. The morphology, microstructure and chemical composition of the coating were investigated by scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy and X-ray diffraction. The biocompatibility of the carbon foam/hydroxyapatite coating was investigated by osteoblast-like MG63 cell culture tests. The results showed that the carbon foam could provide a large number of pores on the surface of carbon/carbon composites. The hydroxyapatite crystals could infiltrate into the pores and form the carbon foam/hydroxyapatite coating. The coating covered the carbon/carbon composites fully and uniformly with slice morphology. The cell response tests showed that the MG63 cells on carbon foam/hydroxyapatite coating had a better cell adhesion and cell proliferation than those on uncoated carbon/carbon composites. The carbon foam/hydroxyapatite coatings were cytocompatible and were beneficial to improve the biocompatibility. The approach presented here may be exploited for fabrication of carbon/carbon composite implant surfaces.

Carbon foam/hydroxyapatite coating for carbon/carbon composites: Microstructure and biocompatibility

International Nuclear Information System (INIS)

Zhang, Leilei; Li, Hejun; Li, Kezhi; Zhang, Shouyang; Lu, Jinhua; Li, Wei; Cao, Sheng; Wang, Bin

2013-01-01

To improve the surface biocompatibility of carbon/carbon composites, a carbon foam/hydroxyapatite coating was applied using a combination method of slurry procedure and ultrasound-assisted electrochemical deposition procedure. The morphology, microstructure and chemical composition of the coating were investigated by scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy and X-ray diffraction. The biocompatibility of the carbon foam/hydroxyapatite coating was investigated by osteoblast-like MG63 cell culture tests. The results showed that the carbon foam could provide a large number of pores on the surface of carbon/carbon composites. The hydroxyapatite crystals could infiltrate into the pores and form the carbon foam/hydroxyapatite coating. The coating covered the carbon/carbon composites fully and uniformly with slice morphology. The cell response tests showed that the MG63 cells on carbon foam/hydroxyapatite coating had a better cell adhesion and cell proliferation than those on uncoated carbon/carbon composites. The carbon foam/hydroxyapatite coatings were cytocompatible and were beneficial to improve the biocompatibility. The approach presented here may be exploited for fabrication of carbon/carbon composite implant surfaces.

Polyaniline cryogels: Biocompatibility of novel conducting macroporous material

Czech Academy of Sciences Publication Activity Database

Humpolíček, P.; Radaszkiewicz, K. A.; Capáková, Z.; Pacherník, J.; Bober, Patrycja; Kašpárková, V.; Rejmontová, P.; Lehocký, M.; Ponížil, P.; Stejskal, Jaroslav

2018-01-01

Roč. 8, 09 January (2018), s. 1-12, č. článku 135. ISSN 2045-2322 R&D Projects: GA ČR(CZ) GA17-05095S Institutional support: RVO:61389013 Keywords : polyaniline * cryogel * biocompatibility Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 4.259, year: 2016

Biodegradability and Biocompatibility Study of Poly(Chitosan-g-lactic Acid Scaffolds

Directory of Open Access Journals (Sweden)

Zhe Zhang

2012-03-01

Full Text Available A biodegradable, biocompatible poly(chitosan-g-lactic acid (PCLA scaffold was prepared and evaluated in vitro and in vivo. The PCLA scaffold was obtained by grafting lactic acid (LA onto the amino groups on chitosan (CS without a catalyst. The PCLA scaffolds were characterized by Fourier Transform infrared spectroscopy (FT-IR and scanning electron microscopy (SEM. The biodegradabilty was determined by mass loss in vitro, and degradation in vivo as a function of feed ratio of LA/CS. Bone marrow mesenchymal stem cell (BMSC culture experiments and histological examination were performed to evaluate the PCLA scaffolds’ biocompatibility. The results indicated that PCLA was promising for tissue engineering application.

Intra-Tissue Pressure Measurement in Ex Vivo Liver Undergoing Laser Ablation with Fiber-Optic Fabry-Perot Probe

Directory of Open Access Journals (Sweden)

Daniele Tosi

2016-04-01

Full Text Available We report the first-ever intra-tissue pressure measurement performed during 1064 nm laser ablation (LA of an ex vivo porcine liver. Pressure detection has been performed with a biocompatible, all-glass, temperature-insensitive Extrinsic Fabry-Perot Interferometry (EFPI miniature probe; the proposed methodology mimics in-vivo treatment. Four experiments have been performed, positioning the probe at different positions from the laser applicator tip (from 0.5 mm to 5 mm. Pressure levels increase during ablation time, and decrease with distance from applicator tip: the recorded peak parenchymal pressure levels range from 1.9 kPa to 71.6 kPa. Different pressure evolutions have been recorded, as pressure rises earlier in proximity of the tip. The present study is the first investigation of parenchymal pressure detection in liver undergoing LA: the successful detection of intra-tissue pressure may be a key asset for improving LA, as pressure levels have been correlated to scattered recurrences of tumors by different studies.

Click chemistry on the surface of PLGA-b-PEG polymeric nanoparticles: a novel targetable fluorescent imaging nanocarrier

Energy Technology Data Exchange (ETDEWEB)

Pucci, Andrea; Locatelli, Erica [University of Bologna, Dipartimento di Chimica Industriale ' Toso Montanari' (Italy); Ponti, Jessica; Uboldi, Chiara [Institute for Health and Consumer Protection, Joint Research Centre, Nanobiosciences Unit (Italy); Molinari, Valerio; Comes Franchini, Mauro, E-mail: mauro.comesfranchini@unibo.it [University of Bologna, Dipartimento di Chimica Industriale ' Toso Montanari' (Italy)

2013-08-15

In the quest for biocompatible nanocarriers for biomedical applications, a great deal of effort is put on engineering the nanocomposites surface in order to render them specific to the particular purpose. We developed biocompatible PLGA-b-PEG-based nanoparticles carrying a double functionality (i.e., carboxylic and acetylenic) able to serve as flexible highly selective grafting centers for cancer diagnosis and treatment. As a proof of concept, the nanocarrier was successfully functionalized with a tailored fluorescent molecule by means of click chemistry and with a targeting agent specific for glioblastoma multiforme via amidic bond formation.

Biocompatibility of biomaterials - Lessons learned and considerations for the design of novel materials.

Science.gov (United States)

Schmalz, Gottfried; Galler, Kerstin M

2017-04-01

Biocompatibility of dental materials has gained increasing interest during recent decades. Meanwhile, legal regulations and standard test procedures are available to evaluate biocompatibility. Herein, these developments will be exemplarily outlined and some considerations for the development of novel materials will be provided. Different aspects including test selection, release of substances, barriers, tissue healing, antibacterial substances, nanoparticles and environmental aspects will be covered. The provided information is mainly based on a review of the relevant literature in international peer reviewed journals, on regulatory documents and on ISO standards. Today, a structured and systematic approach for demonstrating biocompatibility from both a scientific and regulatory point of view is based on a clinical risk assessment in an early stage of material development. This includes the analysis of eluted substances and relevant barriers like dentin or epithelium. ISO standards 14971, 10993, and 7405 specify the modes for clinical risk assessment, test selection and test performance. In contact with breached tissues, materials must not impair the healing process. Antibacterial effects should be based on timely controllable substances or on repellant surfaces. Nanoparticles are produced by intraoral grinding irrespective of the content of nanoparticles in the material, but apparently at low concentrations. Concerns regarding environmental aspects of mercury from amalgam can be met by amalgam separating devices. The status for other materials (e.g. bisphenol-A in resin composites) needs to be evaluated. Finally, the public interest for biocompatibility issues calls for a suitable strategy of risk communication. A wise use of the new tools, especially the clinical risk assessment should aim at preventing the patients, professionals and the environment from harm but should not block the development of novel materials. However, biocompatibility must always be

Biofabrication of a novel biomolecule-assisted reduced graphene oxide: an excellent biocompatible nanomaterial

Directory of Open Access Journals (Sweden)

Zhang X

2016-12-01

Full Text Available Xi-Feng Zhang,1 Sangiliyandi Gurunathan2 1College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, People’s Republic of China; 2Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, Republic of Korea Abstract: Graphene has been shown much interest, both in academics and industry due to its extraordinary physical, chemical, and biological proprieties. It shows great promises in biotechnological and biomedical applications as an antibacterial and anticancer agent, nanocarrier, sensor, etc. However, many studies demonstrated the toxicity of graphene in several cell lines, which is an obstacle to its use in biomedical applications. In this study, to improve the biocompatibility of graphene, we used nicotinamide (NAM as a reducing and stabilizing agent to catalyze the reduction of graphene oxide (GO to reduced graphene oxide (rGO. The resulted smaller-sized GO (NAM-rGO showed excellent biocompatibility with mouse embryonic fibroblast cells, evidenced by various cellular assays. Furthermore, NAM-rGO had no effect on mitochondrial membrane permeability and caspase-3 activity compared to GO. Reverse transcription polymerase chain reaction analysis allowed us to identify the molecular mechanisms responsible for NAM-rGO-induced biocompatibility. NAM-rGO significantly induced the expression of genes encoding tight junction proteins (TJPs such as zona occludens-1 (Tjp1 and claudins (Cldn3 without any effect on the expression of cytoskeleton proteins. Furthermore, NAM-rGO enhances the expression of alkaline phosphatase (ALP gene, and it does this in a time-dependent manner. Overall, our study depicted the molecular mechanisms underlying NAM-rGO biocompatibility depending on upregulation of TJPs and ALP. This potential quality of graphene could be used in diverse applications including tissue regeneration and tissue engineering. Keywords: biocompatibility, graphene oxide, nicotinamide, reduced

Gene probes : principles and protocols [Methods in molecular biology, v. 179

National Research Council Canada - National Science Library

Rapley, Ralph; Aquino de Muro, Marilena

2002-01-01

... of labeled DNA has allowed genes to be mapped to single chromosomes and in many cases to a single chromosome band, promoting significant advance in human genome mapping. Gene Probes: Principles and Protocols presents the principles for gene probe design, labeling, detection, target format, and hybridization conditions together with detailed protocols, accom...

Design Concept of Dialyzer Biomaterials: How to Find Biocompatible Polymers Based on the Biointerfacial Water Structure.

Science.gov (United States)

Tanaka, Masaru

2017-01-01

Although various types of materials have been used widely in dialyzers, most biomaterials lack the desired functional properties to interface with blood and have not been engineered for optimum performance. Therefore, there is increasing demand to develop novel materials to address such problems in the dialysis arena. Numerous parameters of polymeric biomaterials can affect biocompatibility in a controlled manner. The mechanisms responsible for the biocompatibility of polymers at the molecular level have not been clearly demonstrated, although many theoretical and experimental efforts have been made to try and understand them. Moreover, water interactions have been recognized as fundamental for the blood response to contact with polymers. We have proposed the 'intermediate water' concept and hypothesized that intermediate water, which prevents the proteins and blood cells from directly contacting the polymer surface, or nonfreezing water on the polymer surface, plays an important role in the biocompatibility of polymers. This chapter provides an overview of the recent experimental progress of biocompatible polymers measured by thermal, spectroscopic, and surface force techniques. Additionally, it highlights recent developments in the use of biocompatible polymeric biomaterials for dialyzers and provides an overview of the progress made in the design of multifunctional biomedical polymers by controlling the biointerfacial water structure through precision polymer synthesis. Key Messages: Intermediate water was found only in hydrated biopolymers (proteins, polysaccharides, and nucleic acids, DNA and RNA) and hydrated biocompatible synthetic polymers. Intermediate water could be one of the main screening factors for the design of appropriate dialyzer materials. © 2017 S. Karger AG, Basel.

Development of a Biocompatible Layer-by-Layer Film System Using Aptamer Technology for Smart Material Applications

Directory of Open Access Journals (Sweden)

Amanda Foster

2014-05-01

Full Text Available Aptamers are short, single-stranded nucleic acids that fold into well-defined three dimensional (3D structures that allow for binding to a target molecule with affinities and specificities that can rival or in some cases exceed those of antibodies. The compatibility of aptamers with nanostructures such as thin films, in combination with their affinity, selectivity, and conformational changes upon target interaction, could set the foundation for the development of novel smart materials. In this study, the development of a biocompatible aptamer-polyelectrolyte film system was investigated using a layer-by-layer approach. Using fluorescence microscopy, we demonstrated the ability of the sulforhodamine B aptamer to bind its cognate target while sequestered in a chitosan-hyaluronan film matrix. Studies using Ultraviolet-visible (UV-Vis spectrophotometry also suggest that deposition conditions such as rinsing time and volume play a strong role in the internal film interactions and growth mechanisms of chitosan-hyaluronan films. The continued study and development of aptamer-functionalized thin films provides endless new opportunities for novel smart materials and has the potential to revolutionize the field of controlled release.

Heating ability and biocompatibility study of silica-coated magnetic ...

Indian Academy of Sciences (India)

Home; Journals; Bulletin of Materials Science; Volume 38; Issue 6. Heating ability and biocompatibility study of silica-coated magnetic nanoparticles as heating mediators for magnetic hyperthermia and magnetically triggered drug delivery systems. Meysam Soleymani Mohammad Edrissi. Volume 38 Issue 6 October 2015 ...

Intrinsically Labeled Fluorescent Oligonucleotide Probes on Quantum Dots for Transduction of Nucleic Acid Hybridization.

Science.gov (United States)

Shahmuradyan, Anna; Krull, Ulrich J

2016-03-15

Quantum dots (QDs) have been widely used in chemical and biosensing due to their unique photoelectrical properties and are well suited as donors in fluorescence resonance energy transfer (FRET). Selective hybridization interactions of oligonucleotides on QDs have been determined by FRET. Typically, the QD-FRET constructs have made use of labeled targets or have implemented labeled sandwich format assays to introduce dyes in proximity to the QDs for the FRET process. The intention of this new work is to explore a method to incorporate the acceptor dye into the probe molecule. Thiazole orange (TO) derivatives are fluorescent intercalating dyes that have been used for detection of double-stranded nucleic acids. One such dye system has been reported in which single-stranded oligonucleotide probes were doubly labeled with adjacent thiazole orange derivatives. In the absence of the fully complementary (FC) oligonucleotide target, the dyes form an H-aggregate, which results in quenching of fluorescence emission due to excitonic interactions between the dyes. The hybridization of the FC target to the probe provides for dissociation of the aggregate as the dyes intercalate into the double stranded duplex, resulting in increased fluorescence. This work reports investigation of the dependence of the ratiometric signal on the type of linkage used to conjugate the dyes to the probe, the location of the dye along the length of the probe, and the distance between adjacent dye molecules. The limit of detection for 34mer and 90mer targets was found to be identical and was 10 nM (2 pmol), similar to analogous QD-FRET using labeled oligonucleotide target. The detection system could discriminate a one base pair mismatch (1BPM) target and was functional without substantial compromise of the signal in 75% serum. The 1BPM was found to reduce background signal, indicating that the structure of the mismatch affected the environment of the intercalating dyes.

Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids. Addendum

Science.gov (United States)

2009-08-01

Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit A. Evrensel...AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible... Magneto -rheological Fluid (MRF) iron nano-particles were synthesized using the reverse micelle technique and coated with poly(NIPAAm). The size

Fabrication of genetically engineered polypeptide@quantum dots hybrid nanogels for targeted imaging

Science.gov (United States)

Yang, Jie; Yao, Ming-Hao; Zhao, Dong-Hui; Zhang, Xiao-Shuai; Jin, Rui-Mei; Zhao, Yuan-Di; Liu, Bo

2017-08-01

Nanogels have been widely used as multifunctional drug delivery carriers because of high water content, biocompatibility, and high loading capability. We designed and biosynthesized two triblock artificial polypeptides PC10A and PC10ARGD as vehicles for encapsulating hydrophobic materials. These polypeptides can form nanogels by self-assembly when the concentration is below 2% ( w/ v). The physical properties of nanogels, including size, surface potential, and targeting domain, are able to be tuned. Hydrophobic materials from molecular size to nano-size can be loaded into the polypeptide nanogels to form hybrid nanogels. Hydrophobic quantum dots CdSe@ZnS below 10 nM were loaded into the polypeptide nanogels by ultrasonic treatment. Encapsulation endows hydrophobic QDs with good tunability of size, water solubility, stability, targeting, and biocompatibility. PC10ARGD nanogels and PC10ARGD@QDs hybrid nanogels showed excellent biocompatibility, which the cellular viabilities of HeLa and MCF-7 cells treated with 1% PC10ARGD nanogels and PC10ARGD@QDs hybrid nanogels contained 20 nM QDs were above 90 and 80%, respectively. PC10ARGD@QDs hybrid nanogels with an arginine-glycine-aspartic acid motif present efficient receptor-mediated endocytosis in α v β 3 overexpressing HeLa cells but not in the control MCF-7 cells as analyzed by confocal microscopy. These results demonstrate that such polypeptide nanogels as nanocarriers are expected to have great potential applications in biomedicine.

Chronic neural probe for simultaneous recording of single-unit, multi-unit, and local field potential activity from multiple brain sites

Science.gov (United States)

Pothof, F.; Bonini, L.; Lanzilotto, M.; Livi, A.; Fogassi, L.; Orban, G. A.; Paul, O.; Ruther, P.

2016-08-01

Objective. Drug resistant focal epilepsy can be treated by resecting the epileptic focus requiring a precise focus localisation using stereoelectroencephalography (SEEG) probes. As commercial SEEG probes offer only a limited spatial resolution, probes of higher channel count and design freedom enabling the incorporation of macro and microelectrodes would help increasing spatial resolution and thus open new perspectives for investigating mechanisms underlying focal epilepsy and its treatment. This work describes a new fabrication process for SEEG probes with materials and dimensions similar to clinical probes enabling recording single neuron activity at high spatial resolution. Approach. Polyimide is used as a biocompatible flexible substrate into which platinum electrodes and leads are integrated with a minimal feature size of 5 μm. The polyimide foils are rolled into the cylindrical probe shape at a diameter of 0.8 mm. The resulting probe features match those of clinically approved devices. Tests in saline solution confirmed the probe stability and functionality. Probes were implanted into the brain of one monkey (Macaca mulatta), trained to perform different motor tasks. Suitable configurations including up to 128 electrode sites allow the recording of task-related neuronal signals. Main results. Probes with 32 and 64 electrode sites were implanted in the posterior parietal cortex. Local field potentials and multi-unit activity were recorded as early as one hour after implantation. Stable single-unit activity was achieved for up to 26 days after implantation of a 64-channel probe. All recorded signals showed modulation during task execution. Significance. With the novel probes it is possible to record stable biologically relevant data over a time span exceeding the usual time needed for epileptic focus localisation in human patients. This is the first time that single units are recorded along cylindrical polyimide probes chronically implanted 22 mm deep into the

Preparation and biocompatibility evaluation of apatite/wollastonite-derived porous bioactive glass ceramic scaffolds

International Nuclear Information System (INIS)

Zhang Hua; Ye Xiaojian; Li Jiashun

2009-01-01

An apatite/wollastonite-derived (A/W) porous glass ceramic scaffold with highly interconnected pores was successfully fabricated by adding a plastic porosifier. The morphology, porosity and mechanical strength were characterized. The results showed that the glass ceramic scaffold with controllable pore size and porosity displayed open macropores. In addition, good in vitro bioactivity was found for the scaffold obtained by soaking it in simulated body fluid. Mesenchymal stem cells (MSCs) were cultured, expanded and seeded on the scaffold, and the adhesion and proliferation of MSCs were determined using MTT assay and environmental scanning electron microscopy (ESEM). The results revealed that the scaffold was biocompatible and had no negative effects on the MSCs in vitro. The in vivo biocompatibility and osteogenicity were investigated by implanting both the pure scaffold and the MSC/scaffold construct in rabbit mandibles and studying histologically. The results showed that the glass ceramic scaffold exhibited good biocompatibility and osteoconductivity. Moreover, the introduction of MSCs into the scaffold observably improved the efficiency of new bone formation, especially at the initial stage after implantation. However, the glass ceramic scaffold showed the same good biocompatibility and osteogenicity as the hybrid one at the later stage. These results indicate that porous bioactive scaffolds based on the original apatite-wollastonite glass ceramic fulfil the basic requirements of a bone tissue engineering scaffold.

Alginate/Poly(γ-glutamic Acid) Base Biocompatible Gel for Bone Tissue Engineering

Science.gov (United States)

Chan, Wing P.; Kung, Fu-Chen; Kuo, Yu-Lin; Yang, Ming-Chen; Lai, Wen-Fu Thomas

2015-01-01

A technique for synthesizing biocompatible hydrogels by cross-linking calcium-form poly(γ-glutamic acid), alginate sodium, and Pluronic F-127 was created, in which alginate can be cross-linked by Ca2+ from Ca–γ-PGA directly and γ-PGA molecules introduced into the alginate matrix to provide pH sensitivity and hemostasis. Mechanical properties, swelling behavior, and blood compatibility were investigated for each hydrogel compared with alginate and for γ-PGA hydrogel with the sodium form only. Adding F-127 improves mechanical properties efficiently and influences the temperature-sensitive swelling of the hydrogels but also has a minor effect on pH-sensitive swelling and promotes anticoagulation. MG-63 cells were used to test biocompatibility. Gelation occurred gradually through change in the elastic modulus as the release of calcium ions increased over time and caused ionic cross-linking, which promotes the elasticity of gel. In addition, the growth of MG-63 cells in the gel reflected nontoxicity. These results showed that this biocompatible scaffold has potential for application in bone materials. PMID:26504784

Chemically resistant, biocompatible and microstructured surface protection

International Nuclear Information System (INIS)

Hoffmann, W.; Pham, M.T.; Hueller, J.

1984-01-01

Subject of the invention are chemicallly resistant, biocompatible, and microstructured surface protective coatings of electronic elements and sensors including chemical sensors. Such coatings consist of a radiation-modified organic substance made of a microlithographic material. Modification can be achieved by irradiation with ions, atoms or molecules having an energy between 1 KeV and 1 MeV and a flux between 10 13 and 10 18 particles per cm 2

Combining metabolic engineering and biocompatible chemistry for high-yield production of homo-diacetyl and homo-(S,S)-2,3-butanediol

DEFF Research Database (Denmark)

Liu, Jianming; Chan, Siu Hung Joshua; Brock-Nannestad, Theis

2016-01-01

Biocompatible chemistry is gaining increasing attention because of its potential within biotechnology for expanding the repertoire of biological transformations carried out by enzymes. Here we demonstrate how biocompatible chemistry can be used for synthesizing valuable compounds as well as for l...... of 82%. The diacetyl and S-BDO production rates and yields obtained are the highest ever reported, demonstrating the promising combination of metabolic engineering and biocompatible chemistry as well as the great potential of L. lactis as a new production platform.......Biocompatible chemistry is gaining increasing attention because of its potential within biotechnology for expanding the repertoire of biological transformations carried out by enzymes. Here we demonstrate how biocompatible chemistry can be used for synthesizing valuable compounds as well...

Biocompatibility of single-walled carbon nanotube composites for bone regeneration.

Science.gov (United States)

Gupta, A; Liberati, T A; Verhulst, S J; Main, B J; Roberts, M H; Potty, A G R; Pylawka, T K; El-Amin Iii, S F

2015-05-01

The purpose of this study was to evaluate in vivo biocompatibility of novel single-walled carbon nanotubes (SWCNT)/poly(lactic-co-glycolic acid) (PLAGA) composites for applications in bone and tissue regeneration. A total of 60 Sprague-Dawley rats (125 g to 149 g) were implanted subcutaneously with SWCNT/PLAGA composites (10 mg SWCNT and 1gm PLAGA 12 mm diameter two-dimensional disks), and at two, four, eight and 12 weeks post-implantation were compared with control (Sham) and PLAGA (five rats per group/point in time). Rats were observed for signs of morbidity, overt toxicity, weight gain and food consumption, while haematology, urinalysis and histopathology were completed when the animals were killed. No mortality and clinical signs were observed. All groups showed consistent weight gain, and the rate of gain for each group was similar. All groups exhibited a similar pattern for food consumption. No difference in urinalysis, haematology, and absolute and relative organ weight was observed. A mild to moderate increase in the summary toxicity (sumtox) score was observed for PLAGA and SWCNT/PLAGA implanted animals, whereas the control animals did not show any response. Both PLAGA and SWCNT/PLAGA showed a significantly higher sumtox score compared with the control group at all time intervals. However, there was no significant difference between PLAGA and SWCNT/PLAGA groups. Our results demonstrate that SWCNT/PLAGA composites exhibited in vivo biocompatibility similar to the Food and Drug Administration approved biocompatible polymer, PLAGA, over a period of 12 weeks. These results showed potential of SWCNT/PLAGA composites for bone regeneration as the low percentage of SWCNT did not elicit a localised or general overt toxicity. Following the 12-week exposure, the material was considered to have an acceptable biocompatibility to warrant further long-term and more invasive in vivo studies. Cite this article: Bone Joint Res 2015;4:70-7. ©2015 The British Editorial

Effects of surface finishing conditions on the biocompatibility of a nickel-chromium dental casting alloy.

LENUS (Irish Health Repository)

McGinley, Emma Louise

2011-07-01

To assess the effects of surface finishing condition (polished or alumina particle air abraded) on the biocompatibility of direct and indirect exposure to a nickel-chromium (Ni-Cr) d.Sign®10 dental casting alloy on oral keratinocytes. Biocompatibility was performed by assessing cellular viability and morphology, metabolic activity, cellular toxicity and presence of inflammatory cytokine markers.

Estimating the similarity of alternative Affymetrix probe sets using transcriptional networks

Science.gov (United States)

2013-01-01

Background The usefulness of the data from Affymetrix microarray analysis depends largely on the reliability of the files describing the correspondence between probe sets, genes and transcripts. Particularly, when a gene is targeted by several probe sets, these files should give information about the similarity of each alternative probe set pair. Transcriptional networks integrate the multiple correlations that exist between all probe sets and supply much more information than a simple correlation coefficient calculated for two series of signals. In this study, we used the PSAWN (Probe Set Assignment With Networks) programme we developed to investigate whether similarity of alternative probe sets resulted in some specific properties. Findings PSAWNpy delivered a full textual description of each probe set and information on the number and properties of secondary targets. PSAWNml calculated the similarity of each alternative probe set pair and allowed finding relationships between similarity and localisation of probes in common transcripts or exons. Similar alternative probe sets had very low negative correlation, high positive correlation and similar neighbourhood overlap. Using these properties, we devised a test that allowed grouping similar probe sets in a given network. By considering several networks, additional information concerning the similarity reproducibility was obtained, which allowed defining the actual similarity of alternative probe set pairs. In particular, we calculated the common localisation of probes in exons and in known transcripts and we showed that similarity was correctly correlated with them. The information collected on all pairs of alternative probe sets in the most popular 3’ IVT Affymetrix chips is available in tabular form at http://bns.crbm.cnrs.fr/download.html. Conclusions These processed data can be used to obtain a finer interpretation when comparing microarray data between biological conditions. They are particularly well

Estimating the similarity of alternative Affymetrix probe sets using transcriptional networks.

Science.gov (United States)

Bellis, Michel

2013-03-21

The usefulness of the data from Affymetrix microarray analysis depends largely on the reliability of the files describing the correspondence between probe sets, genes and transcripts. Particularly, when a gene is targeted by several probe sets, these files should give information about the similarity of each alternative probe set pair. Transcriptional networks integrate the multiple correlations that exist between all probe sets and supply much more information than a simple correlation coefficient calculated for two series of signals. In this study, we used the PSAWN (Probe Set Assignment With Networks) programme we developed to investigate whether similarity of alternative probe sets resulted in some specific properties. PSAWNpy delivered a full textual description of each probe set and information on the number and properties of secondary targets. PSAWNml calculated the similarity of each alternative probe set pair and allowed finding relationships between similarity and localisation of probes in common transcripts or exons. Similar alternative probe sets had very low negative correlation, high positive correlation and similar neighbourhood overlap. Using these properties, we devised a test that allowed grouping similar probe sets in a given network. By considering several networks, additional information concerning the similarity reproducibility was obtained, which allowed defining the actual similarity of alternative probe set pairs. In particular, we calculated the common localisation of probes in exons and in known transcripts and we showed that similarity was correctly correlated with them. The information collected on all pairs of alternative probe sets in the most popular 3' IVT Affymetrix chips is available in tabular form at http://bns.crbm.cnrs.fr/download.html. These processed data can be used to obtain a finer interpretation when comparing microarray data between biological conditions. They are particularly well adapted for searching 3' alternative

Biocompatibility assessment of rice husk-derived biogenic silica nanoparticles for biomedical applications

Energy Technology Data Exchange (ETDEWEB)

Alshatwi, Ali A., E-mail: alshatwi@ksu.edu.sa; Athinarayanan, Jegan; Periasamy, Vaiyapuri Subbarayan

2015-02-01

Synthetic forms of silica have low biocompatibility, whereas biogenic forms have myriad beneficial effects in current toxicological applications. Among the various sources of biogenic silica, rice husk is considered a valuable agricultural biomass material and a cost-effective resource that can provide biogenic silica for biomedical applications. In the present study, highly pure biogenic silica nanoparticles (bSNPs) were successfully harvested from rice husks using acid digestion under pressurized conditions at 120 °C followed by a calcination process. The obtained bSNPs were subjected to phase identification analysis using X-ray diffraction, which revealed the amorphous nature of the bSNPs. The morphologies of the bSNPs were observed using transmission electron microscopy (TEM), which revealed spherical particles 10 to 30 nm in diameter. Furthermore, the biocompatibility of the bSNPs with human lung fibroblast cells (hLFCs) was investigated using a viability assay and assessing cellular morphological changes, intracellular ROS generation, mitochondrial transmembrane potential and oxidative stress-related gene expression. Our results revealed that the bSNPs did not have any significant incompatibility in these in vitro cell-based approaches. These preliminary findings suggest that bSNPs are biocompatible, could be the best alternative to synthetic forms of silica and are applicable to food additive and biomedical applications. - Highlights: • Simple, rapid and convenient process • Amorphous and spherical with 10–30 nm size SiO{sub 2} nanoparticles were fabricated. • Biogenic silica nanoparticles showed biocompatibility. • bSNPs are an alternative to synthetic forms of silica.

Development of novel biocompatible hybrid nanocomposites based on polyurethane-silica prepared by sol gel process

Energy Technology Data Exchange (ETDEWEB)

Rashti, Ali [Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Yahyaei, Hossein [Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Firoozi, Saman [Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ramezani, Sara [Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Rahiminejad, Ali [Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Karimi, Roya [Department of Tissue Engineering and Applied Cell Science, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Farzaneh, Khadijeh [Tehran Heart Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Mohseni, Mohsen [Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Ghanbari, Hossein, E-mail: hghanbari@tums.ac.ir [Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Tehran Heart Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Medical Biomaterials Research Center, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

2016-12-01

Due to high biocompatibility, polyurethane has found many applications, particularly in development of biomedical devices. A new nanocomposite based on thermoset polyurethane and silica nanoparticles was synthesized using sol-gel method. Sol-gel process was fulfilled in two acidic and basic conditions by using tetraethylorthosilicate (TEOS) and trimethoxyisocyanatesilane as precursors. The hybrid films characterized for mechanical and surface properties using tensile strength, contact angle, ATR-FTIR and scanning electron microscopy. Biocompatibility and cytotoxicity of the hybrids were assessed using standard MTT, LDH and TUNEL assays. The results revealed that incorporation of silica nanoparticles was significantly improved tensile strength and mechanical properties of the hybrids. Based on the contact angle results, silica nanoparticles increased hydrophilicity of the hybrids. Biocompatibility by using human lung epithelial cell line (MRC-5) demonstrated that the hybrids were significantly less cytotoxic compared to pristine polymer as tested by MTT and LDH assays. TUNEL assay revealed no signs of apoptosis in all tested samples. The results of this study demonstrated that incorporation of silica nanoparticles into polyurethane lead to the enhancement of biocompatibility, indicating that these hybrids could potentially be used in biomedical field in particular as a new coating for medical implants. - Highlights: • Nanocomposites based on polyurethane and nanosilica prepared by sol-gel method fabricated • Addition of inorganic phase improved mechanical properties. • Nanosilica prepared by sol-gel method increased hydrophilicity. • By adding nanosilica to polyurethane biocompatibility increased significantly.

ProSeeK: a web server for MLPA probe design.

Science.gov (United States)

Pantano, Lorena; Armengol, Lluís; Villatoro, Sergi; Estivill, Xavier

2008-11-28

The technological evolution of platforms for detecting genome-wide copy number imbalances has allowed the discovery of an unexpected amount of human sequence that is variable in copy number among individuals. This type of human variation can make an important contribution to human diversity and disease susceptibility. Multiplex Ligation-dependent Probe Amplification (MLPA) is a targeted method to assess copy number differences for up to 40 genomic loci in one single experiment. Although specific MLPA assays can be ordered from MRC-Holland (the proprietary company of the MLPA technology), custom designs are also developed in many laboratories worldwide. After our own experience, an important drawback of custom MLPA assays is the time spent during the design of the specific oligonucleotides that are used as probes. Due to the large number of probes included in a single assay, a number of restrictions need to be met in order to maximize specificity and to increase success likelihood. We have developed a web tool for facilitating and optimising custom probe design for MLPA experiments. The algorithm only requires the target sequence in FASTA format and a set of parameters, that are provided by the user according to each specific MLPA assay, to identify the best probes inside the given region. To our knowledge, this is the first available tool for optimizing custom probe design of MLPA assays. The ease-of-use and speed of the algorithm dramatically reduces the turn around time of probe design. ProSeeK will become a useful tool for all laboratories that are currently using MLPA in their research projects for CNV studies.

ProSeeK: A web server for MLPA probe design

Directory of Open Access Journals (Sweden)

Villatoro Sergi

2008-11-01

Full Text Available Abstract Background The technological evolution of platforms for detecting genome-wide copy number imbalances has allowed the discovery of an unexpected amount of human sequence that is variable in copy number among individuals. This type of human variation can make an important contribution to human diversity and disease susceptibility. Multiplex Ligation-dependent Probe Amplification (MLPA is a targeted method to assess copy number differences for up to 40 genomic loci in one single experiment. Although specific MLPA assays can be ordered from MRC-Holland (the proprietary company of the MLPA technology, custom designs are also developed in many laboratories worldwide. After our own experience, an important drawback of custom MLPA assays is the time spent during the design of the specific oligonucleotides that are used as probes. Due to the large number of probes included in a single assay, a number of restrictions need to be met in order to maximize specificity and to increase success likelihood. Results We have developed a web tool for facilitating and optimising custom probe design for MLPA experiments. The algorithm only requires the target sequence in FASTA format and a set of parameters, that are provided by the user according to each specific MLPA assay, to identify the best probes inside the given region. Conclusion To our knowledge, this is the first available tool for optimizing custom probe design of MLPA assays. The ease-of-use and speed of the algorithm dramatically reduces the turn around time of probe design. ProSeeK will become a useful tool for all laboratories that are currently using MLPA in their research projects for CNV studies.

An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones.

Science.gov (United States)

Nuss, Katja M R; Auer, Joerg A; Boos, Alois; von Rechenberg, Brigitte

2006-08-15

The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials.

An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

Directory of Open Access Journals (Sweden)

Boos Alois

2006-08-01

Full Text Available Abstract Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Results This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. Conclusion This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials.

An animal model in sheep for biocompatibility testing of biomaterials in cancellous bones

Science.gov (United States)

Nuss, Katja MR; Auer, Joerg A; Boos, Alois; Rechenberg, Brigitte von

2006-01-01

Background The past years have seen the development of many synthetic bone replacements. To test their biocompatibility and ability for osseointegration, osseoinduction and -conduction requires their placement within bone preferably in an animal experiment of a higher species. Methods A suitable experimental animal model in sheep with drill holes of 8 mm diameter and 13 mm depth within the proximal and distal humerus and femur for testing biocompatibility issues is introduced. Results This present sheep model allows the placing of up to 8 different test materials within one animal and because of the standardization of the bone defect, routine evaluation by means of histomorphometry is easily conducted. This method was used successfully in 66 White Alpine Sheep. When the drill holes were correctly placed no complications such as spontaneous fractures were encountered. Conclusion This experimental animal model serves an excellent basis for testing the biocompatibility of novel biomaterials to be used as bone replacement or new bone formation enhancing materials. PMID:16911787

A Single Electrochemical Probe Used for Analysis of Multiple Nucleic Acid Sequences

Science.gov (United States)

Mills, Dawn M.; Calvo-Marzal, Percy; Pinzon, Jeffer M.; Armas, Stephanie; Kolpashchikov, Dmitry M.; Chumbimuni-Torres, Karin Y.

2017-01-01

Electrochemical hybridization sensors have been explored extensively for analysis of specific nucleic acids. However, commercialization of the platform is hindered by the need for attachment of separate oligonucleotide probes complementary to a RNA or DNA target to an electrode’s surface. Here we demonstrate that a single probe can be used to analyze several nucleic acid targets with high selectivity and low cost. The universal electrochemical four-way junction (4J)-forming (UE4J) sensor consists of a universal DNA stem-loop (USL) probe attached to the electrode’s surface and two adaptor strands (m and f) which hybridize to the USL probe and the analyte to form a 4J associate. The m adaptor strand was conjugated with a methylene blue redox marker for signal ON sensing and monitored using square wave voltammetry. We demonstrated that a single sensor can be used for detection of several different DNA/RNA sequences and can be regenerated in 30 seconds by a simple water rinse. The UE4J sensor enables a high selectivity by recognition of a single base substitution, even at room temperature. The UE4J sensor opens a venue for a re-useable universal platform that can be adopted at low cost for the analysis of DNA or RNA targets. PMID:29371782

Vectorization of copper complexes via biocompatible and biodegradable PLGA nanoparticles.

Science.gov (United States)

Courant, T; Roullin, V G; Cadiou, C; Delavoie, F; Molinari, M; Andry, M C; Gafa, V; Chuburu, F

2010-04-23

A double emulsion-solvent diffusion approach with fully biocompatible materials was used to encapsulate copper complexes within biodegradable nanoparticles, for which the release kinetics profiles have highlighted their potential use for a prolonged circulating administration.

Vectorization of copper complexes via biocompatible and biodegradable PLGA nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Courant, T; Roullin, V G; Andry, M C [Institut de Chimie Moleculaire de Reims, CNRS UMR 6229, UFR Pharmacie Reims, 51 rue Cognacq-Jay, F-51100 Reims (France); Cadiou, C; Chuburu, F [Institut de Chimie Moleculaire de Reims, CNRS UMR 6229, UFR des Sciences Exactes et Naturelles, Batiment 18-Europol' Agro, BP 1039, F-51687 Reims Cedex 2 (France); Delavoie, F [Laboratoire de Microscopie Electronique Analytique, INSERM UMRS 926, 21 rue Clement Ader, F-51685 Reims Cedex 2 (France); Molinari, M [Laboratoire de Microscopies et d' Etudes des Nanostructures, UFR des Sciences, Universite de Reims Champagne-Ardenne, 21 rue Clement Ader, F-51685 Reims Cedex 2 (France); Gafa, V, E-mail: gaelle.roullin@univ-reims.fr, E-mail: francoise.chuburu@univ-reims.fr [EA4303 ' Inflammation et Immunite de l' Epithelium Respiratoire' , IFR53, UFR de Pharmacie, Universite de Reims Champagne-Ardenne, 51 rue Cognacq-Jay, F-51100 Reims (France)

2010-04-23

A double emulsion-solvent diffusion approach with fully biocompatible materials was used to encapsulate copper complexes within biodegradable nanoparticles, for which the release kinetics profiles have highlighted their potential use for a prolonged circulating administration.

Vectorization of copper complexes via biocompatible and biodegradable PLGA nanoparticles

International Nuclear Information System (INIS)

Courant, T; Roullin, V G; Andry, M C; Cadiou, C; Chuburu, F; Delavoie, F; Molinari, M; Gafa, V

2010-01-01

A double emulsion-solvent diffusion approach with fully biocompatible materials was used to encapsulate copper complexes within biodegradable nanoparticles, for which the release kinetics profiles have highlighted their potential use for a prolonged circulating administration.

Functionalization of titanium surface with chitosan via silanation: 3D CLSM imaging of cell biocompatibility behaviour.

Science.gov (United States)

Attik, G N; D'Almeida, M; Toury, B; Grosgogeat, B

2013-09-16

Biocompatibility ranks as one of the most important properties of dental materials. One of the criteria for biocompatibility is the absence of material toxicity to cells, according to the ISO 7405 and 10993 recommendations. Among numerous available methods for toxicity assessment; 3-dimensional Confocal Laser Scanning Microscopy (3D CLSM) imaging was chosen because it provides an accurate and sensitive index of living cell behavior in contact with chitosan coated tested implants. The purpose of this study was to investigate the in vitro biocompatibility of functionalized titanium with chitosan via a silanation using sensitive and innovative 3D CLSM imaging as an investigation method for cytotoxicity assessment. The biocompatibility of four samples (controls cells, TA6V, TA6V-TESBA and TA6V-TESBAChitosan) was compared in vitro after 24h of exposure. Confocal imaging was performed on cultured human gingival fibroblast (HGF1) like cells using Live/Dead® staining. Image series were obtained with a FV10i confocal biological inverted system and analyzed with FV10-ASW 3.1 Software (Olympus France). Image analysis showed no cytotoxicity in the presence of the three tested substrates after 24 h of contact. A slight decrease of cell viability was found in contact with TA6V-TESBA with and without chitosan compared to negative control cells. Our findings highlighted the use of 3D CLSM confocal imaging as a sensitive method to evaluate qualitatively and quantitatively the biocompatibility behavior of functionalized titanium with chitosan via a silanation. The biocompatibility of the new functionalized coating to HGF1 cells is as good as the reference in biomedical device implantation TA6V.

Use of SU8 as a stable and biocompatible adhesion layer for gold bioelectrodes.

Science.gov (United States)

Matarèse, Bruno F E; Feyen, Paul L C; Falco, Aniello; Benfenati, Fabio; Lugli, Paolo; deMello, John C

2018-04-03

Gold is the most widely used electrode material for bioelectronic applications due to its high electrical conductivity, good chemical stability and proven biocompatibility. However, it adheres only weakly to widely used substrate materials such as glass and silicon oxide, typically requiring the use of a thin layer of chromium between the substrate and the metal to achieve adequate adhesion. Unfortunately, this approach can reduce biocompatibility relative to pure gold films due to the risk of the underlying layer of chromium becoming exposed. Here we report on an alternative adhesion layer for gold and other metals formed from a thin layer of the negative-tone photoresist SU-8, which we find to be significantly less cytotoxic than chromium, being broadly comparable to bare glass in terms of its biocompatibility. Various treatment protocols for SU-8 were investigated, with a view to attaining high transparency and good mechanical and biochemical stability. Thermal annealing to induce partial cross-linking of the SU-8 film prior to gold deposition, with further annealing after deposition to complete cross-linking, was found to yield the best electrode properties. The optimized glass/SU8-Au electrodes were highly transparent, resilient to delamination, stable in biological culture medium, and exhibited similar biocompatibility to glass.

Biocompatibility of GaSb thin films grown by RF magnetron sputtering

Science.gov (United States)

Nishimoto, Naoki; Fujihara, Junko; Yoshino, Katsumi

2017-07-01

GaSb may be suitable for biological applications, such as cellular sensors and bio-medical instrumentation because of its low toxicity compared with As (III) compounds and its band gap energy. Therefore, the biocompatibility and the film properties under physiological conditions were investigated for GaSb thin films with or without a surface coating. GaSb thin films were grown on quartz substrates by RF magnetron sputtering, and then coated with (3-mercaptopropyl) trimethoxysilane (MPT). The electrical properties, surface morphology, and crystal structure of the GaSb thin film were unaffected by the MPT coating. The cell viability assay suggested that MPT-coated GaSb thin films are biocompatible. Bare GaSb was particularly unstable in pH9 buffer. Ga elution was prevented by the MPT coating, although the Ga concentration in the pH 9 buffer was higher than that in the other solutions. The surface morphology and crystal structure were not changed by exposure to the solutions, except for the pH 9 buffer, and the thin film properties of MPT-coated GaSb exposed to distilled water and H2O2 in saline were maintained. These results indicate that MPT-coated GaSb thin films are biocompatible and could be used for temporary biomedical devices.

BIOCOMPATIBLE FLUORESCENT MICROSPHERES: SAFE PARTICLES FOR MATERIAL PENETRATION STUDIES

Energy Technology Data Exchange (ETDEWEB)

farquar, G; Leif, R

2008-09-12

Biocompatible polymers with hydrolyzable chemical bonds are being used to produce safe, non-toxic fluorescent microspheres for material penetration studies. The selection of polymeric materials depends on both biocompatibility and processability, with tailored fluorescent properties depending on specific applications. Microspheres are composed of USFDA-approved biodegradable polymers and non-toxic fluorophores and are therefore suitable for tests where human exposure is possible. Micropheres are being produced which contain unique fluorophores to enable discrimination from background aerosol particles. Characteristics that affect dispersion and adhesion can be modified depending on use. Several different microsphere preparation methods are possible, including the use of a vibrating orifice aerosol generator (VOAG), a Sono-Tek atomizer, an emulsion technique, and inkjet printhead. The advantages and disadvantages of each method will be presented and discussed in greater detail along with fluorescent and charge properties of the aerosols. Applications for the fluorescent microspheres include challenges for biodefense system testing, calibrants for biofluorescence sensors, and particles for air dispersion model validation studies.

A Conjugate of Pentamethine Cyanine and 18F as a Positron Emission Tomography/Near-Infrared Fluorescence Probe for Multimodality Tumor Imaging

Directory of Open Access Journals (Sweden)

Fei-Fei An

2017-06-01

Full Text Available The novel synthesis of a dual-modality, pentamethine cyanine (Cy5 fluorescent, 18F positron emission tomography (PET imaging probe is reported. The probe shows a large extinction coefficient and large quantum yield in the biologically transparent, near-infrared window (650–900 nm for in vivo fluorescent imaging. This fluorophore bears the isotope, 18F, giving a 18F-PET/near-infrared fluorescent (NIRF, bi-modal imaging probe, that combines the long-term stability of NIRF and the unlimited penetration depth of PET imaging. The bi-modal probe is labeled with 18F in a quick, one-step reaction, which is important in working with the rapid decay of 18F. The bi-modal probe bears a free carboxyl group, highlighting a PET/NIRF synthon that can be conjugated onto many advanced biomolecules for biomarker-specific in vivo dual-modal PET/NIR tumor imaging, confocal histology, and utility in multi-fluorophore, fluorescence-guided surgery. Its potential in vivo biocompatibility is explored in a quick proof-of-principal in vivo study. The dye is delivered to A549 xenograft flank-tumors to generate PET and NIRF signals at the tumor site. The tumor distribution is confirmed in ex vivo gamma counting and imaging. Pentamethine cyanine (Cy5 has the ability to preferentially accumulate in tumor xenografts. We substitute the PET/NIRF probe for Cy5, and explore this phenomenon.

Probing gas-surface interactions with a molecular beam

International Nuclear Information System (INIS)

Spruit, M.E.M.

1988-01-01

The dynamics of direct scattering, trapping and sticking in molecular beam scattering is probed. The O 2 /Ag interaction was chosen, using the close-packed (111) plane of Ag as target surface. 170 refs.; 22 figs.; 3 tabs

Electrostatically driven resonance energy transfer in "cationic" biocompatible indium phosphide quantum dots.

Science.gov (United States)

Devatha, Gayathri; Roy, Soumendu; Rao, Anish; Mallick, Abhik; Basu, Sudipta; Pillai, Pramod P

2017-05-01

Indium Phosphide Quantum Dots (InP QDs) have emerged as an alternative to toxic metal ion based QDs in nanobiotechnology. The ability to generate cationic surface charge, without compromising stability and biocompatibility, is essential in realizing the full potential of InP QDs in biological applications. We have addressed this challenge by developing a place exchange protocol for the preparation of cationic InP/ZnS QDs. The quaternary ammonium group provides the much required permanent positive charge and stability to InP/ZnS QDs in biofluids. The two important properties of QDs, namely bioimaging and light induced resonance energy transfer, are successfully demonstrated in cationic InP/ZnS QDs. The low cytotoxicity and stable photoluminescence of cationic InP/ZnS QDs inside cells make them ideal candidates as optical probes for cellular imaging. An efficient resonance energy transfer ( E ∼ 60%) is observed, under physiological conditions, between the cationic InP/ZnS QD donor and anionic dye acceptor. A large bimolecular quenching constant along with a linear Stern-Volmer plot confirms the formation of a strong ground state complex between the cationic InP/ZnS QDs and the anionic dye. Control experiments prove the role of electrostatic attraction in driving the light induced interactions, which can rightfully form the basis for future nano-bio studies between cationic InP/ZnS QDs and anionic biomolecules.

PEG capped methotrexate silver nanoparticles for efficient anticancer activity and biocompatibility.

Science.gov (United States)

Muhammad, Zarmina; Raza, Abida; Ghafoor, Sana; Naeem, Ayesha; Naz, Syeda Sohaila; Riaz, Sundus; Ahmed, Wajiha; Rana, Nosheen Fatima

2016-08-25

Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific properties of either component. These benefits include, increase in the drug blood retention time, reduced efflux, additional toxicity and targeted delivery. Methotrexate (MTX) is clinically used for cancer treatment. Higher dosage of MTX results in hepatic and renal toxicity. In this study methotrexate silver nanoparticles (Ag-MTX) coated with polyethylene glycol (PEG) are synthesized and characterized. Their anticancer activity and biocompatibility is also evaluated. Ag-MTX nanoparticles are synthesized by chemical reduction method. They are characterized by Ultraviolet-Visible Spectroscopy and Fourier Transform Infrared Spectroscopy. Average size of PEG coated Ag-MTX nanoparticles (PEG-Ag-MTX nanoparticles) is 12nm. These particles exhibited improved anticancer activity against MCF-7 cell line. Hemolytic activity of these particles was significantly less than MTX. PEG-Ag-MTX nanoparticles are potential nanocarrier of methotrexate which may offer MTX based cancer treatment with reduced side effects. In-vivo investigations should be carried out to explore them in detail. Copyright © 2016 Elsevier B.V. All rights reserved.

RGD peptide-targeted polyethylenimine-entrapped gold nanoparticles for targeted CT imaging of an orthotopic model of human hepatocellular carcinoma

Science.gov (United States)

Zhou, Benqing; Wang, Meng; Zhou, Feifan; Song, Jun; Qu, Junle; Chen, Wei R.

2018-02-01

We report the synthesis and characterization of arginine-glycine-aspartic acid (RGD) peptide-targeted polyethylenimine (PEI)-entrapped gold nanoparticles (RGD-Au PENPs) for targeted CT imaging of hepatic carcinomas in situ. In this work, PEI sequentially modified with polyethylene glycol (PEG), and RGD linked-PEG was used as a nanoplatform to prepare AuNPs, followed by complete acetylation of PEI surface amines. We showed that the designed RGD-Au PENPs were colloidally stable and biocompatible in the given concentration range, and could be specifically taken up by αvβ3 integrin-overexpressing liver cancer cells in vitro. Furthermore, in vivo CT imaging results revealed that the particles displayed a great contrast enhancement of hepatic carcinomas region, and could target to hepatic carcinomas region in situ. With the proven biodistribution and histological examinations in vivo, the synthesized RGD-Au PENPs show a great formulation to be used as a contrast agent for targeted CT imaging of different αvβ3 integrin receptoroverexpressing tumors.

Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups

Science.gov (United States)

Ekkapongpisit, Maneerat; Giovia, Antonino; Follo, Carlo; Caputo, Giuseppe; Isidoro, Ciro

2012-01-01

Background and methods Nanoparticles engineered to carry both a chemotherapeutic drug and a sensitive imaging probe are valid tools for early detection of cancer cells and to monitor the cytotoxic effects of anticancer treatment simultaneously. Here we report on the effect of size (10–30 nm versus 50 nm), type of material (mesoporous silica versus polystyrene), and surface charge functionalization (none, amine groups, or carboxyl groups) on biocompatibility, uptake, compartmentalization, and intracellular retention of fluorescently labeled nanoparticles in cultured human ovarian cancer cells. We also investigated the involvement of caveolae in the mechanism of uptake of nanoparticles. Results We found that mesoporous silica nanoparticles entered via caveolae-mediated endocytosis and reached the lysosomes; however, while the 50 nm nanoparticles permanently resided within these organelles, the 10 nm nanoparticles soon relocated in the cytoplasm. Naked 10 nm mesoporous silica nanoparticles showed the highest and 50 nm carboxyl-modified mesoporous silica nanoparticles the lowest uptake rates, respectively. Polystyrene nanoparticle uptake also occurred via a caveolae-independent pathway, and was negatively affected by serum. The 30 nm carboxyl-modified polystyrene nanoparticles did not localize in lysosomes and were not toxic, while the 50 nm amine-modified polystyrene nanoparticles accumulated within lysosomes and eventually caused cell death. Ovarian cancer cells expressing caveolin-1 were more likely to endocytose these nanoparticles. Conclusion These data highlight the importance of considering both the physicochemical characteristics (ie, material, size and surface charge on chemical groups) of nanoparticles and the biochemical composition of the cell membrane when choosing the most suitable nanotheranostics for targeting cancer cells. PMID:22904626

Surface-enhanced Raman scattering based nonfluorescent probe for multiplex DNA detection.

Science.gov (United States)

Sun, Lan; Yu, Chenxu; Irudayaraj, Joseph

2007-06-01

To provide rapid and accurate detection of DNA markers in a straightforward, inexpensive, and multiplex format, an alternative surface-enhanced Raman scattering based probe was designed and fabricated to covalently attach both DNA probing sequence and nonfluorescent Raman tags to the surface of gold nanoparticles (DNA-AuP-RTag). The intensity of Raman signal of the probes could be controlled through the surface coverage of the nonfluorescent Raman tags (RTags). Detection sensitivity of these probes could be optimized by fine-tuning the amount of DNA molecules and RTags on the probes. Long-term stability of the DNA-AuP-RTag probes was found to be good (over 3 months). Excellent multiplexing capability of the DNA-AuP-RTag scheme was demonstrated by simultaneous identification of up to eight probes in a mixture. Detection of hybridization of single-stranded DNA to its complementary targets was successfully accomplished with a long-term goal to use nonfluorescent RTags in a Raman-based DNA microarray platform.

A Novel “Off-On” Fluorescent Probe Based on Carbon Nitride Nanoribbons for the Detection of Citrate Anion and Live Cell Imaging

Directory of Open Access Journals (Sweden)

Yanling Hu

2018-04-01

Full Text Available A novel fluorescent “off-on” probe based on carbon nitride (C3N4 nanoribbons was developed for citrate anion (C6H5O73− detection. The fluorescence of C3N4 nanoribbons can be quenched by Cu2+ and then recovered by the addition of C6H5O73−, because the chelation between C6H5O73− and Cu2+ blocks the electron transfer between Cu2+ and C3N4 nanoribbons. The turn-on fluorescent sensor using this fluorescent “off-on” probe can detect C6H5O73− rapidly and selectively, showing a wide detection linear range (1~400 μM and a low detection limit (0.78 μM in aqueous solutions. Importantly, this C3N4 nanoribbon-based “off-on” probe exhibits good biocompatibility and can be used as fluorescent visualizer for exogenous C6H5O73− in HeLa cells.

Beyond attentional bias: a perceptual bias in a dot-probe task.

Science.gov (United States)

Bocanegra, Bruno R; Huijding, Jorg; Zeelenberg, René

2012-12-01

Previous dot-probe studies indicate that threat-related face cues induce a bias in spatial attention. Independently of spatial attention, a recent psychophysical study suggests that a bilateral fearful face cue improves low spatial-frequency perception (LSF) and impairs high spatial-frequency perception (HSF). Here, we combine these separate lines of research within a single dot-probe paradigm. We found that a bilateral fearful face cue, compared with a bilateral neutral face cue, speeded up responses to LSF targets and slowed down responses to HSF targets. This finding is important, as it shows that emotional cues in dot-probe tasks not only bias where information is preferentially processed (i.e., an attentional bias in spatial location), but also bias what type of information is preferentially processed (i.e., a perceptual bias in spatial frequency). PsycINFO Database Record (c) 2012 APA, all rights reserved.

Biocompatibility and tissue regenerating capacity of crosslinked dermal sheep collagen

NARCIS (Netherlands)

van Wachem, P.B.; van Luyn, M.J.A.; Olde Damink, L.H.H.; Olde damink, L.H.H.; Dijkstra, Pieter J.; Feijen, Jan; Nieuwenhuis, P.

1994-01-01

The biocompatibility and tissue regenerating capacity of four crosslinked dermal sheep collagens (DSC) was studied. In vitro, the four DSC versions were found to be noncytotoxic or very low in cytoxicity. After subcutaneous implantation in rats, hexamethylenediisocyanatecrcrosslinked DSC (HDSC)

Material properties and in vitro biocompatibility of a newly developed bone cement

Directory of Open Access Journals (Sweden)

Elke Mitzner

2009-01-01

Full Text Available In this study mechanical properties and biocompatibility (In Vitro of a new bone cement were investigated. A new platform technology named COOL is a variable composite of dissolved, chemically modified PMMA and different bioceramics. COOL cures at body temperature via a classical cementation reaction. Compressive strengths ranging from 3.6 ± 0.8 to 62.8 ± 1.3 MPa and bending strengths ranging from 9.9 ± 2.4 to 26.4 ± 3.0 MPa were achieved with different COOL formulations. Porosity varied between 31 and 43%. Varying the components of each formulation mechanical properties and porosity could be adjusted. In Vitro biocompatibility studies with primary human osteoblasts (pHOB in direct contact with different COOL formulations, did not reveal any signs of toxicity. In contrast to Refobacin® R, cells incubated with COOL showed similar density, viability and ALP activity compared to control, if specimen were added immediately to the cell monolayer after preparation. In conclusion, COOL has promising mechanical properties in combination with high biocompatibility In Vitro and combines different advantages of both CPCs and PMMA cements by avoiding some of the respective shortcomings.

Polycrystalline Silicon: a Biocompatibility Assay

International Nuclear Information System (INIS)

Pecheva, E.; Fingarova, D.; Pramatarova, L.; Hikov, T.; Laquerriere, P.; Bouthors, Sylvie; Dimova-Malinovska, D.; Montgomery, P.

2010-01-01

Polycrystalline silicon (poly-Si) layers were functionalized through the growth of biomimetic hydroxyapatite (HA) on their surface. HA is the mineral component of bones and teeth and thus possesses excellent bioactivity and biocompatibility. MG-63 osteoblast-like cells were cultured on both HA-coated and un-coated poly-Si surfaces for 1, 3, 5 and 7 days and toxicity, proliferation and cell morphology were investigated. The results revealed that the poly-Si layers were bioactive and compatible with the osteoblast-like cells. Nevertheless, the HA coating improved the cell interactions with the poly-Si surfaces based on the cell affinity to the specific chemical composition of the bone-like HA and/or to the higher HA roughness.

The (n,p) reaction as a probe of nuclear structure

International Nuclear Information System (INIS)

Jackson, K.P.; Celler, A.

1988-08-01

An account is given of some results of studies of the (n,p) reaction on nuclear targets at TRIUMF. The (n,p) reaction, inducing spin flip transitions in isospin space, appears to exhibit a unique sensitivity to certain aspects of nuclear structure. The TRIUMF facility is the first to exploit the (n,p) reaction as a detailed probe of nuclear structure at energies above 65 MeV. In the (n,p) reaction Fermi transitions are absent, but there is a dramatic impact on Gamow-Teller and other collective transactions. Some nuclear transition matrix elements can be estimated on the basis of (n,p) measurements. Experiments have been carried out at TRIUMF on Li 6 , Fe 5 4, and Zr 9 0 targets. The calibration of the (n,p) reaction as a probe of the Gamow-Teller strength B + GT has been achieved for three targets. (L.L.) (45 refs., 10 figs.)

Laser surface modification of polyethersulfone films: effect of laser wavelength on biocompatibility

International Nuclear Information System (INIS)

Pazokian, H; Jelvani, S; Mollabashi, M; Barzin, J

2013-01-01

In this paper laser ablation of polyethersulfone (PES) films regarding to the change in biocompatibility of the surface is investigated at 3 different wavelengths of 193nm (ArF), 248 nm (KrF) and 308 nm (XeCl). The optimum laser fluence and number of pulses for the improvement of the surface biocompatibility is found by examination of the surface behavior in contact with platelets and fibroblasts cells at 3 wavelengths. These biological modifications are explained by alteration of the surface morphology and chemistry following irradiation. The results show that the KrF laser is the best choice for treatment of PES in biological applications.

Direct measurement of surface-state conductance by microscopic four-point probe method

DEFF Research Database (Denmark)

Hasegawa, S.; Shiraki, I.; Tanikawa, T.

2002-01-01

For in situ measurements of local electrical conductivity of well defined crystal surfaces in ultrahigh vacuum, we have developed microscopic four-point probes with a probe spacing of several micrometres, installed in a scanning-electron - microscope/electron-diffraction chamber. The probe...... is precisely positioned on targeted areas of the sample surface by using piezoactuators. This apparatus enables conductivity measurement with extremely high surface sensitivity, resulting in direct access to surface-state conductivity of the surface superstructures, and clarifying the influence of atomic steps...

Competitive Reporter Monitored Amplification (CMA) - Quantification of Molecular Targets by Real Time Monitoring of Competitive Reporter Hybridization

Science.gov (United States)

Ullrich, Thomas; Ermantraut, Eugen; Schulz, Torsten; Steinmetzer, Katrin

2012-01-01

Background State of the art molecular diagnostic tests are based on the sensitive detection and quantification of nucleic acids. However, currently established diagnostic tests are characterized by elaborate and expensive technical solutions hindering the development of simple, affordable and compact point-of-care molecular tests. Methodology and Principal Findings The described competitive reporter monitored amplification allows the simultaneous amplification and quantification of multiple nucleic acid targets by polymerase chain reaction. Target quantification is accomplished by real-time detection of amplified nucleic acids utilizing a capture probe array and specific reporter probes. The reporter probes are fluorescently labeled oligonucleotides that are complementary to the respective capture probes on the array and to the respective sites of the target nucleic acids in solution. Capture probes and amplified target compete for reporter probes. Increasing amplicon concentration leads to decreased fluorescence signal at the respective capture probe position on the array which is measured after each cycle of amplification. In order to observe reporter probe hybridization in real-time without any additional washing steps, we have developed a mechanical fluorescence background displacement technique. Conclusions and Significance The system presented in this paper enables simultaneous detection and quantification of multiple targets. Moreover, the presented fluorescence background displacement technique provides a generic solution for real time monitoring of binding events of fluorescently labelled ligands to surface immobilized probes. With the model assay for the detection of human immunodeficiency virus type 1 and 2 (HIV 1/2), we have been able to observe the amplification kinetics of five targets simultaneously and accommodate two additional hybridization controls with a simple instrument set-up. The ability to accommodate multiple controls and targets into a

Competitive reporter monitored amplification (CMA--quantification of molecular targets by real time monitoring of competitive reporter hybridization.

Directory of Open Access Journals (Sweden)

Thomas Ullrich

Full Text Available BACKGROUND: State of the art molecular diagnostic tests are based on the sensitive detection and quantification of nucleic acids. However, currently established diagnostic tests are characterized by elaborate and expensive technical solutions hindering the development of simple, affordable and compact point-of-care molecular tests. METHODOLOGY AND PRINCIPAL FINDINGS: The described competitive reporter monitored amplification allows the simultaneous amplification and quantification of multiple nucleic acid targets by polymerase chain reaction. Target quantification is accomplished by real-time detection of amplified nucleic acids utilizing a capture probe array and specific reporter probes. The reporter probes are fluorescently labeled oligonucleotides that are complementary to the respective capture probes on the array and to the respective sites of the target nucleic acids in solution. Capture probes and amplified target compete for reporter probes. Increasing amplicon concentration leads to decreased fluorescence signal at the respective capture probe position on the array which is measured after each cycle of amplification. In order to observe reporter probe hybridization in real-time without any additional washing steps, we have developed a mechanical fluorescence background displacement technique. CONCLUSIONS AND SIGNIFICANCE: The system presented in this paper enables simultaneous detection and quantification of multiple targets. Moreover, the presented fluorescence background displacement technique provides a generic solution for real time monitoring of binding events of fluorescently labelled ligands to surface immobilized probes. With the model assay for the detection of human immunodeficiency virus type 1 and 2 (HIV 1/2, we have been able to observe the amplification kinetics of five targets simultaneously and accommodate two additional hybridization controls with a simple instrument set-up. The ability to accommodate multiple controls

Behaviour of a planar Langmuir probe in a laser ablation plasma

International Nuclear Information System (INIS)

Doggett, B.; Budtz-Joergensen, C.; Lunney, J.G.; Sheerin, P.; Turner, M.M.

2005-01-01

We have investigated some aspects of the behaviour of planar Langmuir probes in the supersonic plasma flow produced by laser ablation of solid materials in vacuum. The ablation was done using a 26 ns, 248 nm excimer laser, irradiating a silver target at 1 J cm -2 . We have compared the behaviour of the probe when it is orientated perpendicular and parallel to the plasma flow. In particular, we have shown that it is possible to adapt an analytical model, developed for plasma immersion ion implantation, to quantitatively describe the variation of the ion current with probe bias for the case when the plasma flow is along the probe surface. The electron temperature was also measured

Exploring the Hybridization Thermodynamics of Spherical Nucleic Acids to Tailor Probes for Diagnostic and Therapeutic Applications

Science.gov (United States)

Randeria, Pratik Shailesh

Spherical nucleic acids (SNAs), three-dimensional nanoparticle conjugates composed of densely packed and highly oriented oligonucleotides around organic or inorganic nanoparticles, are an emergent class of nanostructures that show promise as single-entity agents for intracellular messenger RNA (mRNA) detection and gene regulation. SNAs exhibit superior biocompatibility and biological properties compared to linear oligonucleotides, enabling them to overcome many of the limitations of linear oligonucleotides for use in biomedical applications. However, the origins of these biologically attractive properties are not well understood. In this dissertation, the chemistry underlying one such property is studied in detail, and the findings are applied towards the rational design of more effective SNAs for diagnostic and therapeutic applications. Chapter 1 introduces the synthesis of SNAs, the unique properties that make them superior to linear nucleic acids for biomedicine, and previously studied applications of these structures. Chapter 2 focuses on quantitatively studying the impact of the chemical structure of the SNA on its ability to hybridize multiple complementary nucleic acids. This chapter lays the groundwork for understanding the factors that govern SNA hybridization thermodynamics and how to tailor SNAs to increase their binding affinity to target mRNA strands. Chapters 3 and 4 capitalize on this knowledge to engineer probes for intracellular mRNA detection and gene regulation applications. Chapter 3 reports the development of an SNA-based probe that can simultaneously report the expression level of two different mRNA transcripts in live cells and differentiate diseased cells from non-diseased cells. Chapter 4 investigates the use of topically-applied SNAs to down-regulate a critical mediator of impaired wound healing in diabetic mice to accelerate wound closure. This study represents the first topical therapeutic application of SNA nanotechnology to treat open

Biocompatible electrospun polymer blends for biomedical applications.

Science.gov (United States)

Munj, Hrishikesh Ramesh; Nelson, M Tyler; Karandikar, Prathamesh Sadanand; Lannutti, John Joseph; Tomasko, David Lane

2014-10-01

Blends of natural and synthetic polymers have received considerable attention as biomaterials due to the potential to optimize both mechanical and bioactive properties. Electrospinning of biocompatible polymers is an efficient method producing biomimetic topographies suited to various applications. In the ultimate application, electrospun scaffolds must also incorporate drug/protein delivery for effective cell growth and tissue repair. This study explored the suitability of a ternary Polymethylmethacrylate-Polycaprolactone-gelatin blend in the preparation of electrospun scaffolds for biomedical applications. Tuning the blend composition allows control over scaffold mechanical properties and degradation rate. Significant improvements were observed in the mechanical properties of the blend compared with the individual components. In order to study drug delivery potential, triblends were impregnated with the model compound Rhodamine-B using sub/supercritical CO₂ infusion under benign conditions. Results show significantly distinct release profiles of the impregnated dye from the triblends. Specific factors such as porosity, degradation rate, stress relaxation, dye-polymer interactions, play key roles in impregnation and release. Each polymer component of the triblends shows distinct behavior during impregnation and release process. This affects the aforementioned factors and the release profiles of the dye. Careful control over blend composition and infusion conditions creates the flexibility needed to produce biocompatible electrospun scaffolds for a variety of biomedical applications. © 2014 Wiley Periodicals, Inc.

Comparison of in vitro biocompatibility of NanoBone(®) and BioOss(®) for human osteoblasts.

Science.gov (United States)

Liu, Qin; Douglas, Timothy; Zamponi, Christiane; Becker, Stephan T; Sherry, Eugene; Sivananthan, Sureshan; Warnke, Frauke; Wiltfang, Jörg; Warnke, Patrick H

2011-11-01

Scaffolds for bone tissue engineering seeded with the patient's own cells might be used as a preferable method to repair bone defects in the future. With the emerging new technologies of nanostructure design, new synthetic biomaterials are appearing on the market. Such scaffolds must be tested in vitro for their biocompatibility before clinical application. However, the choice between a natural or a synthetic biomaterial might be challenging for the doctor and the patient. In this study, we compared the biocompatibility of a synthetic bone substitute, NanoBone(®) , to the widely used natural bovine bone replacement material BioOss(®) . The in vitro behaviour of human osteoblasts on both materials was investigated. Cell performance was determined using scanning electron microscopy (SEM), cell vitality staining and four biocompatibility tests (LDH, MTT, WST, BrdU). We found that both materials showed low cytotoxicity and good biocompatibility. The MTT proliferation test was superior for Nanobone(®) . Both scaffolds caused only little damage to human osteoblasts and justify their clinical application. However, NanoBone(®) was able to support and promote proliferation of human osteoblasts slightly better than BioOss(®) in our chosen test set-up. The results may guide doctors and patients when being challenged with the choice between a natural or a synthetic biomaterial. Further experiments are necessary to determine the comparison of biocompatibility in vivo. © 2011 John Wiley & Sons A/S.

Immobilisation of a fibrillin-1 fragment enhances the biocompatibility of PTFE.

Science.gov (United States)

Hajian, Hamid; Wise, Steven G; Bax, Daniel V; Kondyurin, Alexey; Waterhouse, Anna; Dunn, Louise L; Kielty, Cay M; Yu, Young; Weiss, Anthony S; Bilek, Marcela M M; Bannon, Paul G; Ng, Martin K C

2014-04-01

Current vascular biomaterials exhibit poor biocompatibility characterised by failure to promote endothelialisation, predisposition to neoinitmal hyperplasia and excessive thrombogenicity. Fibrillin-1, a major constituent of microfibrils is associated with elastic fibres in the arterial wall. Fibrillin-1 binds to endothelial cells through an RGD cell adhesion motif in the fourth TB module. The RGD motif is present in PF8, a recombinant fibrillin-1 fragment. We investigated the potential of PF8 to improve the biocompatibility of PTFE. PF8 enhanced endothelial cell attachment and cell proliferation to a greater extent than fibronectin (pPTFE using plasma immersion ion implantation (PIII), retained these favourable cell interactive properties, again promoting endothelial cell attachment and proliferation. The thrombogenicity of covalently bound PF8 on PTFE was assessed in both static and dynamic conditions. In static conditions, uncoated PIII treated PTFE was more thrombogenic than untreated PTFE, while PF8 coating reduced thrombogenicity. Under flow, there was no difference in the thrombogenicity of PF8 coated PTFE and untreated PTFE. Immobilised PF8 shows a striking ability to promote attachment and growth of endothelial cells on PTFE, while providing a non-thrombogenic surface. These features make PF8 a promising candidate to improve the biocompatibility of current synthetic vascular grafts. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Novel probe for determining the size and position of a relativistic electron beam

International Nuclear Information System (INIS)

Orzechowski, T.J.; Koehler, H.; Edwards, W.; Nelson, M.; Marshall, B.

1984-01-01

In order to determine the size and position of a relativistic electron beam inside the wiggler magnetic field of a Free Electron Laser (FEL), we have developed a new probe which intercepts the electron beam on a high Z target and monitors the resulting bremsstrahlung radiation. The probe is designed to move along the entire three meters of the wiggler. This FEL is designed to operate in the microwave region (2 to 8 mm) and the interaction region is an oversized waveguide with a cross section 3 cm x 9.8 cm. The axial probe moves inside this waveguide. The probe stops the electron beam on a Tantalum target and the resulting x-rays are scattered in the forward direction. A scintillator behind the beam stop reacts to the x-rays and emits visible light in the region where the x-rays strike. An array of fiber optics behind the scintillator transmits the visible light to a Reticon camera system which images the visible pattern from the scintillator. Processing the optical image is done by digitizing and storing the image and/or recording the image on video tape. Resolution and performance of this probe will be discussed

Ad-hoc and context-dependent adjustments of selective attention in conflict control: an ERP study with visual probes.

Science.gov (United States)

Nigbur, R; Schneider, J; Sommer, W; Dimigen, O; Stürmer, B

2015-02-15

Cognitive conflict control in flanker tasks has often been described using the zoom-lens metaphor of selective attention. However, whether and how selective attention - in terms of suppression and enhancement - operates in this context has remained unclear. To examine the dynamic interplay of selective attention and cognitive control we used electrophysiological measures and presented task-irrelevant visual probe stimuli at foveal, parafoveal, and peripheral display positions. Target-flanker congruency varied either randomly from trial to trial (mixed-block) or block-wise (fixed-block) in order to induce reactive versus proactive control modes, respectively. Three EEG measures were used to capture ad-hoc adjustments within trials as well as effects of context-based predictions: the N1 component of the visual evoked potential (VEP) to probes, the VEP to targets, and the conflict-related midfrontal N2 component. Results from probe-VEPs indicate that enhanced processing of the foveal target rather than suppression of the peripheral flankers supports interference control. In incongruent mixed-block trials VEPs were larger to probes near the targets. In the fixed-blocks probe-VEPs were not modulated, but contrary to the mixed-block the preceding target-related VEP was affected by congruency. Results of the control-related N2 reveal largest amplitudes in the unpredictable context, which did not differentiate for stimulus and response incongruency. In contrast, in the predictable context, N2 amplitudes were reduced overall and differentiated between stimulus and response incongruency. Taken together these results imply that predictability alters interference control by a reconfiguration of stimulus processing. During unpredictable sequences participants adjust their attentional focus dynamically on a trial-by-trial basis as reflected in congruency-dependent probe-VEP-modulation. This reactive control mode also elicits larger N2 amplitudes. In contrast, when task demands

Two rhodamine lactam modulated lysosome-targetable fluorescence probes for sensitively and selectively monitoring subcellular organelle pH change

Energy Technology Data Exchange (ETDEWEB)

Li, Hongmei [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Wang, Cuiling [Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi' an 710069 (China); She, Mengyao; Zhu, Yuelu; Zhang, Jidong; Yang, Zheng [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Liu, Ping, E-mail: liuping@nwu.edu.cn [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Wang, Yaoyu [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Li, Jianli, E-mail: lijianli@nwu.edu.cn [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China)

2015-11-05

Be a powerful technique for convenient detection of pH change in living cells, especially at subcellular level, fluorescent probes has attracted more and more attention. In this work, we designed and synthesized three rhodamine lactam modulated fluorescent probes RS1, RS2 and RS3, which all respond sensitively toward weak acidity (pH range 4–6) via the photophysical property in buffer solution without interference from the other metal ions, and they also show ideal pKa values and excellent reversibility. Particularly, by changing the lone pair electrons distribution of lactam-N atom with different conjugations, RS2 and RS3 exhibit high quantum yield, negligible cytotoxicity and excellent permeability. They are suitable to stain selectively lysosomes of tumor cells and monitor its pH changes sensitively via optical molecular imaging. The above findings suggest that the probes we designed could act as ideal and easy method for investigating the pivotal role of H{sup +} in lysosomes and are potential pH detectors in disease diagnosis through direct intracellular imaging. - Highlights: • Two probes for sensitively and selectively monitoring weak acidic pH change. • The pKa of the probes was highly suitable for staining lysosomes in tumor cells. • The properties of those probes were changed by different conjugate system. • These probes have negligible cytotoxicity and good sensitivity in vivo.

Two rhodamine lactam modulated lysosome-targetable fluorescence probes for sensitively and selectively monitoring subcellular organelle pH change

International Nuclear Information System (INIS)

Li, Hongmei; Wang, Cuiling; She, Mengyao; Zhu, Yuelu; Zhang, Jidong; Yang, Zheng; Liu, Ping; Wang, Yaoyu; Li, Jianli

2015-01-01

Be a powerful technique for convenient detection of pH change in living cells, especially at subcellular level, fluorescent probes has attracted more and more attention. In this work, we designed and synthesized three rhodamine lactam modulated fluorescent probes RS1, RS2 and RS3, which all respond sensitively toward weak acidity (pH range 4–6) via the photophysical property in buffer solution without interference from the other metal ions, and they also show ideal pKa values and excellent reversibility. Particularly, by changing the lone pair electrons distribution of lactam-N atom with different conjugations, RS2 and RS3 exhibit high quantum yield, negligible cytotoxicity and excellent permeability. They are suitable to stain selectively lysosomes of tumor cells and monitor its pH changes sensitively via optical molecular imaging. The above findings suggest that the probes we designed could act as ideal and easy method for investigating the pivotal role of H + in lysosomes and are potential pH detectors in disease diagnosis through direct intracellular imaging. - Highlights: • Two probes for sensitively and selectively monitoring weak acidic pH change. • The pKa of the probes was highly suitable for staining lysosomes in tumor cells. • The properties of those probes were changed by different conjugate system. • These probes have negligible cytotoxicity and good sensitivity in vivo.

Fluorescence detection of natural RNA using rationally designed "clickable" oligonucleotide probes

DEFF Research Database (Denmark)

Okholm, Anders; Kjems, Jørgen; Astakhova, Kira

2014-01-01

Herein a reliable approach to the design of effective fluorescent probes for RNA detection is described. The fluorescence signalling of hybridization by internally positioned polyaromatic hydrocarbons and rhodamine dyes was achieved with a low fluorescence background signal, high fluorescence qua...... quantum yields at ambient and elevated temperature, high selectivity and signal specificity of the probes when binding to miR-7 and circRNA targets....

OligoRAP - an Oligo Re-Annotation Pipeline to improve annotation and estimate target specificity

NARCIS (Netherlands)

Neerincx, P.B.T.; Rauwerda, H.; Nie, H.; Groenen, M.A.M.; Breit, T.M.; Leunissen, J.A.M.

2009-01-01

Background: High throughput gene expression studies using oligonucleotide microarrays depend on the specificity of each oligonucleotide (oligo or probe) for its target gene. However, target specific probes can only be designed when a reference genome of the species at hand were completely sequenced,

Green chemistry approach for the synthesis of biocompatible graphene

Science.gov (United States)

Gurunathan, Sangiliyandi; Han, Jae Woong; Kim, Jin-Hoi

2013-01-01

Background Graphene is a single-atom thick, two-dimensional sheet of hexagonally arranged carbon atoms isolated from its three-dimensional parent material, graphite. One of the most common methods for preparation of graphene is chemical exfoliation of graphite using powerful oxidizing agents. Generally, graphene is synthesized through deoxygenation of graphene oxide (GO) by using hydrazine, which is one of the most widespread and strongest reducing agents. Due to the high toxicity of hydrazine, it is not a promising reducing agent in large-scale production of graphene; therefore, this study focused on a green or sustainable synthesis of graphene and the biocompatibility of graphene in primary mouse embryonic fibroblast cells (PMEFs). Methods Here, we demonstrated a simple, rapid, and green chemistry approach for the synthesis of reduced GO (rGO) from GO using triethylamine (TEA) as a reducing agent and stabilizing agent. The obtained TEA reduced GO (TEA-rGO) was characterized by ultraviolet (UV)–visible absorption spectroscopy, X-ray diffraction (XRD), particle size dynamic light scattering (DLS), scanning electron microscopy (SEM), Raman spectroscopy, and atomic force microscopy (AFM). Results The transition of graphene oxide to graphene was confirmed by UV–visible spectroscopy. XRD and SEM were used to investigate the crystallinity of graphene and the surface morphologies of prepared graphene respectively. The formation of defects further supports the functionalization of graphene as indicated in the Raman spectrum of TEA-rGO. Surface morphology and the thickness of the GO and TEA-rGO were analyzed using AFM. The presented results suggest that TEA-rGO shows significantly more biocompatibility with PMEFs cells than GO. Conclusion This is the first report about using TEA as a reducing as well as a stabilizing agent for the preparation of biocompatible graphene. The proposed safe and green method offers substitute routes for large-scale production of graphene

Corrosion resistance and biocompatibility of titanium surface coated with amorphous tantalum pentoxide

Energy Technology Data Exchange (ETDEWEB)

Sun, Ying-Sui [Department of Oral Biology, National Yang-Ming University, Taipei, Taiwan (China); Chang, Jean-Heng [Dental Department, Cheng Hsin General Hospital, Taipei, Taiwan (China); Huang, Her-Hsiung, E-mail: hhhuang@ym.edu.tw [Department of Dentistry, National Yang-Ming University, Taipei, Taiwan (China); Department of Dentistry, Taipei City Hospital, Taipei, Taiwan (China); Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan (China)

2013-01-01

Tantalum pentoxide (Ta{sub 2}O{sub 5}) possesses good corrosion resistance and biocompatibility. This study aimed to improve the corrosion resistance and biocompatibility of titanium (Ti) by coating it with an amorphous Ta{sub 2}O{sub 5} surface layer. An amorphous Ta{sub 2}O{sub 5} layer was prepared on the Ti surface using a simple hydrolysis–condensation process at room temperature. The surface characteristics of the test specimens were analyzed using X-ray photoelectron spectroscopy, glancing angle X-ray diffraction, field emission scanning electron microscopy, and contact angle measurements. The corrosion resistance of the test specimens was evaluated from the potentiodynamic polarization curves and ion release measurements in simulated blood plasma (SBP). The biocompatibility of the test specimens was evaluated in terms of the protein (albumin) adsorption, cell adhesion, and cell growth of human bone marrow mesenchymal stem cells (hBMSCs). The amorphous Ta{sub 2}O{sub 5} layer with a porous micro-/nano-scale topography, which was deposited on the Ti surface using a simple hydrolysis–condensation process, increased the corrosion resistance (i.e., increased the corrosion potential and decreased the anodic current and ion release) of the Ti in the SBP and improved the surface wettability, albumin adsorption, and cell adhesion. We conclude that the presence of an amorphous Ta{sub 2}O{sub 5} layer on the Ti surface increased the corrosion resistance and biocompatibility of Ti. - Highlights: ► Amorphous Ta{sub 2}O{sub 5} layer was coated on Ti using simple hydrolysis–condensation process. ► Ta{sub 2}O{sub 5} surface layer showed a micro-/nano-scale porous topography. ► Ta{sub 2}O{sub 5} layer enhanced wettability and corrosion resistance of Ti. ► Ta{sub 2}O{sub 5} layer enhanced protein adsorption, cell adhesion, and cell proliferation of Ti.

Harnessing what lies within: Programming immunity with biocompatible devices to treat human disease

Science.gov (United States)

Roberts, Reid Austin

Advances in our mechanistic insight of cellular function and how this relates to host physiology have revealed a world which is intimately connected at the macro and micro level. Our increasing understanding of biology exemplifies this, where cells respond to environmental cues through interconnected networks of proteins which function as receptors and adaptors to elicit gene expression changes that drive appropriate cellular programs for a given stimulus. Consequently, our deeper molecular appreciation of host homeostasis implicates aberrations of these pathways in nearly all major human disease categories, including those of infectious, metabolic, neurologic, oncogenic, and autoimmune etiology. We have come to recognize the mammalian immune system as a common network hub among all these varied pathologies. As such, the major goal of this dissertation is to identify a platform to program immune responses in mammals so that we may enhance our ability to treat disease and improve health in the 21st century. Using advances in materials science, in particular a recently developed particle fabrication technology termed Particle Replication in Non-wetting Templates (PRINT), our studies systematically assess the murine and human immune response to precisely fabricated nano- and microscale particles composed of biodegradable and biocompatible materials. We then build on these findings and present particle design parameters to program a number of clinically attractive immune responses by targeting endogenous cellular signaling pathways. These include control of particle uptake through surface modification, design parameters that modulate the magnitude and kinetics of biological signaling dynamics that can be used to exacerbate or dampen inflammatory responses, as well as particle designs which may be of use in treating allergies and autoimmune disorders. In total, this dissertation provides evidence that rational design of biocompatible nano- and microparticles is a viable

Metallic Zinc Exhibits Optimal Biocompatibility for Bioabsorbable Endovascular Stents

Science.gov (United States)

Bowen, Patrick K.; Guillory, Roger J.; Shearier, Emily R.; Seitz, Jan-Marten; Drelich, Jaroslaw; Bocks, Martin; Zhao, Feng; Goldman, Jeremy

2015-01-01

Although corrosion resistant bare metal stents are considered generally effective, their permanent presence in a diseased artery is an increasingly recognized limitation due to the potential for long-term complications. We previously reported that metallic zinc exhibited an ideal biocorrosion rate within murine aortas, thus raising the possibility of zinc as a candidate base material for endovascular stenting applications. This study was undertaken to further assess the arterial biocompatibility of metallic zinc. Metallic zinc wires were punctured and advanced into the rat abdominal aorta lumen for up to 6.5 months. This study demonstrated that metallic zinc did not provoke responses that often contribute to restenosis. Low cell densities and neointimal tissue thickness, along with tissue regeneration within the corroding implant, point to optimal biocompatibility of corroding zinc. Furthermore, the lack of progression in neointimal tissue thickness over 6.5 months or the presence of smooth muscle cells near the zinc implant suggest that the products of zinc corrosion may suppress the activities of inflammatory and smooth muscle cells. PMID:26249616

Long-term biocompatibility, chemistry, and function of microencapsulated pancreatic islets

NARCIS (Netherlands)

de Vos, P; van Hoogmoed, CG; van Zanten, J; Netter, S; Strubbe, JH; Busscher, HJ

Transplantation of encapsulated living cells is a promising approach for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by insufficient biocompatibility of the capsules. In the present study, we have implemented new as well as previously

Synthesis and detection of 3'-OH terminal biotin-labeled DNA probes

International Nuclear Information System (INIS)

Brakel, C.L.; Engelhardt, D.L.

1985-01-01

Nick translation has been used to prepare biotin-dUTP-containing DNA probes. These stable DNA probes have been identified, following hybridization to target DNA, by fluorescence using antibiotin antibodies or by enzyme reactions in which the enzyme has been linked to avidin or streptavidin. It is probable that this technology will be applicable to certain diagnostic determinations and that, with sufficient sensitivity, this technology might provide a system for obtaining rapid and specific diagnoses in situations presently requiring time-consuming growth assays. The sensitivity of this assay can be increased in two ways: (1) by increasing the amount of biotin contained in the DNA probes, and (2) by increasing the response to individual biotin molecules in the DNA probes. This report demonstrates that terminal deoxynucleotide transferase can be employed to increase the biotin content of DNA probes. We also introduce a new streptavidin-linked enzyme system that produces a greater response to biotinylated DNA probes than does streptavidin-linked horseradish peroxidase

Whole-cell hybridization of Methanosarcina cells with two new oligonucleotide probes

DEFF Research Database (Denmark)

Sørensen, A.H.; Torsvik, V.L.; Torsvik, T.

1997-01-01

Two new oligonucleotide probes targeting the 16S rRNA of the methanogenic genus Methanosarcina were developed. The probes have the following sequences (Escherichia coli numbering): probe SARCI551, 5'-GAC CCAATAATCACGATCAC-3', and probe SARCI645, 5'-TCCCGGTTCCAAGTCTGGC-3'. In situ hybridization...... with the fluorescently labelled probes required several modifications of standard procedures. Cells of Methanosarcina mazeii S-6 were found to lyse during the hybridization step if fixed in 3% formaldehyde and stored in 50% ethanol. Lysis was, however, not observed with cells fixed and stored in 1.6% formaldehyde-0.......85% NaCl. Extensive autofluorescence of the cells was found upon hybridization in the presence of 5 mM EDTA, but successful hybridization could be obtained without addition of this compound. The mounting agent Citifluor AF1, often used in conjugation with the fluorochrome fluorescein, was found to wash...

Nucleic acid hybridization assays employing dA-tailed capture probes. II. Advanced multiple capture methods

International Nuclear Information System (INIS)

Hunsaker, W.R.; Badri, H.; Lombardo, M.; Collins, M.L.

1989-01-01

A fourth capture is added to the reversible target capture procedure. This results in an improved radioisotopic detection limit of 7.3 x 10(-21) mol of target. In addition, the standard triple capture method is converted into a nonradioactive format with a detection limit of under 1 amol of target. The principal advantage of nonradioactive detection is that the entire assay can be performed in about 1 h. Nucleic acids are released from cells in the presence of the (capture probe) which contains a 3'-poly(dA) sequence and the (labeled probe) which contains a detectable nonradioactive moiety such as biotin. After a brief hybridization in solution, the target is captured on oligo(dT) magnetic particles. The target is further purified from sample impurities and excess labeled probe by recapture either once or twice more on fresh magnetic particles. The highly purified target is then concentrated to 200 nl by recapture onto a poly(dT) nitrocellulose filter and rapidly detected with streptavidin-alkaline phosphatase using bromochloroindolyl phosphate and nitroblue tetrazolium. Using this procedure, as little as 0.25 amol of a target plasmid has been detected nonradioactively in crude samples in just 1 h without prior purification of the DNA and RNA. Finally, a new procedure called background capture is introduced to complement the background-reducing power of RTC

Mobile Probing and Probes

DEFF Research Database (Denmark)

Duvaa, Uffe; Ørngreen, Rikke; Weinkouff Mathiasen, Anne-Gitte

2013-01-01

Mobile probing is a method, developed for learning about digital work situations, as an approach to discover new grounds. The method can be used when there is a need to know more about users and their work with certain tasks, but where users at the same time are distributed (in time and space......). Mobile probing was inspired by the cultural probe method, and was influenced by qualitative interview and inquiry approaches. The method has been used in two subsequent projects, involving school children (young adults at 15-17 years old) and employees (adults) in a consultancy company. Findings point...... to mobile probing being a flexible method for uncovering the unknowns, as a way of getting rich data to the analysis and design phases. On the other hand it is difficult to engage users to give in depth explanations, which seem easier in synchronous dialogs (whether online or face2face). The development...

Mobile Probing and Probes

DEFF Research Database (Denmark)

Duvaa, Uffe; Ørngreen, Rikke; Weinkouff, Anne-Gitte

2012-01-01

Mobile probing is a method, which has been developed for learning about digital work situations, as an approach to discover new grounds. The method can be used when there is a need to know more about users and their work with certain tasks, but where users at the same time are distributed (in time...... and space). Mobile probing was inspired by the cultural probe method, and was influenced by qualitative interview and inquiry approaches. The method has been used in two subsequent projects, involving school children (young adults at 15-17 years old) and employees (adults) in a consultancy company. Findings...... point to mobile probing being a flexible method for uncovering the unknowns, as a way of getting rich data to the analysis and design phases. On the other hand it is difficult to engage users to give in depth explanations, which seem easier in synchronous dialogs (whether online or face2face...

Synthesis of biocompatible AuAgS/Ag2S nanoclusters and their applications in photocatalysis and mercury detection

International Nuclear Information System (INIS)

Zhao, Qian; Chen, Shenna; Zhang, Lingyang; Huang, Haowen; Liu, Fengping; Liu, Xuanyong

2014-01-01

In this paper, a facile approach for preparation of AuAgS/Ag 2 S nanoclusters was developed. The unique AuAgS/Ag 2 S nanoclusters capped with biomolecules exhibit interesting excellent optical and catalytic properties. The fluorescent AuAgS/Ag 2 S nanoclusters show tunable luminescence depending on the nanocluster size. The apoptosis assay demonstrated that the AuAgS/Ag 2 S nanoclusters showed low cytotoxicity and good biocompatibility. Therefore, the nanoclusters can be used not only as a probe for labeling cells but also for their photocatalytic activity for photodegradation of organic dye. Moreover, a highly selective and sensitive assay for detection of mercury including Hg 2+ and undissociated mercury complexes was developed based on the quenching fluorescent AuAgS/Ag 2 S nanoclusters, which provides a promising approach for determining various forms of Hg in the mercury-based compounds in environment. These unique nanoclusters may have potential applications in biological labeling, sensing mercury, and photodegradation of various organic pollutants in waste water.Graphical Abstract

Biocompatibility study of protein capped and uncapped silver nanoparticles on human hemoglobin

Science.gov (United States)

Bhunia, Amit Kumar; Kanti Samanta, Pijus; Aich, Debasish; Saha, Satyajit; Kamilya, Tapanendu

2015-06-01

The interactions of human hemoglobin with protein capped silver nanoparticles and bare silver nanoparticles were studied to understand fundamental perspectives about the biocompatibility of protein capped silver nanoparticles compared with bare silver nanoparticles. Bare silver (Ag) nanoparticles (NPs) were prepared by the chemical reduction method. High resolution transmission electron microscopy (HRTEM) analysis along with absorption at ~390 nm indicated the formation of bare Ag NPs. Protein coated Ag NPs were prepared by a green synthesis method. Absorption at ~440 nm along with ~280 nm indicated the formation of protein coated Ag NPs. The biocompatibility of the above mentioned Ag NPs was studied by interaction with human hemoglobin (Hb) protein. In presence of bare Ag NPs, the Soret band of Hb was red shifted. This revealed the distortion of iron from the heme pockets of Hb. Also, the fluorescence peak of Hb was quenched and red shifted which indicated that Hb became unfolded in the presence of bare Ag NPs. No red shift of the absorption of Soret, along with no shift and quenching of the fluorescence peak of Hb were observed in the presence of protein coated Ag NPs. A hemolysis assay suggested that protein coated Ag NPs were more biocompatible than bare one.

Influence of Electropolishing and Magnetoelectropolishing on Corrosion and Biocompatibility of Titanium Implants

Science.gov (United States)

Rahman, Zia ur; Pompa, Luis; Haider, Waseem

2014-11-01

Titanium alloys are playing a vital role in the field of biomaterials due to their excellent corrosion resistance and biocompatibility. These alloys enhance the quality and longevity of human life by replacing or treating various parts of the body. However, as these materials are in constant contact with the aggressive body fluids, corrosion of these alloys leads to metal ions release. These ions leach to the adjacent tissues and result in adverse biological reactions and mechanical failure of implant. Surface modifications are used to improve corrosion resistance and biological activity without changing their bulk properties. In this investigation, electropolishing and magnetoelectropolishing were carried out on commercially pure titanium, Ti6Al4V, and Ti6Al4V-ELI. These surface modifications are known to effect surface charge, chemistry, morphology; wettability, corrosion resistance, and biocompatibility of these materials. In vitro cyclic potentiodynamic polarization tests were conducted in phosphate buffer saline in compliance with ASTM standard F-2129-12. The surface morphology, roughness, and wettability of these alloys were studied using scanning electron microscope, atomic force microscope, and contact angle meter, respectively. Moreover, biocompatibility of titanium alloys was assessed by growing MC3T3 pre-osteoblast cells on them.

Epithelial cell biocompatibility of silica nanospheres for contrast-enhanced ultrasound molecular imaging

Energy Technology Data Exchange (ETDEWEB)

Chiriaco, Fernanda; Conversano, Francesco; Soloperto, Giulia; Casciaro, Ernesto [Institute of Clinical Physiology, Bioengineering Division, National Research Council (Italy); Ragusa, Andrea [National Nanotechnology Laboratory of CNR-NANO (Italy); Sbenaglia, Enzo Antonio; Dipaola, Lucia [Institute of Clinical Physiology, Bioengineering Division, National Research Council (Italy); Casciaro, Sergio, E-mail: sergio.casciaro@cnr.it [Istituto di Fisiologia Clinica (CNR-IFC) c/o Campus Universitario Ecotekne, Consiglio Nazionale delle Ricerche (Italy)

2013-07-15

Nanosized particles are receiving increasing attention as future contrast agents (CAs) for ultrasound (US) molecular imaging, possibly decorated on its surface with biological recognition agents for targeted delivery and deposition of therapeutics. In particular, silica nanospheres (SiNSs) have been demonstrated to be feasible in terms of contrast enhancement on conventional US systems. In this work, we evaluated the cytotoxicity of SiNSs on breast cancer (MCF-7) and HeLa (cervical cancer) cells employing NSs with sizes ranging from 160 to 330 nm and concentration range of 1.5-5 mg/mL. Cell viability was evaluated in terms of size, dose and time dependence, performing the MTT reduction assay with coated and uncoated SiNSs. Whereas uncoated SiNSs caused a variable significant decrease in cell viability on both cell lines mainly depending on size and exposure time, PEGylated SiNSs (SiNSs-PEG) exhibit a high level of biocompatibility. In fact, after 72-h incubation, viability of both cell types was above the cutoff value of 70 % at concentration up to 5 mg/mL. We also investigated the acoustical behavior of coated and uncoated SiNSs within conventional diagnostic US fields in order to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable CAs. Our results indicate that the employment of SiNSs with diameters around 240 nm assures the most effective contrast enhancement even at the lowest tested concentration, coupled with the possibility of targeting all tumor tissues, being the SiNSs still in a size range where reticuloendothelial system trapping effect is relatively low.

Epithelial cell biocompatibility of silica nanospheres for contrast-enhanced ultrasound molecular imaging

International Nuclear Information System (INIS)

Chiriacò, Fernanda; Conversano, Francesco; Soloperto, Giulia; Casciaro, Ernesto; Ragusa, Andrea; Sbenaglia, Enzo Antonio; Dipaola, Lucia; Casciaro, Sergio

2013-01-01

Nanosized particles are receiving increasing attention as future contrast agents (CAs) for ultrasound (US) molecular imaging, possibly decorated on its surface with biological recognition agents for targeted delivery and deposition of therapeutics. In particular, silica nanospheres (SiNSs) have been demonstrated to be feasible in terms of contrast enhancement on conventional US systems. In this work, we evaluated the cytotoxicity of SiNSs on breast cancer (MCF-7) and HeLa (cervical cancer) cells employing NSs with sizes ranging from 160 to 330 nm and concentration range of 1.5–5 mg/mL. Cell viability was evaluated in terms of size, dose and time dependence, performing the MTT reduction assay with coated and uncoated SiNSs. Whereas uncoated SiNSs caused a variable significant decrease in cell viability on both cell lines mainly depending on size and exposure time, PEGylated SiNSs (SiNSs-PEG) exhibit a high level of biocompatibility. In fact, after 72-h incubation, viability of both cell types was above the cutoff value of 70 % at concentration up to 5 mg/mL. We also investigated the acoustical behavior of coated and uncoated SiNSs within conventional diagnostic US fields in order to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable CAs. Our results indicate that the employment of SiNSs with diameters around 240 nm assures the most effective contrast enhancement even at the lowest tested concentration, coupled with the possibility of targeting all tumor tissues, being the SiNSs still in a size range where reticuloendothelial system trapping effect is relatively low

Biodegradable magnesium alloys for orthopaedic applications: A review on corrosion, biocompatibility and surface modifications

Energy Technology Data Exchange (ETDEWEB)

Agarwal, Sankalp [Centre for Research in Engineering and Surface Technology, FOCAS Institute, Dublin Institute of Technology (Ireland); School of Food Science and Environmental Health, Cathal Brugha Street, Dublin Institute of Technology (Ireland); Curtin, James [School of Food Science and Environmental Health, Cathal Brugha Street, Dublin Institute of Technology (Ireland); Duffy, Brendan [Centre for Research in Engineering and Surface Technology, FOCAS Institute, Dublin Institute of Technology (Ireland); Jaiswal, Swarna, E-mail: swarna.jaiswal@dit.ie [Centre for Research in Engineering and Surface Technology, FOCAS Institute, Dublin Institute of Technology (Ireland)

2016-11-01

Magnesium (Mg) and its alloys have been extensively explored as potential biodegradable implant materials for orthopaedic applications (e.g. Fracture fixation). However, the rapid corrosion of Mg based alloys in physiological conditions has delayed their introduction for therapeutic applications to date. The present review focuses on corrosion, biocompatibility and surface modifications of biodegradable Mg alloys for orthopaedic applications. Initially, the corrosion behaviour of Mg alloys and the effect of alloying elements on corrosion and biocompatibility is discussed. Furthermore, the influence of polymeric deposit coatings, namely sol-gel, synthetic aliphatic polyesters and natural polymers on corrosion and biological performance of Mg and its alloy for orthopaedic applications are presented. It was found that inclusion of alloying elements such as Al, Mn, Ca, Zn and rare earth elements provides improved corrosion resistance to Mg alloys. It has been also observed that sol-gel and synthetic aliphatic polyesters based coatings exhibit improved corrosion resistance as compared to natural polymers, which has higher biocompatibility due to their biomimetic nature. It is concluded that, surface modification is a promising approach to improve the performance of Mg-based biomaterials for orthopaedic applications. - Highlights: • The Mg based alloys are promising candidates for orthopaedic applications. • The rapid corrosion of Mg can affect human cells, and causes infection and implant failure. • The various physiological factors and Mg alloying elements affect the corrosion and mechanical properties of implants. • The polymeric deposit coatings enhance the corrosion resistance and biocompatibility.

Biodegradable magnesium alloys for orthopaedic applications: A review on corrosion, biocompatibility and surface modifications

International Nuclear Information System (INIS)

Agarwal, Sankalp; Curtin, James; Duffy, Brendan; Jaiswal, Swarna

2016-01-01

Magnesium (Mg) and its alloys have been extensively explored as potential biodegradable implant materials for orthopaedic applications (e.g. Fracture fixation). However, the rapid corrosion of Mg based alloys in physiological conditions has delayed their introduction for therapeutic applications to date. The present review focuses on corrosion, biocompatibility and surface modifications of biodegradable Mg alloys for orthopaedic applications. Initially, the corrosion behaviour of Mg alloys and the effect of alloying elements on corrosion and biocompatibility is discussed. Furthermore, the influence of polymeric deposit coatings, namely sol-gel, synthetic aliphatic polyesters and natural polymers on corrosion and biological performance of Mg and its alloy for orthopaedic applications are presented. It was found that inclusion of alloying elements such as Al, Mn, Ca, Zn and rare earth elements provides improved corrosion resistance to Mg alloys. It has been also observed that sol-gel and synthetic aliphatic polyesters based coatings exhibit improved corrosion resistance as compared to natural polymers, which has higher biocompatibility due to their biomimetic nature. It is concluded that, surface modification is a promising approach to improve the performance of Mg-based biomaterials for orthopaedic applications. - Highlights: • The Mg based alloys are promising candidates for orthopaedic applications. • The rapid corrosion of Mg can affect human cells, and causes infection and implant failure. • The various physiological factors and Mg alloying elements affect the corrosion and mechanical properties of implants. • The polymeric deposit coatings enhance the corrosion resistance and biocompatibility.

Synthesis of biocompatible surfaces by nanotechnology methods

OpenAIRE

Alekhin , A. ,; Boleiko , G. ,; Gudkova , S. ,; Markeev , A. ,; Sigarev , A. ,; Toknova , V. ,; Kirilenko , A. ,; Lapshin , R. ,; Kozlov , E. ,; Tetyukhin , D. ,

2010-01-01

International audience; The modification of the surface of low-density polyethylene (LDPE) and polyurethane (PU) by means of the pulsed ion-plasma deposition of nanostructural carbon coatings at 20–60°C has been studied. The effect of this low-temperature treatment on the biocompatibility of the LDPE and PU has been assessed. Optimum technological parameters for the formation of mosaic carbon nanostructures with a thickness of 0.3–15 nm and a cluster lateral size of 10–500 nm are determined. ...

Development of Bioorthogonal Reactions and Their Applications in Bioconjugation

Directory of Open Access Journals (Sweden)

Mengmeng Zheng

2015-02-01

Full Text Available Biomolecule labeling using chemical probes with specific biological activities has played important roles for the elucidation of complicated biological processes. Selective bioconjugation strategies are highly-demanded in the construction of various small-molecule probes to explore complex biological systems. Bioorthogonal reactions that undergo fast and selective ligation under bio-compatible conditions have found diverse applications in the development of new bioconjugation strategies. The development of new bioorthogonal reactions in the past decade has been summarized with comments on their potentials as bioconjugation method in the construction of various biological probes for investigating their target biomolecules. For the applications of bioorthogonal reactions in the site-selective biomolecule conjugation, examples have been presented on the bioconjugation of protein, glycan, nucleic acids and lipids.

High affinity γPNA sandwich hybridization assay for rapid detection of short nucleic acid targets with single mismatch discrimination.

Science.gov (United States)

Goldman, Johnathan M; Zhang, Li Ang; Manna, Arunava; Armitage, Bruce A; Ly, Danith H; Schneider, James W

2013-07-08

Hybridization analysis of short DNA and RNA targets presents many challenges for detection. The commonly employed sandwich hybridization approach cannot be implemented for these short targets due to insufficient probe-target binding strengths for unmodified DNA probes. Here, we present a method capable of rapid and stable sandwich hybridization detection for 22 nucleotide DNA and RNA targets. Stable hybridization is achieved using an n-alkylated, polyethylene glycol γ-carbon modified peptide nucleic acid (γPNA) amphiphile. The γPNA's exceptionally high affinity enables stable hybridization of a second DNA-based probe to the remaining bases of the short target. Upon hybridization of both probes, an electrophoretic mobility shift is measured via interaction of the n-alkane modification on the γPNA with capillary electrophoresis running buffer containing nonionic surfactant micelles. We find that sandwich hybridization of both probes is stable under multiple binding configurations and demonstrate single base mismatch discrimination. The binding strength of both probes is also stabilized via coaxial stacking on adjacent hybridization to targets. We conclude with a discussion on the implementation of the proposed sandwich hybridization assay as a high-throughput microRNA detection method.

Accurate multi-robot targeting for keyhole neurosurgery based on external sensor monitoring.

Science.gov (United States)

Comparetti, Mirko Daniele; Vaccarella, Alberto; Dyagilev, Ilya; Shoham, Moshe; Ferrigno, Giancarlo; De Momi, Elena

2012-05-01

Robotics has recently been introduced in surgery to improve intervention accuracy, to reduce invasiveness and to allow new surgical procedures. In this framework, the ROBOCAST system is an optically surveyed multi-robot chain aimed at enhancing the accuracy of surgical probe insertion during keyhole neurosurgery procedures. The system encompasses three robots, connected as a multiple kinematic chain (serial and parallel), totalling 13 degrees of freedom, and it is used to automatically align the probe onto a desired planned trajectory. The probe is then inserted in the brain, towards the planned target, by means of a haptic interface. This paper presents a new iterative targeting approach to be used in surgical robotic navigation, where the multi-robot chain is used to align the surgical probe to the planned pose, and an external sensor is used to decrease the alignment errors. The iterative targeting was tested in an operating room environment using a skull phantom, and the targets were selected on magnetic resonance images. The proposed targeting procedure allows about 0.3 mm to be obtained as the residual median Euclidean distance between the planned and the desired targets, thus satisfying the surgical accuracy requirements (1 mm), due to the resolution of the diffused medical images. The performances proved to be independent of the robot optical sensor calibration accuracy.

Biocompatibility of Poly(ester amide (PEA Microfibrils in Ocular Tissues

Directory of Open Access Journals (Sweden)

Martina Kropp

2014-01-01

Full Text Available Drug delivery systems (DDS are able to deliver, over long periods of time, therapeutic concentrations of drugs requiring frequent administration. Two classes of DDS are available, biodegradable and non-biodegradable. The larger non-biodegradable implants ensure long-term delivery, but require surgical interventions. Biodegradable biomaterials are smaller, injectable implants, but degrade hydrolytically and release drugs in non-zero order kinetics, which is inefficient for long-term sustained drug release. Biodegradable poly(ester amides (PEAs may overcome these difficulties. To assess their ocular biocompatibility and long-term behavior, PEA fibrils were analyzed in vitro and in vivo. In vitro, incubation in vitreous humor changes to PEA structure, suggests degradation by surface erosion, enabling drug release with zero order kinetics. Clinical and histological analysis of PEA fibrils implanted subconjunctivally and intravitreally showed the absence of an inflammatory response or other pathological tissue alteration. This study shows that PEA fibrils are biocompatible with ocular environment and degrade by surface erosion.

Shape memory alloys: metallurgy, biocompatibility, and biomechanics for neurosurgical applications.

Science.gov (United States)

Hoh, Daniel J; Hoh, Brian L; Amar, Arun P; Wang, Michael Y

2009-05-01

SHAPE MEMORY ALLOYS possess distinct dynamic properties with particular applications in neurosurgery. Because of their unique physical characteristics, these materials are finding increasing application where resiliency, conformation, and actuation are needed. Nitinol, the most frequently manufactured shape memory alloy, responds to thermal and mechanical stimuli with remarkable mechanical properties such as shape memory effect, super-elasticity, and high damping capacity. Nitinol has found particular use in the biomedical community because of its excellent fatigue resistance and biocompatibility, with special interest in neurosurgical applications. The properties of nitinol and its diffusionless phase transformations contribute to these unique mechanical capabilities. The features of nitinol, particularly its shape memory effect, super-elasticity, damping capacity, as well as its biocompatibility and biomechanics are discussed herein. Current and future applications of nitinol and other shape memory alloys in endovascular, spinal, and minimally invasive neurosurgery are introduced. An understanding of the metallurgic properties of nitinol provides a foundation for further exploration of its use in neurosurgical implant design.

Development of specific oligonucleotide probes for the identification and in situ detection of hydrocarbon-degrading Alcanivorax strains.

Science.gov (United States)

Syutsubo, K; Kishira, H; Harayama, S

2001-06-01

The genus Alcanivorax comprises diverse hydrocarbon-degrading marine bacteria. Novel 16S rRNA-targeted oligonucleotide DNA probes (ALV735 and ALV735-b) were developed to quantify two subgroups of the Alcanivorax/Fundibacter group by fluorescence in situ hybridization (FISH), and the conditions for the single-mismatch discrimination of the probes were optimized. The specificity of the probes was improved further using a singly mismatched oligonucleotide as a competitor. The growth of Alcanivorax cells in crude oil-contaminated sea water under the biostimulation condition was investigated by FISH with the probe ALV735, which targeted the main cluster of the Alcanivorax/Fundibacter group. The size of the Alcanivorax population increased with increasing incubation time and accounted for 91% of the 4',6-diamidino-2-phenylindole (DAPI) count after incubation for 2 weeks. The probes developed in this study are useful for detecting Alcanivorax populations in petroleum hydrocarbon-degrading microbial consortia.

SERS microscopy: plasmonic nanoparticle probes and biomedical applications

Science.gov (United States)

Gellner, M.; Schütz, M.; Salehi, M.; Packeisen, J.; Ströbel, P.; Marx, A.; Schmuck, C.; Schlücker, S.

2010-08-01

Nanoparticle probes for use in targeted detection schemes and readout by surface-enhanced Raman scattering (SERS) comprise a metal core, Raman reporter molecules and a protective shell. One design of SERS labels specifically optimized for biomedical applications in conjunction with red laser excitation is based on tunable gold/silver nanoshells, which are completely covered by a self-assembled monolayer (SAM) of Raman reporters. A shell around the SAM-coated metal core stabilizes the colloid and prevents particle aggregation. The optical properties and SERS efficiencies of these plasmonic nanostructures are characterized both experimentally and theoretically. Subsequent bioconjugation of SERS probes to ligands such as antibodies is a prerequisite for the selective detection of the corresponding target molecule via the characteristic Raman signature of the label. Biomedical imaging applications of SERS-labeled antibodies for tumor diagnostics by SERS microscopy are presented, using the localization of the tumor suppressor p63 in prostate tissue sections as an example.

Biocompatibility evaluations and biomedical sensing applications of nitric oxide-releasing/generating polymeric materials

Science.gov (United States)

Wu, Yiduo

Nitric oxide (NO) is a potent signaling molecule secreted by healthy vascular endothelial cells (EC) that is capable of inhibiting the activation and adhesion of platelets, preventing inflammation and inducing vasodilation. Polymeric materials that mimic the EC through the continuous release or generation of NO are expected to exhibit enhanced biocompatibility in vivo. In this dissertation research, the biocompatibility of novel NO-releasing/generating materials has been evaluated via both in vitro and in vivo studies. A new in vitro platelet adhesion assay has been designed to quantify platelet adhesion on NO-releasing/generating polymer surfaces via their innate lactate dehydrogenase (LDH) content. Using this assay, it was discovered that continuous NO fluxes of up to 7.05 x10-10 mol cm-2 min-1 emitted from the polymer surfaces could reduce platelet adhesion by almost 80%. Such an in vitro biocompatibility assay can be employed as a preliminary screening method in the development of new NO-releasing/generating materials. In addition, the first in vivo biocompatibility evaluation of NO-generating polymers was conducted in a porcine artery model for intravascular oxygen sensing catheters. The Cu(I)-catalyzed decomposition of endogenous S-nitrosothiols (RSNOs) generated NO in situ at the polymer/blood interface and offered enhanced biocompatibility to the NO-generating catheters along with more accurate analytical results for intra-arterial measurements of PO2 levels. NO-generating polymers can also be utilized to fabricate electrochemical RSNO sensors based on the amperometric detection of NO generated by the reaction of RSNOs with immobilized catalysts. Unlike conventional methodologies employed to measure labile RSNO, the advantage of the RSNO sensor method is that measurement in whole blood samples is possible and this minimizes sample processing artifacts in RSNO measurements. An electrochemical RSNO sensor with organoselenium crosslinked polyethylenimine (RSe

Investigation into Effects of Scanning Speed on in Vitro Biocompatibility of Selective Laser Melted 316L Stainless Steel Parts

Directory of Open Access Journals (Sweden)

Shang Yitong

2017-01-01

Full Text Available In recent years, selective laser melting (SLM has gained an important place in fabrication due to their strong individualization which cannot be manufactured using conventional processes such as casting or forging. By proper control of the SLM processing parameters, characteristics of the alloy can be optimized. In the present work, 316L stainless steel (SS, as a widely used biomedical material, is investigated in terms of the effects of scanning speed on in vitro biocompatibility during SLM process. Cytotoxicity assay is adopted to assess the in vitro biocompatibility. The results show the scanning speed strongly affects the in vitro biocompatibility of 316L SS parts and with prolongs of incubation time, the cytotoxicity increase and the in vitro biocompatibility gets worse. The optimal parameters are determined as follows: scanning speed of 900 mm/s, laser power of 195 W, hatch spacing of 0.09 mm and layer thickness of 0.02 mm. The processing parameters lead to the change of surface morphology and microstructures of samples, which can affect the amount of toxic ions release, such as Cr, Mo and Co, that can increase risks to patient health and reduce the biocompatibility.

Tribological properties, corrosion resistance and biocompatibility of magnetron sputtered titanium-amorphous carbon coatings

International Nuclear Information System (INIS)

Dhandapani, Vishnu Shankar; Subbiah, Ramesh; Thangavel, Elangovan; Arumugam, Madhankumar; Park, Kwideok; Gasem, Zuhair M.; Veeraragavan, Veeravazhuthi; Kim, Dae-Eun

2016-01-01

Highlights: • a-C:Ti nanocomposite coatings were prepared on 316L stainless steel by using R.F. magnetron sputtering method. • Properties of the nanocomposite coatings were analyzed with respect to titanium content. • Corrosion resistance, biocompatibility and hydrophobicity of nanocomposite coating were enhanced with increasing titanium content. • Coating with 2.33 at.% titanium showed superior tribological properties compared to other coatings. - Abstract: Amorphous carbon incorporated with titanium (a-C:Ti) was coated on 316L stainless steel (SS) by magnetron sputtering technique to attain superior tribological properties, corrosion resistance and biocompatibility. The morphology, topography and functional groups of the nanostructured a-C:Ti coatings in various concentrations were analyzed using atomic force microscopy (AFM), Raman, X-Ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). Raman and XPS analyses confirmed the increase in sp"2 bonds with increasing titanium content in the a-C matrix. TEM analysis confirmed the composite nature of the coating and the presence of nanostructured TiC for Ti content of 2.33 at.%. This coating showed superior tribological properties compared to the other a-C:Ti coatings. Furthermore, electrochemical corrosion studies were performed against stimulated body fluid medium in which all the a-C:Ti coatings showed improved corrosion resistance than the pure a-C coating. Preosteoblasts proliferation and viability on the specimens were tested and the results showed that a-C:Ti coatings with relatively high Ti (3.77 at.%) content had better biocompatibility. Based on the results of this work, highly durable coatings with good biocompatibility could be achieved by incorporation of optimum amount of Ti in a-C coatings deposited on SS by magnetron sputtering technique.

Triple probe interrogation of spokes in a HiPIMS discharge

International Nuclear Information System (INIS)

Lockwood Estrin, F; Bradley, J W; Karkari, S K

2017-01-01

Using a triple probe situated above the racetrack and inside the magnetic trap of a magnetron, rotating spoke-like structures have been clearly identified in a single HiPIMS pulse as periodic modulations of the electron temperature T e , electron density n e , ion saturation current I isat , floating potential V f and plasma potential V p . The spokes rotate in the E   ×   B direction with a velocity of ∼8.8 km s −1 . Defining the spoke shape from the footprint of the ion current, they deliver to flush-mounted probes embedded in the target, each spoke can be characterised by a dense but cool leading edge ( n e ∼ 2.0  ×  10 19 m −3 , T e ∼ 2.1 eV) and a relatively hotter but more rarefied trailing edge ( n e ∼ 1  ×  10 19 m −3 , T e ∼ 3.9 eV). Measurements of V p show a potential hump towards the rear of the spoke, separated from regions of the highest density, with plasma potentials up to 8 V more positive than the inter-spoke regions. Azimuthal electric fields of ∼1 kV m −1 associated with these structures are calculated. Transforming the triple probe time-traces to functions of the azimuthal angle θ and assuming a Gaussian radial profile for the plasma parameters, 2D spatial maps of n e , T e and V p have been constructed as well as the target ion current density J p from the embedded probes. The phase relationship between T e , V p and n e can be clearly seen using this representation with n e leading T e and V p with a phase shift between them of ∼50°. Regions of maximum ion current to the target, delivered by individual spokes, coincide with the overlap of regions of high n e and T e measured above the target at a height of 15 mm. Ions created at elevated positions above the target in the observed dense region will take several micro-seconds to reach that surface, so contributing to the target ion current in the following spokes. (paper)

Polyelectrolyte-coated nanocapsules containing undecylenic acid: Synthesis, biocompatibility and neuroprotective properties.

Science.gov (United States)

Piotrowski, Marek; Jantas, Danuta; Szczepanowicz, Krzysztof; Łukasiewicz, Sylwia; Lasoń, Władysław; Warszyński, Piotr

2015-11-01

The main objectives of the present study were to investigate the biocompatibility of polyelectrolyte-coated nanocapsules and to evaluate the neuroprotective action of the nanoencapsulated water-insoluble neuroprotective drug-undecylenic acid (UDA), in vitro. Core-shell nanocapsules were synthesized using nanoemulsification and the layer-by-layer (LbL) technique (by saturation method). The average size of synthesized nanocapsules was around 80 nm and the concentration was 2.5 × 10(10) particles/ml. Their zeta potential values ranged from less than -30 mV for the ones with external polyanion layers through -4 mV for the PEG-ylated layers to more than 30 mV for the polycation layers. Biocompatibility of synthesized nanocarriers was evaluated in the SH-SY5Y human neuroblastoma cell line using cell viability/toxicity assays (MTT reduction, LDH release). The results obtained showed that synthesized nanocapsules coated with PLL and PGA (also PEG-ylated) were non-toxic to SH-SY5Y cells, therefore, they were used as nanocarriers for UDA. Moreover, studies with ROD/FITC-labeled polyelectrolytes demonstrated approximately 20% cellular uptake of synthetized nanocapsules. Further studies showed that nanoencapsulated form of UDA was biocompatible and protected SH-SY5Y cells against the staurosporine-induced damage in lower concentrations than those of the same drug added directly to the culture medium. These data suggest that designed nanocapsules might serve as novel, promising delivery systems for neuroprotective agents. Copyright © 2015 Elsevier B.V. All rights reserved.

OligoRAP – an Oligo Re-Annotation Pipeline to improve annotation and estimate target specificity

NARCIS (Netherlands)

Neerincx, P.; Rauwerda, H.; Nie, H.; Groenen, M.A.M.; Breit, T.M.; Leunissen, J.A.M.

2009-01-01

Background - High throughput gene expression studies using oligonucleotide microarrays depend on the specificity of each oligonucleotide (oligo or probe) for its target gene. However, target specific probes can only be designed when a reference genome of the species at hand were completely

Small molecule probes for cellular death machines.

Science.gov (United States)

Li, Ying; Qian, Lihui; Yuan, Junying

2017-08-01

The past decade has witnessed a significant expansion of our understanding about the regulated cell death mechanisms beyond apoptosis. The application of chemical biological approaches had played a major role in driving these exciting discoveries. The discovery and use of small molecule probes in cell death research has not only revealed significant insights into the regulatory mechanism of cell death but also provided new drug targets and lead drug candidates for developing therapeutics of human diseases with huge unmet need. Here, we provide an overview of small molecule modulators for necroptosis and ferroptosis, two non-apoptotic cell death mechanisms, and discuss the molecular pathways and relevant pathophysiological mechanisms revealed by the judicial applications of such small molecule probes. We suggest that the development and applications of small molecule probes for non-apoptotic cell death mechanisms provide an outstanding example showcasing the power of chemical biology in exploring novel biological mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aptamer Recognition Induced Target-Bridged Strategy for Proteins Detection Based on Magnetic Chitosan and Silver/Chitosan Nanoparticles Using Surface-Enhanced Raman Spectroscopy.

Science.gov (United States)

He, Jincan; Li, Gongke; Hu, Yuling

2015-11-03

Poor selectivity and biocompability remain problems in applying surface-enhanced Raman spectroscopy (SERS) for direct detection of proteins due to similar spectra of most proteins and overlapping Raman bands in complex mixtures. To solve these problems, an aptamer recognition induced target-bridged strategy based on magnetic chitosan (MCS) and silver/chitosan nanoparticles (Ag@CS NPs) using SERS was developed for detection of protein benefiting from specific affinity of aptamers and biocompatibility of chitosan (CS). In this process, one aptamer (or antibody) modified MCS worked as capture probes through the affinity binding site of protein. The other aptamer modified Raman report molecules encapsulated Ag@CS NPs were used as SERS sensing probes based on the other binding site of protein. The sandwich complexes of aptamer (antibody)/protein/aptamer were separated easily with a magnet from biological samples, and the concentration of protein was indirectly reflected by the intensity variation of SERS signal of Raman report molecules. To explore the universality of the strategy, three different kinds of proteins including thrombin, platelet derived growth factor BB (PDGF BB) and immunoglobulin E (lgE) were investigated. The major advantages of this aptamer recognition induced target-bridged strategy are convenient operation with a magnet, stable signal expressing resulting from preventing loss of report molecules with the help of CS shell, and the avoidance of slow diffusion-limited kinetics problems occurring on a solid substrate. To demonstrate the feasibility of the proposed strategy, the method was applied to detection of PDGF BB in clinical samples. The limit of detection (LOD) of PDGF BB was estimated to be 3.2 pg/mL. The results obtained from human serum of healthy persons and cancer patients using the proposed strategy showed good agreement with that of the ELISA method but with wider linear range, more convenient operation, and lower cost. The proposed

Sub-micron opto-chemical probes for studying living neurons

Science.gov (United States)

Hossein-Zadeh, M.; Delgado, J.; Schweizer, F.; Lieberman, R.

2017-02-01

We have fabricated sub-micron opto-chemical probes for pH, oxygen and calcium monitoring and demonstrated their application in intracellular and extracellular monitoring of neurons (cortical neuronal cultures and acute hippocampal slices). Using these probes, we have measured extracellular pH in the stratum radiatum of the CA1 region of mouse hippocampus upon stimulation of presynaptic Schaffer collateral axons. Synaptic transmission was monitored using standard electrophysiological techniques. We find that the local pH transiently changes in response to synaptic stimulation. In addition, the geometry of the functionalized region on the probe combined with high sensitivity imaging enables simultaneous monitoring of spatially adjacent but distinct compartments. As proof of concept we impaled cultured neurons with the probe measured calcium and pH inside as well as directly outside of neurons as we changed the pH and calcium concentration in the physiological solution in the perfusion chamber. As such these probes can be used to study the impact of the environment on both cellular and extra-cellular space. Additionally as the chemical properties of the surrounding medium can be controlled and monitored with high precision, these probes enable differential measurement of the target parameter referenced to a stable bath. This approach eliminates the uncertainties associated with non-chemical fluctuations in the fluorescent emission and result in a self-calibrated opto-chemical probe. We have also demonstrated multifunctional probes that are capable of measuring up to three parameters in the extracellular space in brain slices.

Biocompatibility of orthopaedic implants on bone forming cells

OpenAIRE

Kapanen, A. (Anita)

2002-01-01

Abstract Reindeer antler was studied for its possible use as a bone implant material. A molecular biological study showed that antler contains a growth factor promoting bone formation. Ectopic bone formation assay showed that antler is not an equally effective inducer as allogenic material. Ectopic bone formation assay was optimised for biocompatibility studies of orthopaedic NiTi implants. Ti-6Al-4V and stainless steel were used as reference materials. The assay...

A bispecific peptide based near-infrared probe for in vivo tumor diagnosis

Science.gov (United States)

Ding, Li; Chen, Wei R.; Gu, Yueqing

2013-02-01

The epidermal growth factor receptor EGFR and HER2 are members of recepeter tyrosine kinase family. Overexpression of EGFR and HER2 has been observed in a variety of human tumors, making these receptors promising targets for tumor diagnosis. An affibody targeting HER2 and a nanobody targeting EGFR were reported before. In this Manuscript, we described an bispecific peptide combined with an affibody and a nanonbody through a linker―（G4S）3 . And the bispecific peptide was labeled with near-infrared (NIR) fluorochrome ICG-Der-02 for in vivo tumor EGFR and HER2 targeting. Afterwards, the EGFR and HER2 specificity of the fluorescent probe was tested in vitro for receptor binding assay and fluorescence microscopy and in vivo for subcutaneous MDA-MB-231 tumor targeting. The results indicated that the bispecific peptide had a high affinity to EGFR and HER2. Besides, in vitro and in vivo tumor targeting experiment indicated that the ICG-Der-02-( bispecific peptide) showed excellent tumor activity accumulation. Noninvasive NIR fluorescence imaging is able to detect tumor EGFR and HER2 expression based upon the highly potent bispecific peptide probe.

In vivo study on the biocompatibility of chitosan-hydroxyapatite film depending on degree of deacetylation.

Science.gov (United States)

Jeong, Ki-Jae; Song, Younseong; Shin, Hye-Ri; Kim, Ji Eun; Kim, Jeonghyo; Sun, Fangfang; Hwang, Dae-Youn; Lee, Jaebeom

2017-06-01

Chitosan, produced from chitin, is one of the polymers with promising applications in various fields. However, despite diverse research studies conducted on its biocompatibility, its uses are still limited. The main reason is the degree of deacetylation (DOD), which represents the proportion of deacetylated units in the polymer and is directly correlated with its biocompatibility property. In this article, the in vivo biocompatibility of three chitosan-hydroxyapatite composite films composed of chitosan with different DOD values was investigated by traditional biological protocols and novel optical spectroscopic analyses. The DOD of the chitosan obtained from three different manufacturers was estimated and calculated by Raman spectroscopy, Fourier transform infrared spectroscopy, and proton nuclear magnetic resonance spectroscopy. The chitosan with the higher DOD induced a higher incidence of inflammation in skin cells. The amino group density, biodegradability, and crystallinity of chitosan are the three possible factors that need to be considered when determining the biocompatibility of the films for in vivo application, as they led to complicated biological results, resulting in either better or worse inflammation even when using chitosan products with the same DOD. This basic study on the relationship between the DOD and inflammation is valuable for the development of further chitosan-based researches. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1637-1645, 2017. © 2017 Wiley Periodicals, Inc.

Functional and biocompatibility performances of an integrated Maglev pump-oxygenator.

Science.gov (United States)

Zhang, Tao; Cheng, Guangming; Koert, Andrew; Zhang, Juntao; Gellman, Barry; Yankey, G Kwame; Satpute, Aditee; Dasse, Kurt A; Gilbert, Richard J; Griffith, Bartley P; Wu, Zhongjun J

2009-01-01

To provide respiratory support for patients with lung failure, a novel compact integrated pump-oxygenator is being developed. The functional and biocompatibility performances of this device are presented. The pump-oxygenator is designed by combining a magnetically levitated pump/rotor with a uniquely configured hollow fiber membrane bundle to create an assembly free, ultracompact, all-in-one system. The hemodynamics, gas transfer and biocompatibility performances of this novel device were investigated both in vitro in a circulatory flow loop and in vivo in an ovine animal model. The in vitro results showed that the device was able to pump blood flow from 2 to 8 L/min against a wide range of pressures and to deliver an oxygen transfer rate more than 300 mL/min at a blood flow of 6 L/min. Blood damage tests demonstrated low hemolysis (normalized index of hemolysis [NIH] approximately 0.04) at a flow rate of 5 L/min against a 100-mm Hg afterload. The data from five animal experiments (4 h to 7 days) demonstrated that the device could bring the venous blood to near fully oxygen-saturated condition (98.6% +/- 1.3%). The highest oxygen transfer rate reached 386 mL/min. The gas transfer performance was stable over the study duration for three 7-day animals. There was no indication of blood damage. The plasma free hemoglobin and platelet count were within the normal ranges. No gross thrombus is found on the explanted pump components and fiber surfaces. Both in vitro and in vivo results demonstrated that the newly developed pump-oxygenator can achieve sufficient blood flow and oxygen transfer with excellent biocompatibility.

Designing the nanobiointerface of fluorescent nanodiamonds: highly selective targeting of glioma cancer cells.

Science.gov (United States)

Slegerova, Jitka; Hajek, Miroslav; Rehor, Ivan; Sedlak, Frantisek; Stursa, Jan; Hruby, Martin; Cigler, Petr

2015-01-14

Core-shell nanoparticles based on fluorescent nanodiamonds coated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell were developed for background-free near-infrared imaging of cancer cells. The particles showed excellent colloidal stability in buffers and culture media. After conjugation with a cyclic RGD peptide they selectively targeted integrin αvβ3 receptors on glioblastoma cells with high internalization efficacy.

Far Western: probing membranes.

Science.gov (United States)

Einarson, Margret B; Pugacheva, Elena N; Orlinick, Jason R

2007-08-01

INTRODUCTIONThe far-Western technique described in this protocol is fundamentally similar to Western blotting. In Western blots, an antibody is used to detect a query protein on a membrane. In contrast, in a far-Western blot (also known as an overlay assay) the antibody is replaced by a recombinant GST fusion protein (produced and purified from bacteria), and the assay detects the interaction of this protein with target proteins on a membrane. The membranes are washed and blocked, incubated with probe protein, washed again, and subjected to autoradiography. The GST fusion (probe) proteins are often labeled with (32)P; alternatively, the membrane can be probed with unlabeled GST fusion protein, followed by detection using commercially available GST antibodies. The nonradioactive approach is substantially more expensive (due to the purchase of antibody and detection reagents) than using radioactively labeled proteins. In addition, care must be taken to control for nonspecific interactions with GST alone and a signal resulting from antibody cross-reactivity. In some instances, proteins on the membrane are not able to interact after transfer. This may be due to improper folding, particularly in the case of proteins expressed from a phage expression library. This protocol describes a way to overcome this by washing the membrane in denaturation buffer, which is then serially diluted to permit slow renaturation of the proteins.

Development of X-ray excitable luminescent probes for scanning X-ray microscopy

International Nuclear Information System (INIS)

Moronne, M.M.

1999-01-01

Transmission soft X-ray microscopy is now capable of achieving resolutions that are typically 5 times better than the best-visible light microscopes. With expected improvements in zone plate optics, an additional factor of two may be realized within the next few years. Despite the high resolution now available with X-ray microscopes and the high X-ray contrast provided by biological molecules in the soft X-ray region (λ=2-5 nm), molecular probes for localizing specific biological targets have been lacking. To circumvent this problem, X-ray excitable molecular probes are needed that can target unique biological features. In this paper we report our initial results on the development of lanthanide-based fluorescent probes for biological labeling. Using scanning luminescence X-ray microscopy (SLXM, Jacobsen et al., J. Microscopy 172 (1993) 121-129), we show that lanthanide organo-polychelate complexes are sufficiently bright and radiation resistant to be the basis of a new class of X-ray excitable molecular probes capable of providing at least a fivefold improvement in resolution over visible light microscopy. Lanthanide probes, able to bind 80-100 metal ions per molecule, were found to give strong luminescent signals with X-ray doses exceeding 10 8 Gy, and were used to label actin stress fibers and in vitro preparations of polymerized tubulin. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

Surface Modification of SiO2 Microchannels with Biocompatible Polymer Using Supercritical Carbon Dioxide

Science.gov (United States)

Saito, Tatsuro; Momose, Takeshi; Hoshi, Toru; Takai, Madoka; Ishihara, Kazuhiko; Shimogaki, Yukihiro

2010-11-01

The surface of 500-mm-long microchannels in SiO2 microchips was modified using supercritical CO2 (scCO2) and a biocompatible polymer was coated on it to confer biocompatibility to the SiO2 surface. In this method, the SiO2 surface of a microchannel was coated with poly(ethylene glycol monomethacrylate) (PEGMA) as the biocompatible polymer using allyltriethoxysilane (ATES) as the anchor material in scCO2 as the reactive medium. Results were compared with those using the conventional wet method. The surface of a microchannel could not be modified by the wet method owing to the surface tension and viscosity of the liquid, but it was modified uniformly by the scCO2 method probably owing to the near-zero surface tension, low viscosity, and high diffusivity of scCO2. The effect of the surface modification by the scCO2 method to prevent the adsorption of protein was as high as that of the modification by the wet method. Modified microchips can be used in biochemical and medical analyses.

Frontiers in biomaterials the design, synthetic strategies and biocompatibility of polymer scaffolds for biomedical application

CERN Document Server

Cao, Shunsheng

2014-01-01

Frontiers in Biomaterials: The Design, Synthetic Strategies and Biocompatibility of Polymer Scaffolds for Biomedical Application, Volume 1" highlights the importance of biomaterials and their interaction with biological system. The need for the development of biomaterials as scaffold for tissue regeneration is driven by the increasing demands for materials that mimic functions of extracellular matrices of body tissues.This ebook covers the latest challenges on the biocompatibility of scaffold overtime after implantation and discusses the requirement of innovative technologies and strategies f

BIOCOMPATIBILITY AND TISSUE REGENERATING CAPACITY OF CROSS-LINKED DERMAL SHEEP COLLAGEN

NARCIS (Netherlands)

VANWACHEM, PB; VANLUYN, MJA; DAMINK, LHHO; DIJKSTRA, PJ; FEIJEN, J; NIEUWENHUIS, P

The biocompatibility and tissue regenerating capacity of four crosslinked dermal sheep collagens (DSC) was studied. In vitro, the four DSC versions were found to be noncytotoxic or very low in cytoxicity. After subcutaneous implantation in rats, hexamethylenediisocyanate-crosslinked DSC (HDSC)

Radioiodine labeled CdSe/CdS quantum dots. Lectin targeted dual probes

Energy Technology Data Exchange (ETDEWEB)

Akca, Ozlet; Unak, Perihan; Medine, E. Ilker; Kilcar, Ayfer Yurt; Ichedef, Cigdem [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications; Sakarya, Serhan [Adnan Menderes Univ., Aydin (Turkey). Dept. of Nuclear Medicine; Bekis, Recep [Dokuz Eyluel Univ., Izmir (Turkey). Dept. of Nuclear Medicine; Timur, Suna [Ege Univ., Izmir (Turkey). Biochemistry Dept.

2014-11-01

CdSe/CdS quantum dots (QD) were synthesized and bioconjugated with Sambucus nigra agglutinin (SNA) lectin (Lec). Mannose triflate and cysteamine molecules (MTC) were also utilized to prepare MTC-QDs and MTC-QDs-Lec probes as well as Lec bound QDs. Afterwards; potential use of these nanoparticles as radiolabeled fluorescence nano-probes for the cell imaging studies has been investigated. Biological activities of {sup 125}I{sup -}, {sup 125}I-MTC-QDs, MTC-QDs- Lec-{sup 125}I, QDs-Lec-{sup 125}I and Lec-{sup 125}I were examined on various cancer cell lines such as Caco-2, MCF-7 and A-549 in terms of cell incorporation. QDs-Lec-{sup 125}I exhibited the highest cell incorporation on whole cell lines. In addition, the QDs-Lec-{sup 131}I, was used for in vivo imaging. The whole body distribution of the radiolabeled QDs on New Zealand rabbits and Balb C mice were examined by taking dynamic and static images. Radioactivity cleared from the kidneys and the bladder, while significant amount radioactivity was retained in the heart and liver within 24 h.

Evaluation of biocompatibility and administration site reactogenicity of polyanhydride-particle-based platform for vaccine delivery.

Science.gov (United States)

Huntimer, Lucas; Ramer-Tait, Amanda E; Petersen, Latrisha K; Ross, Kathleen A; Walz, Katherine A; Wang, Chong; Hostetter, Jesse; Narasimhan, Balaji; Wannemuehler, Michael J

2013-02-01

Efficacy, purity, safety, and potency are important attributes of vaccines. Polyanhydride particles represent a novel class of vaccine adjuvants and delivery platforms that have demonstrated the ability to enhance the stability of protein antigens as well as elicit protective immunity against bacterial pathogens. This work aims to elucidate the biocompatibility, inflammatory reactions, and particle effects on mice injected with a 5 mg dose of polyanhydride nanoparticles via common parenteral routes (subcutaneous and intramuscular). Independent of polymer chemistry, nanoparticles more effectively disseminated away from the injection site as compared to microparticles, which exhibited a depot effect. Using fluorescent probes, the in vivo distribution of three formulations of nanoparticles, following subcutaneous administration, indicated migration away from the injection site. Less inflammation was observed at the injection sites of mice-administered nanoparticles as compared to Alum and incomplete Freund's adjuvant. Furthermore, histological evaluation revealed minimal adverse injection site reactions and minimal toxicological effects associated with the administration of nanoparticles at 30 days post-administration. Collectively, these results demonstrate that polyanhydride nanoparticles do not induce inflammation as a cumulative effect of particle persistence or degradation and are, therefore, a viable candidate for a vaccine delivery platform. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A review of hydroxyapatite-based coating techniques: Sol-gel and electrochemical depositions on biocompatible metals.

Science.gov (United States)

Asri, R I M; Harun, W S W; Hassan, M A; Ghani, S A C; Buyong, Z

2016-04-01

New promising techniques for depositing biocompatible hydroxyapatite-based coatings on biocompatible metal substrates for biomedical applications have continuously been exploited for more than two decades. Currently, various experimental deposition processes have been employed. In this review, the two most frequently used deposition processes will be discussed: a sol-gel dip coating and an electrochemical deposition. This study deliberates the surface morphologies and chemical composition, mechanical performance and biological responses of sol-gel dip coating as well as the electrochemical deposition for two different sample conditions, with and without coating. The review shows that sol-gel dip coatings and electrochemical deposition were able to obtain the uniform and homogeneous coating thickness and high adherent biocompatible coatings even in complex shapes. It has been accepted that both coating techniques improve bone strength and initial osseointegration rate. The main advantages and limitations of those techniques of hydroxyapatite-based coatings are presented. Furthermore, the most significant challenges and critical issues are also highlighted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identification and quantification of Bifidobacterium species isolated from food with genus-specific 16S rRNA-targeted probes by colony hybridization and PCR.

Science.gov (United States)

Kaufmann, P; Pfefferkorn, A; Teuber, M; Meile, L

1997-04-01

A Bifidobacterium genus-specific target sequence in the V9 variable region of the 16S rRNA has been elaborated and was used to develop a hybridization probe. The specificity of this probe, named lm3 (5'-CGGGTGCTI*CCCACTTTCATG-3'), was used to identify all known type strains and distinguish them from other bacteria. All of the 30 type strains of Bifidobacterium which are available at the German culture collection Deutsche Sammlung von Mikroorganismen und Zellkulturen, 6 commercially available production strains, and 34 closely related relevant strains (as negative controls) were tested. All tested bifidobacteria showed distinct positive signals by colony hybridization, whereas all negative controls showed no distinct dots except Gardnerella vaginalis DSM4944 and Propionibacterium freudenreichii subsp. shermanii DSM4902, which gave slight signals. Furthermore, we established a method for isolation and identification of bifidobacteria from food by using a PCR assay without prior isolation of DNA but breaking the cells with proteinase K. By this method, all Bifidobacterium strains lead to a DNA product of the expected size. We also established a quick assay to quantitatively measure Bifidobacterium counts in food and feces by dilution plating and colony hybridization. We were able to demonstrate that 2.1 x 10(6) to 2.3 x 10(7) colonies/g of sour milk containing bifidobacteria hybridized with the specific nucleotide probe. With these two methods, genus-specific colony hybridization and genus-specific PCR, it is now possible to readily and accurately detect any bifidobacteria in food and fecal samples and to discriminate between them and members of other genera.

Alternating Magnetic Field Controlled, Multifunctional Nano-Reservoirs: Intracellular Uptake and Improved Biocompatibility

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GhoshMitra Somesree

2009-01-01

Full Text Available Abstract Biocompatible magnetic nanoparticles hold great therapeutic potential, but conventional particles can be toxic. Here, we report the synthesis and alternating magnetic field dependent actuation of a remotely controllable, multifunctional nano-scale system and its marked biocompatibility with mammalian cells. Monodisperse, magnetic nanospheres based on thermo-sensitive polymer network poly(ethylene glycol ethyl ether methacrylate-co-poly(ethylene glycol methyl ether methacrylate were synthesized using free radical polymerization. Synthesized nanospheres have oscillating magnetic field induced thermo-reversible behavior; exhibiting desirable characteristics comparable to the widely used poly-N-isopropylacrylamide-based systems in shrinkage plus a broader volumetric transition range. Remote heating and model drug release were characterized for different field strengths. Nanospheres containing nanoparticles up to an iron concentration of 6 mM were readily taken up by neuron-like PC12 pheochromocytoma cells and had reduced toxicity compared to other surface modified magnetic nanocarriers. Furthermore, nanosphere exposure did not inhibit the extension of cellular processes (neurite outgrowth even at high iron concentrations (6 mM, indicating minimal negative effects in cellular systems. Excellent intracellular uptake and enhanced biocompatibility coupled with the lack of deleterious effects on neurite outgrowth and prior Food and Drug Administration (FDA approval of PEG-based carriers suggest increased therapeutic potential of this system for manipulating axon regeneration following nervous system injury.

Dispersion of multi-walled carbon nanotubes in biocompatible dispersants

International Nuclear Information System (INIS)

Piret, J.-P.; Detriche, S.; Vigneron, R.; Vankoningsloo, S.; Rolin, S.; Mejia Mendoza, J. H.; Masereel, B.; Lucas, S.; Delhalle, J.; Luizi, F.; Saout, C.; Toussaint, O.

2010-01-01

Owing to their phenomenal electrical and mechanical properties, carbon nanotubes (CNT) have been an area of intense research since their discovery in 1991. Different applications for these nanoparticles have been proposed, among others, in electronics and optics but also in the medical field. In parallel, emerging studies have suggested potential toxic effects of CNT while others did not, generating some conflicting outcomes. These discrepancies could be, in part, due to different suspension approaches used and to the agglomeration state of CNT in solution. In this study, we described a standardized protocol to obtain stable CNT suspensions, using two biocompatible dispersants (Pluronic F108 and hydroxypropylcellulose) and to estimate the concentration of CNT in solution. CNT appear to be greatly individualized in these two dispersants with no detection of remaining bundles or agglomerates after sonication and centrifugation. Moreover, CNT remained perfectly dispersed when added to culture medium used for in vitro cell experiments. We also showed that Pluronic F108 is a better dispersant than hydroxypropylcellulose. In conclusion, we have developed a standardized protocol using biocompatible surfactants to obtain reproducible and stable multi-walled carbon nanotubes suspensions which can be used for in vitro or in vivo toxicological studies.

Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

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Qingqing Meng

2013-01-01

Full Text Available Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.

Natural material-decorated mesoporous silica nanoparticle container for multifunctional membrane-controlled targeted drug delivery

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Hu Y

2017-11-01

Full Text Available Yan Hu,1 Lei Ke,2 Hao Chen,1 Ma Zhuo,1 Xinzhou Yang,1 Dan Zhao,1 Suying Zeng,1 Xincai Xiao1 1Department of Pharmaceutics, School of Pharmaceutical Science, South-Central University for Nationalities, 2Department of Medicinal Chemistry, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China Abstract: To avoid the side effects caused by nonspecific targeting, premature release, weak selectivity, and poor therapeutic efficacy of current nanoparticle-based systems used for drug delivery, we fabricated natural material-decorated nanoparticles as a multifunctional, membrane-controlled targeted drug delivery system. The nanocomposite material coated with a membrane was biocompatible and integrated both specific tumor targeting and responsiveness to stimulation, which improved transmission efficacy and controlled drug release. Mesoporous silica nanoparticles (MSNs, which are known for their biocompatibility and high drug-loading capacity, were selected as a model drug container and carrier. The membrane was established by the polyelectrolyte composite method from chitosan (CS which was sensitive to the acidic tumor microenvironment, folic acid-modified CS which recognizes the folate receptor expressed on the tumor cell surface, and a CD44 receptor-targeted polysaccharide hyaluronic acid. We characterized the structure of the nanocomposite as well as the drug release behavior under the control of the pH-sensitive membrane switch and evaluated the antitumor efficacy of the system in vitro. Our results provide a basis for the design and fabrication of novel membrane-controlled nanoparticles with improved tumor-targeting therapy. Keywords: multifunctional, membrane-controlled, natural materials, mesoporous silica nanoparticles, targeted drug delivery

Efficient oligonucleotide probe selection for pan-genomic tiling arrays

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Zhang Wei

2009-09-01

Full Text Available Abstract Background Array comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome. Results This paper presents a new probe selection algorithm (PanArray that can tile multiple whole genomes using a minimal number of probes. Unlike arrays built on clustered gene families, PanArray uses an unbiased, probe-centric approach that does not rely on annotations, gene clustering, or multi-alignments. Instead, probes are evenly tiled across all sequences of the pan-genome at a consistent level of coverage. To minimize the required number of probes, probes conserved across multiple strains in the pan-genome are selected first, and additional probes are used only where necessary to span polymorphic regions of the genome. The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage. Conclusion PanArray is an oligonucleotide probe selection algorithm for tiling multiple genome sequences using a minimal number of probes. It is capable of fully tiling all genomes of a species on

Membrane biocompatibility does not affect whole body protein metabolism during dialysis

NARCIS (Netherlands)

Veeneman, JM; Kingma, HA; Stellaard, F; de Jong, PE; Reijngoud, DJ; Huisman, RM

2005-01-01

Background: Protein-calorie malnutrition is present in 30-50% of dialysis patients. The lack of biocompatibility of the dialysis membrane, which results in low-grade inflammation, could be responsible for this malnutrition. We investigated whether protein-energy malnutrition could be partly due to

Synthesis, characterization and in vitro evaluation of exquisite targeting SPIONs–PEG–HER in HER2+ human breast cancer cells

International Nuclear Information System (INIS)

Almaki, Javad Hamzehalipour; Nasiri, Rozita; Idris, Ani; Majid, Fadzilah Adibah Abdul; Wong, Tet Soon; Salouti, Mojtaba; Dabagh, Shadab; Marvibaigi, Mohsen; Amini, Neda

2016-01-01

A stable, biocompatible and exquisite SPIONs–PEG–HER targeting complex was developed. Initially synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were silanized using 3-aminopropyltrimethoxysilane (APS) as the coupling agent in order to allow the covalent bonding of polyethylene glycol (PEG) to the SPIONs to improve the biocompatibility of the SPIONs. SPIONs–PEG were then conjugated with herceptin (HER) to permit the SPIONs–PEG–HER to target the specific receptors expressed over the surface of the HER2+ metastatic breast cancer cells. Each preparation step was physico-chemically analyzed and characterized by a number of analytical methods including AAS, FTIR spectroscopy, XRD, FESEM, TEM, DLS and VSM. The biocompatibility of SPIONs–PEG–HER was evaluated in vitro on HSF-1184 (human skin fibroblast cells), SK-BR-3 (human breast cancer cells, HER+), MDA-MB-231 (human breast cancer cells, HER−) and MDA-MB-468 (human breast cancer cells, HER−) cell lines by performing MTT and trypan blue assays. The hemolysis analysis results of the SPIONs–PEG–HER and SPIONs–PEG did not indicate any sign of lysis while in contact with erythrocytes. Additionally, there were no morphological changes seen in RBCs after incubation with SPIONs–PEG–HER and SPIONs–PEG under a light microscope. The qualitative and quantitative in vitro targeting studies confirmed the high level of SPION–PEG–HER binding to SK-BR-3 (HER2+ metastatic breast cancer cells). Thus, the results reflected that the SPIONs–PEG–HER can be chosen as a favorable biomaterial for biomedical applications, chiefly magnetic hyperthermia, in the future. (paper)

Biocompatibility study on Ni-free Ti-based and Zr-based bulk metallic glasses

Energy Technology Data Exchange (ETDEWEB)

Li, T.H. [Institute of Material Science and Engineering, National Central University, Taoyuan, Taiwan (China); Wong, P.C. [Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan (China); Chang, S.F. [Department of Mechanical Engineering, National Central University, Taoyuan, Taiwan (China); Tsai, P.H. [Institute of Material Science and Engineering, National Central University, Taoyuan, Taiwan (China); Jang, J.S.C., E-mail: jscjang@ncu.edu.tw [Institute of Material Science and Engineering, National Central University, Taoyuan, Taiwan (China); Department of Mechanical Engineering, National Central University, Taoyuan, Taiwan (China); Huang, J.C. [Department of Materials and Optoelectronic Science, National Sun Yat-Sen University, Kaohsiung, Taiwan (China)

2017-06-01

Safety and reliability are crucial issues for medical instruments and implants. In the past few decays, bulk metallic glasses (BMGs) have drawn attentions due to their superior mechanical properties, good corrosion resistance, antibacterial and good biocompatibility. However, most Zr-based and Ti-based BMGs contain Ni as an important element which is prone to human allergy problem. In this study, the Ni-free Ti-based and Zr-based BMGs, Ti{sub 40}Zr{sub 10}Cu{sub 36}Pd{sub 14}, and Zr{sub 48}Cu{sub 36}Al{sub 8}Ag{sub 8}, were selected for systematical evaluation of their biocompatibility. Several biocompatibility tests, co-cultural with L929 murine fibroblast cell line, were carried out on these two BMGs, as well as the comparison samples of Ti6Al4V and pure Cu. The results in terms of cellular adhesion, cytotoxicity, and metallic ion release affection reveal that the Ti{sub 40}Zr{sub 10}Cu{sub 36}Pd{sub 14} BMG and Ti6Al4V exhibit the optimum biocompatibility; cells still being attached on the petri dish with good adhesion and exhibiting the spindle shape after direct contact test. Furthermore, the Ti{sub 40}Zr{sub 10}Cu{sub 36}Pd{sub 14} BMG showed very low Cu ion release level, in agreement with the MTT results. Based on the current findings, it is believed that Ni-free Ti-based BMG can act as an ideal candidate for medical implant. - Highlight: • Ni-free bulk metallic glass is promising material for medical implants. • Ni-free Ti-based BMG presents similar cellular adhesion as Ti6Al4V. • Ni-free Ti-based BMG shows less cytotoxicity, and metallic ion release than Ti6Al4V.

Molecular Composition Analysis of Distant Targets

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National Aeronautics and Space Administration — We propose a system capable of probing the molecular composition of cold solar system targets such as asteroids, comets, planets and moons from a distant vantage....

New molecular probes of vascular inflammation

International Nuclear Information System (INIS)

Molecular Cardiovascular Imaging, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (Department of Nuclear Medicine, University Hospital Münster, Münster, and DFG CRC 656 Molecular Cardiovascular Imaging, Westfälische Wilhelms University Münster, Münster, (Germany))" >VRACHIMIS, Alexis; HONOLD, Lisa; Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (European Institute of Molecular Imaging, Westfälische Wilhelms University Münster, Münster, and DFG EXC 1003 Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" >FAUST, Andreas; Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (European Institute of Molecular Imaging, Westfälische Wilhelms University Münster, Münster, and DFG EXC 1003 Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" >HERMANN, Sven; SCHÄFERS, Michael

2016-01-01

New molecular imaging approaches featuring the assessment of inflammatory processes in the vascular wall on top of existing anatomic and functional vessel imaging procedures could emerge as decisive tools for the understanding and prevention of cardiovascular events. In this respect imaging approaches addressing specific molecular and cellular targets in atherosclerosis are of high interest. This review summarizes the rationale and current status of nuclear imaging probes which possess high translational potential.

RTV silicone rubber surface modification for cell biocompatibility by negative-ion implantation

International Nuclear Information System (INIS)

Zheng, Chenlong; Wang, Guangfu; Chu, Yingjie; Xu, Ya; Qiu, Menglin; Xu, Mi

2016-01-01

Highlights: • The radiation effect has a greater influence than doping effect on the hydrophilicity of RTV SR. • The implanted ions result in a new surface atomic bonding state and morphology. • Generating hydrophilic functional groups is a reason for the improved cell biocompatibility. • The micro roughness makes the hydrophilicity should be reduced due to the lotus effect. • Cell culture demonstrates that negative-ion implantation can improve biocompatibility. - Abstract: A negative cluster ion implantation system was built on the injector of a GIC4117 tandem accelerator. Next, the system was used to study the surface modification of room temperature vulcanization silicone rubber (RTV SR) for cell biocompatibility. The water contact angle was observed to decrease from 117.6° to 99.3° as the C_1"− implantation dose was increased to 1 × 10"1"6 ions/cm"2, and the effects of C_1"−, C_2"− and O_1"− implantation result in only small differences in the water contact angle at 3 × 10"1"5 ions/cm"2. These findings indicate that the hydrophilicity of RTV SR improves as the dose is increased and that the radiation effect has a greater influence than the doping effect on the hydrophilicity. There are two factors influence hydrophilicity of RTV: (1) based on the XPS and ATR-FTIR results, it can be inferred that ion implantation breaks the hydrophobic functional groups (Si−CH_3, Si−O−Si, C−H) of RTV SR and generates hydrophilic functional groups (−COOH, −OH, Si−(O)_x (x = 3,4)). (2) SEM reveals that the implanted surface of RTV SR appears the micro roughness such as cracks and wrinkles. The hydrophilicity should be reduced due to the lotus effect (Zhou Rui et al., 2009). These two factors cancel each other out and make the C-implantation sample becomes more hydrophilic in general terms. Finally, cell culture demonstrates that negative ion-implantation is an effective method to improve the cell biocompatibility of RTV SR.

Biocompatibility of 17-4 PH stainless steel foam for implant applications.

Science.gov (United States)

Mutlu, Ilven; Oktay, Enver

2011-01-01

In this study, biocompatibility of 17-4 PH stainless steel foam for biomedical implant applications was investigated. 17-4 PH stainless steel foams having porosities in the range of 40-82% with an average pore size of around 600 μm were produced by space holder-sintering technique. Sintered foams were precipitation hardened for times of 1-6 h at temperatures between 450-570 °C. Compressive yield strength and Young's modulus of aged stainless steel foams were observed to vary between 80-130 MPa and 0.73-1.54 GPa, respectively. Pore morphology, pore size and the mechanical properties of the 17-4 PH stainless steel foams were close to cancellous bone. In vitro evaluations of cytotoxicity of the foams were investigated by XTT and MTT assays and showed sufficient biocompatibility. Surface roughness parameters of the stainless steel foams were also determined to characterize the foams.

Electrogenerated chemiluminescence detection for deoxyribonucleic acid hybridization based on gold nanoparticles carrying multiple probes

International Nuclear Information System (INIS)

Wang Hui; Zhang Chengxiao; Li Yan; Qi Honglan

2006-01-01

A novel sensitive electrogenerated chemiluminescence (ECL) method for the detection deoxyribonucleic acid (DNA) hybridization based on gold nanoparticles carrying multiple probes was developed. Ruthenium bis(2,2'-bipyridine)(2,2'-bipyridine-4,4'-dicarboxylic acid)-N-hydroxysuccinimide ester (Ru(bpy) 2 (dcbpy)NHS) was used as a ECL label and gold nanoparticle as a carrier. Probe single strand DNA (ss-DNA) was self-assembled at the 3'-terminal with a thiol group to the surface of gold nanoparticle and covalently labeled at the 5'-terminal of a phosphate group with Ru(bpy) 2 (dcbpy)NHS and the resulting conjugate (Ru(bpy) 2 (dcbpy)NHS)-ss-DNA-Au, was taken as a ECL probe. When target analyte ss-DNA was immobilized on a gold electrode by self-assembled monolayer technique and then hybridized with the ECL probe to form a double-stranded DNA (ds-DNA), a strong ECL response was electrochemically generated. The ECL intensity was linearly related to the concentration of the complementary sequence (target ss-DNA) in the range from 1.0 x 10 -11 to 1.0 x 10 -8 mol L -1 , and the linear regression equation was S = 57301 + 4579.6 lg C (unit of C is mol L -1 ). A detection limit of 5.0 x 10 -12 mol L -1 for target ss-DNA was achieved. The ECL signal generated from many reporters of ECL probe prepared is greatly amplified, compared to the convention scheme which is based on one reporter per hybridization event

Biocompatibility evaluation of cigarette and carbon papers used in repair of traumatic tympanic membrane perforations: experimental study.

Science.gov (United States)

Altuntaş, Emine Elif; Sümer, Zeynep

2013-01-01

The purposes of this study were to investigate the biocompatibility of two different paper patches (carbon and cigarette papers) and compare the adhesion and proliferation features of L929 fibroblast cells by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT Test) test and scanning electron microscopy (SEM). In this study, time-dependent cytotoxic effects of cigarette and carbon papers used in repairing small traumatic TM perforations were investigated in vitro by using MTT test. And also adhesion and spreading of cells over disk surface were observed by SEM. Cytotoxicity test carried out by MTT analysis on leakage products collected from two types of paper patches at the end of 24 and 48 h revealed no cytotoxicity (P > 0.05). In SEM studies, it was observed that cells started to proliferate over disk surface as a result of 48-h incubation, and SEM revealed that the cell proliferation over cigarette paper was more compared to the one over carbon paper. We believe that this is the first study where biocompatibility and adhesion features of carbon and cigarette paper have been studied by using L929 fibroblast cell culture. As a result, biocompatibility of cigarette paper and also whether cigarette paper was superior to carbon paper in cell attachment and biocompatibility were studied. It was found, by MTT test and SEM test, that cigarette paper had a higher biocompatibility and cell attachment, and thus cigarette paper should be the patch to be preferred in cases where TM perforations are repaired by paper-patch method.

Biocompatible nanomaterials based on dendrimers, hydrogels and hydrogel nanocomposites for use in biomedicine

Science.gov (United States)

Khoa Nguyen, Cuu; Quyen Tran, Ngoc; Phuong Nguyen, Thi; Hai Nguyen, Dai

2017-03-01

Over the past decades, biopolymer-based nanomaterials have been developed to overcome the limitations of other macro- and micro- synthetic materials as well as the ever increasing demand for the new materials in nanotechnology, biotechnology, biomedicine and others. Owning to their high stability, biodegradability, low toxicity, and biocompatibility, biopolymer-based nanomaterials hold great promise for various biomedical applications. The pursuit of this review is to briefly describe our recent studies regarding biocompatible biopolymer-based nanomaterials, particularly in the form of dendrimers, hydrogels, and hydrogel composites along with the synthetic and modification approaches for the utilization in drug delivery, tissue engineering, and biomedical implants. Moreover, in vitro and in vivo studies for the toxicity evaluation are also discussed.

Smart optical probes for near-infrared fluorescence imaging of Alzheimer's disease pathology

International Nuclear Information System (INIS)

Raymond, Scott B.; Bacskai, Brian J.; Skoch, Jesse; Hills, Ivory D.; Swager, Timothy M.; Nesterov, Evgueni E.

2008-01-01

Near-infrared fluorescent probes for amyloid-beta (Aβ) are an exciting option for molecular imaging in Alzheimer's disease research and may translate to clinical diagnostics. However, Aβ-targeted optical probes often suffer from poor specificity and slow clearance from the brain. We are designing smart optical probes that emit characteristic fluorescence signal only when bound to Aβ. We synthesized a family of dyes and tested Aβ-binding sensitivity with fluorescence spectroscopy and tissue-staining. Select compounds exhibited Aβ-dependent changes in fluorescence quantum yield, lifetime, and emission spectra that may be imaged microscopically or in vivo using new lifetime and spectral fluorescence imaging techniques. Smart optical probes that turn on when bound to Aβ will improve amyloid detection and may enable quantitative molecular imaging in vivo. (orig.)

Green chemistry approach for the synthesis of biocompatible graphene

Directory of Open Access Journals (Sweden)

Gurunathan S

2013-07-01

Full Text Available Sangiliyandi Gurunathan, Jae Woong Han, Jin-Hoi Kim Department of Animal Biotechnology, Konkuk University, Seoul, South Korea Background: Graphene is a single-atom thick, two-dimensional sheet of hexagonally arranged carbon atoms isolated from its three-dimensional parent material, graphite. One of the most common methods for preparation of graphene is chemical exfoliation of graphite using powerful oxidizing agents. Generally, graphene is synthesized through deoxygenation of graphene oxide (GO by using hydrazine, which is one of the most widespread and strongest reducing agents. Due to the high toxicity of hydrazine, it is not a promising reducing agent in large-scale production of graphene; therefore, this study focused on a green or sustainable synthesis of graphene and the biocompatibility of graphene in primary mouse embryonic fibroblast cells (PMEFs. Methods: Here, we demonstrated a simple, rapid, and green chemistry approach for the synthesis of reduced GO (rGO from GO using triethylamine (TEA as a reducing agent and stabilizing agent. The obtained TEA reduced GO (TEA-rGO was characterized by ultraviolet (UV–visible absorption spectroscopy, X-ray diffraction (XRD, particle size dynamic light scattering (DLS, scanning electron microscopy (SEM, Raman spectroscopy, and atomic force microscopy (AFM. Results: The transition of graphene oxide to graphene was confirmed by UV–visible spectroscopy. XRD and SEM were used to investigate the crystallinity of graphene and the surface morphologies of prepared graphene respectively. The formation of defects further supports the functionalization of graphene as indicated in the Raman spectrum of TEA-rGO. Surface morphology and the thickness of the GO and TEA-rGO were analyzed using AFM. The presented results suggest that TEA-rGO shows significantly more biocompatibility with PMEFs cells than GO. Conclusion: This is the first report about using TEA as a reducing as well as a stabilizing agent for the

Radial-probe EBUS for the diagnosis of peripheral pulmonary lesions

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Marcia Jacomelli

Full Text Available ABSTRACT Objective: Conventional bronchoscopy has a low diagnostic yield for peripheral pulmonary lesions. Radial-probe EBUS employs a rotating ultrasound transducer at the end of a probe that is passed through the working channel of the bronchoscope. Radial-probe EBUS facilitates the localization of peripheral pulmonary nodules, thus increasing the diagnostic yield. The objective of this study was to present our initial experience using radial-probe EBUS in the diagnosis of peripheral pulmonary lesions at a tertiary hospital. Methods: We conducted a retrospective analysis of 54 patients who underwent radial-probe EBUS-guided bronchoscopy for the investigation of pulmonary nodules or masses between February of 2012 and September of 2013. Radial-probe EBUS was performed with a flexible 20-MHz probe, which was passed through the working channel of the bronchoscope and advanced through the bronchus to the target lesion. For localization of the lesion and for collection procedures (bronchial brushing, transbronchial needle aspiration, and transbronchial biopsy, we used fluoroscopy. Results: Radial-probe EBUS identified 39 nodules (mean diameter, 1.9 ± 0.7 cm and 19 masses (mean diameter, 4.1 ± 0.9 cm. The overall sensitivity of the method was 66.7% (79.5% and 25.0%, respectively, for lesions that were visible and not visible by radial-probe EBUS. Among the lesions that were visible by radial-probe EBUS, the sensitivity was 91.7% for masses and 74.1% for nodules. The complications were pneumothorax (in 3.7% and bronchial bleeding, which was controlled bronchoscopically (in 9.3%. Conclusions: Radial-probe EBUS shows a good safety profile, a low complication rate, and high sensitivity for the diagnosis of peripheral pulmonary lesions.

BIOCOMPATIBILITY OF AZITROMICYN ON CONNECTIVE TISSUE

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Shafira Kurnia

2011-01-01

Full Text Available Background: periodontal disease is commonly caused by bacteria, especially actinomyces actinomycetemcomitans and porphyromonas gingivalis have an abilty enter epithelial cells objectives: to investigate systemic azithromycin as the antibiotic of choice for periodontal disease based on biocomptability test in connective tissue. Material and Methods: BHK 21 cell lines were exposed to 0.025%, 0.050%, 0.075%, and 0.1% azithromycin solution for seven times. Samples were put in incubator for 24 hours. Result: Azitrromycin 0.050%-0.1% showed significant difference between life cells percentage and control, however, azithromycin 0.025% revealed insignificant difference with control. Conclusion: 0.025% azithromycin was considered biocompatible with connective tissue and 0.050% was not.

Biocompatibility of metal injection molded versus wrought ASTM F562 (MP35N) and ASTM F1537 (CCM) cobalt alloys.

Science.gov (United States)

Chen, Hao; Sago, Alan; West, Shari; Farina, Jeff; Eckert, John; Broadley, Mark

2011-01-01

We present a comparative analysis between biocompatibility test results of wrought and Metal Injection Molded (MIM) ASTM F562-02 UNS R30035 (MP35N) and F1537 UNS R31538 (CCM) alloy samples that have undergone the same generic orthopedic implant's mechanical, chemical surface pre-treatment, and a designed pre-testing sample preparation method. Because the biocompatibility properties resulting from this new MIM cobalt alloy process are not well understood, we conducted tests to evaluate cytotoxicity (in vitro), hemolysis (in vitro), toxicity effects (in vivo), tissue irritation level (in vivo), and pyrogenicity count (in vitro) on such samples. We show that our developed MIM MP35N and CCM materials and treatment processes are biocompatible, and that both the MIM and wrought samples, although somewhat different in microstructure and surface, do not show significant differences in biocompatibility.

Studies of biocompatibility of chemically etched CR-39 SSNTDs in view of their applications in alpha-particle radiobiological experiments

International Nuclear Information System (INIS)

Li, W.Y.; Chan, K.F.; Tse, A.K.W.; Fong, W.F.; Yu, K.N.

2006-01-01

Alpha-particle radiobiological experiments involve irradiating cells with alpha particles and require thin biocompatible materials which can record alpha-particle traversals as substrates for cell cultures. The biocompatibilities of chemically etched CR-39 solid-state nuclear track detectors (SSNTDs) using aqueous NaOH or NaOH/ehtanol are studied through the abundance and morphology of the cultured HeLa cells. The wetting properties of these etched CR-39 SSNTDs are also studied. The moderately hydrophobic CR-39 SSNTDs as well as the hydrophobic NaOH/ethanol-etched CR-39 SSNTDs are more biocompatible than the hydrophilic aqueous-NaOH-etched SSNTDs. Too small water contact angles, too large surface energy (γ s ) or the polar component γ s p do not favor the cell culture. On the other hand, the dispersive component γ s d of the surface energy and the ratio γ s p /γ s d do not seem to significantly affect the biocompatibility

Biocompatibility evaluation of magnetosomes formed by Acidithiobacillus ferrooxidans

International Nuclear Information System (INIS)

Yan Lei; Yue Xiaoxuan; Zhang Shuang; Chen Peng; Xu Zhiliang; Li Yang; Li Hongyu

2012-01-01

Magnetite nanocrystal has been extensively used in biomedical field. Currently, an interesting alternative to synthetic magnetic Fe 3 O 4 nanoparticles, called magnetosome, has been found in magnetotactic bacteria. It has been reported that Acidithiobacillus ferrooxidans (At. ferrooxidans) has a potential to synthesize magnetosome. In this study, transmission electron microscope (TEM) was used to analyze the magnetite particles in At. ferrooxidans BY-3. The magnetosomes formed by this bacterium were isolated by a method combining ultracentrifugation and magnetic separation. Crystalline phase and surface functional group of the magnetosomes were investigated by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR), respectively. Biocompatibility of the magnetosomes was systematically evaluated at various concentrations (0.5, 1.0, 2.0 and 4.0 mg/ml). MTT test, hemolysis assay and Micronucleus Test were carried out to evaluate in vitro cytotoxicity, blood toxicity and genotoxicity of magnetosomes, respectively. Under these conditions, magnetosomes showed no cytotoxic, genotoxic and hemolytic effects up to 4.0 mg/ml indicating good biocompatibility of these biological nanoparticles. These revealed that the magnetosomes might have a potential for biotechnological and biomedical applications in the future. - Highlights: ► The production of magnetosomes from At. ferrooxidans has been easily available. ► Several techniques are used to characterize properties of the magnetosomes. ► The magnetosomes have no cytotoxicity, no hemolysis activity and no genotoxicity.

Stealth Biocompatible Si-Based Nanoparticles for Biomedical Applications

Science.gov (United States)

Chaix, Arnaud; Gary-Bobo, Magali; Angeletti, Bernard; Masion, Armand; Da Silva, Afitz; Daurat, Morgane; Lichon, Laure; Garcia, Marcel; Morère, Alain; El Cheikh, Khaled; Durand, Jean-Olivier; Cunin, Frédérique; Auffan, Mélanie

2017-01-01

A challenge regarding the design of nanocarriers for drug delivery is to prevent their recognition by the immune system. To improve the blood residence time and prevent their capture by organs, nanoparticles can be designed with stealth properties using polymeric coating. In this study, we focused on the influence of surface modification with polyethylene glycol and/or mannose on the stealth behavior of porous silicon nanoparticles (pSiNP, ~200 nm). In vivo biodistribution of pSiNPs formulations were evaluated in mice 5 h after intravenous injection. Results indicated that the distribution in the organs was surface functionalization-dependent. Pristine pSiNPs and PEGylated pSiNPs were distributed mainly in the liver and spleen, while mannose-functionalized pSiNPs escaped capture by the spleen, and had higher blood retention. The most efficient stealth behavior was observed with PEGylated pSiNPs anchored with mannose that were the most excreted in urine at 5 h. The biodegradation kinetics evaluated in vitro were in agreement with these in vivo observations. The biocompatibility of the pristine and functionalized pSiNPs was confirmed in vitro on human cell lines and in vivo by cytotoxic and systemic inflammation investigations, respectively. With their biocompatibility, biodegradability, and stealth properties, the pSiNPs functionalized with mannose and PEG show promising potential for biomedical applications. PMID:28946628

Rational Design and Enhanced Biocompatibility of a Dry Adhesive Medical Skin Patch

KAUST Repository

Kwak, Moon Kyu; Jeong, Hoon-Eui; Suh, Kahp Y.

2011-01-01

A new type of medical skin patch is developed that contains high-density, mushroom-like micropillars. Such dry-adhesive micropillars are highly biocompatible, have minimized side effects, and provide reasonable normal adhesion strength. To arrive

Modification of bone graft by blending with lecithin to improve hydrophilicity and biocompatibility

International Nuclear Information System (INIS)

Wang, Y; Cui, F Z; Jiao, Y P; Hu, K; Fan, D D

2008-01-01

Lecithin was blended to improve the hydrophilicity and biocompatibility of bone graft containing poly(l-lactic acid) (PLLA). Solution blending and freeze drying were used to fabricate symmetrical scaffolds containing different percentages of lecithin (lecithin: PLLA = 0, 5, 10 wt%). Scanning electron microscopy showed that the scaffolds maintained the three-dimensional porous structure. A water uptake experiment proved the significant improvement of hydrophilicity of the blend scaffold. With the addition of lecithin, the compressive strength and compressive modulus decreased. When the weight ratio of lecithin to PLLA was up to 10%, the compressive strength was still more than the lower limit of natural cancellous bone. To test the biocompatibility of the scaffolds, cell culture in vitro and subcutaneous implantation in vivo were performed. MC3T3-E1 preosteoblastic cells were cultured on the scaffolds for 7 days. Methylthiazol tetrazolium assay and laser scanning confocal microscopy were used to exhibit proliferation and morphology of the cells. The subcutaneous implantation in rats tested inflammatory response to the scaffolds. The results proved the better biocompatibility and milder inflammatory reactions of the blend scaffold (lecithin: PLLA = 5%) compared with the scaffold without lecithin. The modified scaffold containing lecithin is promising for bone tissue engineering

Impregnation of silver sulfadiazine into bacterial cellulose for antimicrobial and biocompatible wound dressing

International Nuclear Information System (INIS)

Luan, Jiabin; Wu, Jian; Zheng, Yudong; Wang, Guojie; Guo, Jia; Ding, Xun; Song, Wenhui

2012-01-01

Silver sulfadiazine (SSD) is a useful antimicrobial agent for wound treatment. However, recent findings indicate that conventional SSD cream has several drawbacks for use in treatments. Bacterial cellulose (BC) is a promising material for wound dressing due to its outstanding properties of holding water, strength and degradability. Unfortunately, BC itself exhibits no antimicrobial activity. A combination of SSD and BC is envisaged to form a new class of wound dressing with both antimicrobial activity and biocompatibility, which has not been reported to date. To achieve antimicrobial activity, SSD particles were impregnated into BC by immersing BC into SSD suspension after ultrasonication, namely SSD–BC. Parameters influencing SSD–BC impregnation were systematically studied. Optimized conditions of sonication time for no less than 90 min and the proper pH value between 6.6 and 9.0 were suggested. The absorption of SSD onto the BC nanofibrous network was revealed by XRD and SEM analyses. The SSD–BC membranes exhibited significant antimicrobial activities against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus evaluated by the disc diffusion method. In addition, the favorable biocompatibility of SSD–BC was verified by MTT colorimetry, epidermal cell counting method and optical microscopy. The results demonstrate the potential of SSD–BC membranes as a new class of antimicrobial and biocompatible wound dressing. (paper)

Tribological properties, corrosion resistance and biocompatibility of magnetron sputtered titanium-amorphous carbon coatings

Science.gov (United States)

Dhandapani, Vishnu Shankar; Subbiah, Ramesh; Thangavel, Elangovan; Arumugam, Madhankumar; Park, Kwideok; Gasem, Zuhair M.; Veeraragavan, Veeravazhuthi; Kim, Dae-Eun

2016-05-01

Amorphous carbon incorporated with titanium (a-C:Ti) was coated on 316L stainless steel (SS) by magnetron sputtering technique to attain superior tribological properties, corrosion resistance and biocompatibility. The morphology, topography and functional groups of the nanostructured a-C:Ti coatings in various concentrations were analyzed using atomic force microscopy (AFM), Raman, X-Ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). Raman and XPS analyses confirmed the increase in sp2 bonds with increasing titanium content in the a-C matrix. TEM analysis confirmed the composite nature of the coating and the presence of nanostructured TiC for Ti content of 2.33 at.%. This coating showed superior tribological properties compared to the other a-C:Ti coatings. Furthermore, electrochemical corrosion studies were performed against stimulated body fluid medium in which all the a-C:Ti coatings showed improved corrosion resistance than the pure a-C coating. Preosteoblasts proliferation and viability on the specimens were tested and the results showed that a-C:Ti coatings with relatively high Ti (3.77 at.%) content had better biocompatibility. Based on the results of this work, highly durable coatings with good biocompatibility could be achieved by incorporation of optimum amount of Ti in a-C coatings deposited on SS by magnetron sputtering technique.

In vitro and in vivo studies on biocompatibility of carbon fibres

Czech Academy of Sciences Publication Activity Database

Rajzer, I.; Menaszek, E.; Bačáková, Lucie; Rom, M.; Blazewicz, M.

2010-01-01

Roč. 21, č. 9 (2010), s. 2611-2622 ISSN 0957-4530 R&D Projects: GA ČR GA106/09/1000 Institutional research plan: CEZ:AV0Z50110509 Keywords : carbon fibres * biocompatibility Subject RIV: EI - Biotechnology ; Bionics Impact factor: 2.325, year: 2010

Combining portable Raman probes with nanotubes for theranostic applications.

Science.gov (United States)

Bhirde, Ashwinkumar A; Liu, Gang; Jin, Albert; Iglesias-Bartolome, Ramiro; Sousa, Alioscka A; Leapman, Richard D; Gutkind, J Silvio; Lee, Seulki; Chen, Xiaoyuan

2011-01-01

Recently portable Raman probes have emerged along with a variety of applications, including carbon nanotube (CNT) characterization. Aqueous dispersed CNTs have shown promise for biomedical applications such as drug/gene delivery vectors, photo-thermal therapy, and photoacoustic imaging. In this study we report the simultaneous detection and irradiation of carbon nanotubes in 2D monolayers of cancer cells and in 3D spheroids using a portable Raman probe. A portable handheld Raman instrument was utilized for dual purposes: as a CNT detector and as an irradiating laser source. Single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) were dispersed aqueously using a lipid-polymer (LP) coating, which formed highly stable dispersions both in buffer and cell media. The LP coated SWCNT and MWCNT aqueous dispersions were characterized by atomic force microscopy, transmission electron microscopy, dynamic light scattering, Fourier transform infrared spectroscopy and Raman spectroscopy. The cellular uptake of the LP-dispersed SWCNTs and MWCNTs was observed using confocal microscopy, and fluorescein isothiocyanate (FITC)-nanotube conjugates were found to be internalized by ovarian cancer cells by using Z-stack fluorescence confocal imaging. Biocompatibility of SWCNTs and MWCNTs was assessed using a cell viability MTT assay, which showed that the nanotube dispersions did not hinder the proliferation of ovarian cancer cells at the dosage tested. Ovarian cancer cells treated with SWCNTs and MWCNTs were simultaneously detected and irradiated live in 2D layers of cancer cells and in 3D environments using the portable Raman probe. An apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay carried out after laser irradiation confirmed that cell death occurred only in the presence of nanotube dispersions. We show for the first time that both SWCNTs and MWCNTs can be selectively irradiated and detected in cancer cells using a simple

Targeting the Brain with Nanomedicine.

Science.gov (United States)

Rueda, Felix; Cruz, Luis J

2017-01-01

Herein, we review innovative nanomedicine-based approaches for treating, preventing and diagnosing neurodegenerative diseases. We focus on nanoscale systems such as polymeric nanoparticles (NPs), liposomes, micelles and other vehicles (e.g. dendrimers, nanogels, nanoemulsions and nanosuspensions) for targeted delivery of bioactive molecules to the brain. To ensure maximum selectivity for optimal therapeutic or diagnostic results, researchers must employ delivery systems that are non-toxic, biodegradable and biocompatible. This entails: (i) use of "safe" materials, such as polymers or lipids; (ii) targeting to the brain and, specifically, to the desired active site within the brain; (iii) controlled release of the loaded agent; and (iv) use of agents that, once released into the brain, will exhibit the desired pharmacologic activity. Here, we explore the design and preclinical use of representative delivery systems that have been proposed to date. We then analyze the principal challenges that have delayed clinical application of these and other approaches. Lastly, we look at future developments in this area, addressing the needs for increased penetration of the blood brain barrier (BBB), enhanced targeting of specific brain sites, improved therapeutic efficacy and lower neurotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of Ca on microstructure, mechanical and corrosion properties and biocompatibility of Mg-Zn-Ca alloys.

Science.gov (United States)

Yin, Ping; Li, Nian Feng; Lei, Ting; Liu, Lin; Ouyang, Chun

2013-06-01

Zn and Ca were selected as alloying elements to develop an Mg-Zn-Ca alloy system for biomedical application due to their good biocompatibility. The effects of Ca on the microstructure, mechanical and corrosion properties as well as the biocompatibility of the as-cast Mg-Zn-Ca alloys were studied. Results indicate that the microstructure of Mg-Zn-Ca alloys typically consists of primary α-Mg matrix and Ca₂Mg₆Zn₃/Mg₂Ca intermetallic phase mainly distributed along grain boundary. The yield strength of Mg-Zn-Ca alloy increased slightly with the increase of Ca content, whilst its tensile strength increased at first and then decreased. Corrosion tests in the simulated body fluid revealed that the addition of Ca is detrimental to corrosion resistance due to the micro-galvanic corrosion acceleration. In vitro hemolysis and cytotoxicity assessment disclose that Mg-5Zn-1.0Ca alloy has suitable biocompatibility.

Biocompatibility of poly allylamine synthesized by plasma

International Nuclear Information System (INIS)

Colin, E.; Enriquez, M.A.; Olayo, M.G.; Cruz, G.J.; Morales, J.; Olayo, R.

2007-01-01

A study of the electric and hydrophilic properties of poly allylamine (PAI) synthesized by plasma whose structure contains N-H, C-H, C-O and O-H bonds is presented, that promote the biocompatibility with the human body. To study the PAI hydrolytic affinity, solutions of salt concentration similar to those of the human body were used. The results indicate that the solutions modify the charge balance in the surfaces reducing the hydrophobicity in the poly allylamine whose contact angle oscillates among 10 and 16 degrees and the liquid-solid surface tension between 4 and 8 dina/cm. (Author)

Influence of probe motion on laser probe temperature in circulating blood.

Science.gov (United States)

Hehrlein, C; Splinter, R; Littmann, L; Tuntelder, J R; Tatsis, G P; Svenson, R H

1991-01-01

The purpose of this study was to evaluate the effect of probe motion on laser probe temperature in various blood flow conditions. Laser probe temperatures were measured in an in vitro blood circulation model consisting of 3.2 nm-diameter plastic tubes. A 2.0 mm-diameter metal probe attached to a 300 microns optical quartz fiber was coupled to an argon laser. Continuous wave 4 watts and 8 watts of laser power were delivered to the fiber tip corresponding to a 6.7 +/- 0.5 and 13.2 +/- 0.7 watts power setting at the laser generator. The laser probe was either moved with constant velocity or kept stationary. A thermocouple inserted in the lateral portion of the probe was used to record probe temperatures. Probe temperature changes were found with the variation of laser power, probe velocity, blood flow, and duration of laser exposure. Probe motion significantly reduced probe temperatures. After 10 seconds of 4 watts laser power the probe temperature in stagnant blood decreased from 303 +/- 18 degrees C to 113 +/- 17 degrees C (63%) by moving the probe with a velocity of 5 cm/sec. Blood flow rates of 170 ml/min further decreased the probe temperature from 113 +/- 17 degrees C to 50 +/- 8 degrees C (56%). At 8 watts of laser power a probe temperature reduction from 591 +/- 25 degrees C to 534 +/- 36 degrees C (10%) due to 5 cm/sec probe velocity was noted. Probe temperatures were reduced to 130 +/- 30 degrees C (78%) under the combined influence of 5 cm/sec probe velocity and 170 ml/min blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effects of Biocompatible Compared with Standard Peritoneal Dialysis Solutions on Peritonitis Microbiology, Treatment, and Outcomes: the balANZ Trial

Science.gov (United States)

Johnson, David W.; Brown, Fiona G.; Clarke, Margaret; Boudville, Neil; Elias, Tony J.; Foo, Marjorie W.Y.; Jones, Bernard; Kulkarni, Hemant; Langham, Robyn; Ranganathan, Dwarakanathan; Schollum, John; Suranyi, Michael G.; Tan, Seng H.; Voss, David

2012-01-01

♦ Background: A multicenter, multi-country randomized controlled trial (the balANZ study) recently reported that peritonitis rates significantly improved with the use of neutral-pH peritoneal dialysis (PD) solutions low in glucose degradation products (“biocompatible”) compared with standard solutions. The present paper reports a secondary outcome analysis of the balANZ trial with respect to peritonitis microbiology, treatment, and outcomes. ♦ Methods: Adult incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. ♦ Results: The safety population analysis for peritonitis included 91 patients in each group. The unadjusted geometric mean peritonitis rates in those groups were 0.30 [95% confidence interval (CI): 0.22 to 0.41] episodes per patient-year for the biocompatible group and 0.49 (95% CI: 0.39 to 0.62) episodes per patient-year for the control group [incidence rate ratio (IRR): 0.61; 95% CI: 0.41 to 0.90; p = 0.01]. When specific causative organisms were examined, the rates of culture-negative, gram-positive, gram-negative, and polymicrobial peritonitis episodes were not significantly different between the biocompatible and control groups, although the biocompatible group did experience a significantly lower rate of non-pseudomonal gram-negative peritonitis (IRR: 0.41; 95% CI: 0.18 to 0.92; p = 0.03). Initial empiric antibiotic regimens were comparable between the groups. Biocompatible fluid use did not significantly reduce the risk of peritonitis-associated hospitalization (adjusted odds ratio: 0.80; 95% CI: 0.48 to 1.34), but did result in a shorter median duration of peritonitis-associated hospitalization (6 days vs 11 days, p = 0.05). Peritonitis severity was more likely to be rated as mild in the biocompatible group (37% vs 10%, p = 0.001). Overall peritonitis-associated technique failures and peritonitis-related deaths were comparable in the two groups

Evaluation of the biocompatibility of a coating material for an implantable bladder volume sensor

Directory of Open Access Journals (Sweden)

Su-Jin Kim

2012-03-01

Full Text Available As the applications for implantable medical devices have increased, the need for biocompatible packaging materials has become important. Recently, we reported an implantable sensor for real-time monitoring of the changes in bladder volume, which necessitated finding a safe coating material for use in bladder tissue. At present, materials like polyethylene glycol (PEG, polydimethylsiloxane (PDMS and parylene-C are used in biomedical devices or as coating materials, owing to their excellent safety in various medical fields. However, few studies have assessed their safety in bladder tissue, therefore, we evaluated the biocompatibility of PEG, PDMS and parylene-C in the bladder. All three materials turned out to be safe in in vitro tests of live/dead staining and cell viability. In vivo tests with hematoxylin and eosin and immunofluorescence staining with MAC387 showed no persistent inflammation. Therefore, we consider that the three materials are biocompatible in bladder tissue. Despite this safety, however, PEG has biodegradable characteristics and thus is not suitable for use as packaging. We suggest that PDMS and parylene-C can be used as safe coating materials for the implantable bladder volume sensor reported previously.

Biodegradable magnesium alloys for orthopaedic applications: A review on corrosion, biocompatibility and surface modifications.

Science.gov (United States)

Agarwal, Sankalp; Curtin, James; Duffy, Brendan; Jaiswal, Swarna

2016-11-01

Magnesium (Mg) and its alloys have been extensively explored as potential biodegradable implant materials for orthopaedic applications (e.g. Fracture fixation). However, the rapid corrosion of Mg based alloys in physiological conditions has delayed their introduction for therapeutic applications to date. The present review focuses on corrosion, biocompatibility and surface modifications of biodegradable Mg alloys for orthopaedic applications. Initially, the corrosion behaviour of Mg alloys and the effect of alloying elements on corrosion and biocompatibility is discussed. Furthermore, the influence of polymeric deposit coatings, namely sol-gel, synthetic aliphatic polyesters and natural polymers on corrosion and biological performance of Mg and its alloy for orthopaedic applications are presented. It was found that inclusion of alloying elements such as Al, Mn, Ca, Zn and rare earth elements provides improved corrosion resistance to Mg alloys. It has been also observed that sol-gel and synthetic aliphatic polyesters based coatings exhibit improved corrosion resistance as compared to natural polymers, which has higher biocompatibility due to their biomimetic nature. It is concluded that, surface modification is a promising approach to improve the performance of Mg-based biomaterials for orthopaedic applications. Copyright © 2016 Elsevier B.V. All rights reserved.

75 FR 13556 - Biocompatibles UK Ltd.; Filing of Color Additive Petition

Science.gov (United States)

2010-03-22

... filed a petition proposing that the color additive regulations be amended to provide for the safe use of...] Biocompatibles UK Ltd.; Filing of Color Additive Petition AGENCY: Food and Drug Administration, HHS. ACTION... polyvinyl alcohol as a color additive in vascular embolization devices. FOR FURTHER INFORMATION CONTACT...

Biocompatible Metal-Oxide Nanoparticles: Nanotechnology Improvement of Conventional Prosthetic Acrylic Resins

Directory of Open Access Journals (Sweden)

Laura S. Acosta-Torres

2011-01-01

Full Text Available Nowadays, most products for dental restoration are produced from acrylic resins based on heat-cured Poly(Methyl MethAcrylate (PMMA. The addition of metal nanoparticles to organic materials is known to increase the surface hydrophobicity and to reduce adherence to biomolecules. This paper describes the use of nanostructured materials, TiO2 and Fe2O3, for simultaneously coloring and/or improving the antimicrobial properties of PMMA resins. Nanoparticles of metal oxides were included during suspension polymerization to produce hybrid metal oxides-alginate-containing PMMA. Metal oxide nanoparticles were characterized by dynamic light scattering, and X-ray diffraction. Physicochemical characterization of synthesized resins was assessed by a combination of spectroscopy, scanning electron microscopy, viscometry, porosity, and mechanical tests. Adherence of Candida albicans cells and cellular compatibility assays were performed to explore biocompatibility and microbial adhesion of standard and novel materials. Our results show that introduction of biocompatible metal nanoparticles is a suitable means for the improvement of conventional acrylic dental resins.

Biocompatible Metal-Oxide Nanoparticles: Nanotechnology Improvement of Conventional Prosthetic Acrylic Resins

International Nuclear Information System (INIS)

Acosta-Torres, L.S.; Lopez-Marin, L.M.; Padron, G.H.; Castano, V.M.; Nunez-Anita, R.E.

2011-01-01

Nowadays, most products for dental restoration are produced from acrylic resins based on heat-cured Poly(Methyl Methacrylate) (PMMA). The addition of metal nanoparticles to organic materials is known to increase the surface hydrophobicity and to reduce adherence to biomolecules. This paper describes the use of nano structured materials, TiO 2 and Fe 2 O 3 , for simultaneously coloring and/or improving the antimicrobial properties of PMMA resins. Nanoparticles of metal oxides were included during suspension polymerization to produce hybrid metal oxides-alginate-containing PMMA. Metal oxide nanoparticles were characterized by dynamic light scattering, and X-ray diffraction. Physicochemical characterization of synthesized resins was assessed by a combination of spectroscopy, scanning electron microscopy, viscometry, porosity, and mechanical tests. Adherence of Candida albicans cells and cellular compatibility assays were performed to explore biocompatibility and microbial adhesion of standard and novel materials. Our results show that introduction of biocompatible metal nanoparticles is a suitable means for the improvement of conventional acrylic dental resins.

Corrosion assessment and enhanced biocompatibility analysis of biodegradable magnesium-based alloys

Science.gov (United States)

Pompa, Luis Enrique

Magnesium alloys have raised immense interest to many researchers because of its evolution as a new third generation material. Due to their biocompatibility, density, and mechanical properties, magnesium alloys are frequently reported as prospective biodegradable implant materials. Moreover, magnesium based alloys experience a natural phenomena to biodegrade in aqueous solutions due to its corrosive activity, which is excellent for orthopedic and cardiovascular applications. However, major concerns with such alloys are fast and non-uniform corrosion degradation. Controlling the degradation rate in the physiological environment determines the success of an implant. In this investigation, three grades of magnesium alloys: AZ31B, AZ91E and ZK60A were studied for their corrosion resistance and biocompatibility. Scanning electron microscopy, energy dispersive spectroscopy, atomic force microscopy and contact angle meter are used to study surface morphology, chemistry, roughness and wettability, respectively. Additionally, the cytotoxicity of the leached metal ions was evaluated by a tetrazolium based bio-assay, MTS.

Chemical composition, radiopacity, and biocompatibility of Portland cement with bismuth oxide.

Science.gov (United States)

Hwang, Yun-Chan; Lee, Song-Hee; Hwang, In-Nam; Kang, In-Chol; Kim, Min-Seok; Kim, Sun-Hun; Son, Ho-Hyun; Oh, Won-Mann

2009-03-01

This study compared the chemical constitution, radiopacity, and biocompatibility of Portland cement containing bismuth oxide (experimental cement) with those of Portland cement and mineral trioxide aggregate (MTA). The chemical constitution of materials was determined by scanning electron microscopy and energy-dispersive X-ray analysis. The radiopacity of the materials was determined using the ISO/6876 method. The biocompatibility of the materials was tested by MTT assay and tissue reaction. The constitution of all materials was similar. However, the Portland cement and experimental cement were more irregular and had a larger particle size than MTA. The radiopacity of the experimental cement was similar to MTA. The MTT assay revealed MTA to have slightly higher cell viability than the other materials. However, there were no statistically significant differences between the materials, with the exception of MTA at 24 h. There was no significant difference in the tissue reaction between the experimental groups. These results suggest that the experimental cement may be used as a substitute for MTA.

Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres.

Science.gov (United States)

Liao, Yu-Te; Liu, Chia-Hung; Yu, Jiashing; Wu, Kevin C-W

2014-01-01

A new microsphere consisting of inorganic mesoporous silica nanoparticles (MSNs) and organic alginate (denoted as MSN@Alg) was successfully synthesized by air-dynamic atomization and applied to the intracellular drug delivery systems (DDS) of liver cancer cells with sustained release and specific targeting properties. MSN@Alg microspheres have the advantages of MSN and alginate, where MSN provides a large surface area for high drug loading and alginate provides excellent biocompatibility and COOH functionality for specific targeting. Rhodamine 6G was used as a model drug, and the sustained release behavior of the rhodamine 6G-loaded MSN@Alg microspheres can be prolonged up to 20 days. For targeting therapy, the anticancer drug doxorubicin was loaded into MSN@Alg microspheres, and the (lysine)4-tyrosine-arginine-glycine-aspartic acid (K4YRGD) peptide was functionalized onto the surface of MSN@Alg for targeting liver cancer cells, hepatocellular carcinoma (HepG2). The results of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and confocal laser scanning microscopy indicate that the MSN@Alg microspheres were successfully uptaken by HepG2 without apparent cytotoxicity. In addition, the intracellular drug delivery efficiency was greatly enhanced (ie, 3.5-fold) for the arginine-glycine-aspartic acid (RGD)-labeled, doxorubicin-loaded MSN@Alg drug delivery system compared with the non-RGD case. The synthesized MSN@Alg microspheres show great potential as drug vehicles with high biocompatibility, sustained release, and targeting features for future intracellular DDS.

[Study on biocompatibility of hydroxyapatite/high density polyethylene (HA/HDPE) nano-composites artificial ossicle].

Science.gov (United States)

Wang, Guohui; Zhu, Shaihong; Tan, Guolin; Zhou, Kechao; Huang, Suping; Zhao, Yanzhong; Li, Zhiyou; Huang, Boyun

2008-06-01

This study was aimed to evaluate the biocompatibility of Hydroxyapatite/High density polyethylene (HA/ HDPE) nano-composites artificial ossicle. The percentage of S-period cells were detected by flow cytometry after L929 cells being incubated with extraction of the HA/HDPE nano-composites; the titanium materials for clinical application served as the contrast. In addition, both materials were implanted in animals and the histopathological evaluations were conducted. There were no statistically significant differences between the two groups (P >0.05). The results demonstrated that the HA/HDPE nano-composite artificial ossicle made by our laboratory is of a good biocompatibility and clinical application outlook.

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

Mechanical properties and biocompatibility of porous titanium scaffolds for bone tissue engineering.

Science.gov (United States)

Chen, Yunhui; Frith, Jessica Ellen; Dehghan-Manshadi, Ali; Attar, Hooyar; Kent, Damon; Soro, Nicolas Dominique Mathieu; Bermingham, Michael J; Dargusch, Matthew S

2017-11-01

Synthetic scaffolds are a highly promising new approach to replace both autografts and allografts to repair and remodel damaged bone tissue. Biocompatible porous titanium scaffold was manufactured through a powder metallurgy approach. Magnesium powder was used as space holder material which was compacted with titanium powder and removed during sintering. Evaluation of the porosity and mechanical properties showed a high level of compatibility with human cortical bone. Interconnectivity between pores is higher than 95% for porosity as low as 30%. The elastic moduli are 44.2GPa, 24.7GPa and 15.4GPa for 30%, 40% and 50% porosity samples which match well to that of natural bone (4-30GPa). The yield strengths for 30% and 40% porosity samples of 221.7MPa and 117MPa are superior to that of human cortical bone (130-180MPa). In-vitro cell culture tests on the scaffold samples using Human Mesenchymal Stem Cells (hMSCs) demonstrated their biocompatibility and indicated osseointegration potential. The scaffolds allowed cells to adhere and spread both on the surface and inside the pore structures. With increasing levels of porosity/interconnectivity, improved cell proliferation is obtained within the pores. It is concluded that samples with 30% porosity exhibit the best biocompatibility. The results suggest that porous titanium scaffolds generated using this manufacturing route have excellent potential for hard tissue engineering applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biocompatibility effects of biologically synthesized graphene in primary mouse embryonic fibroblast cells

Science.gov (United States)

Gurunathan, Sangiliyandi; Han, Jae Woong; Eppakayala, Vasuki; Dayem, Ahmed Abdal; Kwon, Deug-Nam; Kim, Jin-Hoi

2013-09-01

Due to unique properties and unlimited possible applications, graphene has attracted abundant interest in the areas of nanobiotechnology. Recently, much work has focused on the synthesis and properties of graphene. Here we show that a successful reduction of graphene oxide (GO) using spinach leaf extract (SLE) as a simultaneous reducing and stabilizing agent. The as-prepared SLE-reduced graphene oxide (S-rGO) was characterized by ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy. Dynamic light scattering technique was used to determine the average size of GO and S-rGO. Scanning electron microscopy and atomic force microscopy images provide clear surface morphological evidence for the formation of graphene. The resulting S-rGO has a mostly single-layer structure, is stable, and has significant water solubility. In addition, the biocompatibility of graphene was investigated using cell viability, leakage of lactate dehydrogenase and alkaline phosphatase activity in primary mouse embryonic fibroblast (PMEFs) cells. The results suggest that the biologically synthesized graphene has significant biocompatibility with PMEF cells, even at a higher concentration of 100 μg/mL. This method uses a `green', natural reductant and is free of additional stabilizing reagents; therefore, it is an environmentally friendly, simple, and cost-effective method for the fabrication of soluble graphene. This study could open up a promising view for substitution of hydrazine by a safe, biocompatible, and powerful reduction for the efficient deoxygenation of GO, especially in large-scale production and potential biomedical applications.

Mismatch discrimination of lipidated DNA and LNA-probes (LiNAs) in hybridization-controlled liposome assembly

DEFF Research Database (Denmark)

Jakobsen, Ulla; Vogel, Stefan

2016-01-01

Assays for mismatch discrimination and detection of single nucleotide variations by hybridization-controlled assembly of liposomes, which do not require tedious surface chemistry, are versatile for both DNA and RNA targets. We report herein a comprehensive study on different DNA and LNA (locked...... assay in the context of mismatch discrimination and SNP detection are presented. The advantages of membrane-anchored LiNA-probes compared to chemically attached probes on solid nanoparticles (e.g. gold nanoparticles) are described. Key functionalities such as non-covalent attachment of LiNA probes...... without the need for long spacers and the inherent mobility of membrane-anchored probes in lipid-bilayer membranes will be described for several different probe designs....

Development of a discriminatory biocompatibility testing model for non-precious dental casting alloys.

LENUS (Irish Health Repository)

McGinley, Emma Louise

2011-12-01

To develop an enhanced, reproducible and discriminatory biocompatibility testing model for non-precious dental casting alloys, prepared to a clinically relevant surface finishing condition, using TR146 oral keratinocyte cells.

In vivo evaluation of the biocompatibility of surface modified hemodialysis polysulfone hollow fibers in rat.

Directory of Open Access Journals (Sweden)

Ganpat J Dahe

Full Text Available Polysulfone (Psf hollow fiber membranes (HFMs have been widely used in blood purification but their biocompatibility remains a concern. To enhance their biocompatibility, Psf/TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate composite HFMs and 2-methacryloyloxyethyl phosphorylcholine (MPC coated Psf HFMs have been prepared. They have been evaluated for in vivo biocompatibility and graft acceptance and compared with sham and commercial membranes by intra-peritoneal implantation in rats at day 7 and 21. Normal body weights, tissue formation and angiogenesis indicate acceptance of implants by the animals. Hematological observations show presence of post-surgical stress which subsides over time. Serum biochemistry results reveal normal organ function and elevated liver ALP levels at day 21. Histological studies exhibit fibroblast recruitment cells, angiogenesis and collagen deposition at the implant surface indicating new tissue formation. Immuno-histochemistry studies show non-activation of MHC molecules signifying biocompatibilty. Additionally, Psf/TPGS exhibit most favorable tissue response as compared with other HFMs making them the material of choice for HFM preparation for hemodialysis applications.

Enhanced corrosion resistance and biocompatibility of AZ31 Mg alloy using PCL/ZnO NPs via electrospinning

Energy Technology Data Exchange (ETDEWEB)

Kim, Jinwoo [Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Mousa, Hamouda M. [Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Department of Engineering Materials and Mechanical Design, Faculty of Engineering, South Valley University, Qena 83523 (Egypt); Park, Chan Hee, E-mail: biochan@jbnu.ac.kr [Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Division of Mechanical Design Engineering, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Kim, Cheol Sang, E-mail: chskim@jbnu.ac.kr [Department of Bionanosystem Engineering, Graduate School, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Division of Mechanical Design Engineering, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of)

2017-02-28

Highlights: • PCL/ZnO composite coating layer by electrospinning techniques showed the nano-scaled and porous surface structure. • Addition of zinc oxide NPs in the PCL fibers led to enhanced coating adhesion and corrosion resistance. • The composite coated surfaces on Mg substrates improved cell attachment and proliferation. - Abstract: In the efforts to improve corrosion resistance and biocompatibility of magnesium alloys, polycarprolactone (PCL) and zinc oxide nanoparticles (ZnO NPs) composite coatings were applied onto AZ31 Mg alloys via electrospinning technique in this study. The PCL/ZnO composite coatings on Mg alloys were characterized by using FE-SEM, EDX, XPS, and FT-IR. Moreover, coating adhesion test, electrochemical corrosion test, and biocompatibility test in vitro were performed to measure coating performance. Our results revealed that the increase in the content of ZnO NPs in the composite coatings not only improved the coating adhesion of composite coatings on Mg alloys, but also increased the corrosion resistance. Furthermore, the biocompatibility of MC3T3-E1 osteoblasts of the PCL/ZnO composite coated samples was superior to the biocompatibility of the bare samples. Such data suggest that applying PCL/ZnO composite coating to the magnesium alloys has suitable potential in biomedical applications.

Enhanced corrosion resistance and biocompatibility of AZ31 Mg alloy using PCL/ZnO NPs via electrospinning

International Nuclear Information System (INIS)

Kim, Jinwoo; Mousa, Hamouda M.; Park, Chan Hee; Kim, Cheol Sang

2017-01-01

Highlights: • PCL/ZnO composite coating layer by electrospinning techniques showed the nano-scaled and porous surface structure. • Addition of zinc oxide NPs in the PCL fibers led to enhanced coating adhesion and corrosion resistance. • The composite coated surfaces on Mg substrates improved cell attachment and proliferation. - Abstract: In the efforts to improve corrosion resistance and biocompatibility of magnesium alloys, polycarprolactone (PCL) and zinc oxide nanoparticles (ZnO NPs) composite coatings were applied onto AZ31 Mg alloys via electrospinning technique in this study. The PCL/ZnO composite coatings on Mg alloys were characterized by using FE-SEM, EDX, XPS, and FT-IR. Moreover, coating adhesion test, electrochemical corrosion test, and biocompatibility test in vitro were performed to measure coating performance. Our results revealed that the increase in the content of ZnO NPs in the composite coatings not only improved the coating adhesion of composite coatings on Mg alloys, but also increased the corrosion resistance. Furthermore, the biocompatibility of MC3T3-E1 osteoblasts of the PCL/ZnO composite coated samples was superior to the biocompatibility of the bare samples. Such data suggest that applying PCL/ZnO composite coating to the magnesium alloys has suitable potential in biomedical applications.

Sensing for intracellular thiols by water-insoluble two-photon fluorescent probe incorporating nanogel

Energy Technology Data Exchange (ETDEWEB)

Guo, Xudong; Zhang, Xin; Wang, Shuangqing; Li, Shayu [Beijing National Laboratory for Molecular Sciences, Key laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Hu, Rui, E-mail: hurui@iccas.ac.cn [Beijing National Laboratory for Molecular Sciences, Key laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Li, Yi, E-mail: yili@mail.ipc.ac.cn [Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Yang, Guoqiang, E-mail: gqyang@iccas.ac.cn [Beijing National Laboratory for Molecular Sciences, Key laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China)

2015-04-15

Highlights: • A novel “turn-on” two-photon fluorescent probe based on a π-conjugated triarylboron luminogen was designed and synthesized. • Fast, selective and sensitive detection of biothiols in 100% aqueous solution by simply loaded on a nanogel. • Single-photon and two-photon fluorescent bioimaging of biothiols in NIH/3T3 fibroblasts. - Abstract: A novel “turn-on” two-photon fluorescent probe containing a π-conjugated triarylboron luminogen and a maleimide moiety DMDP-M based on the photo-induced electron transfer (PET) mechanism for biothiol detection was designed and synthesized. By simply loading the hydrophobic DMDP-M on a cross-linked Pluronic{sup ®} F127 nanogel (CL-F127), a probing system DMDP-M/CL-F127 was established, which shows quick response, high selectivity and sensitivity to cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) in aqueous phase. The DMDP-M/CL-F127 system presented the fastest response to Cys with a rate constant of 0.56 min{sup −1}, and the detection limit to Cys was calculated to be as low as 0.18 μM. The DMDP-M/CL-F127 system has been successfully applied to the fluorescence imaging of biothiols in NIH/3T3 fibroblasts either with single-photon or two-photon excitation because of its high biocompatibility and cell-membrane permeability. The present work provides a general, simple and efficient strategy for the application of hydrophobic molecules to sensing biothiols in aqueous phase, and a novel sensing system for intracellular biothiols fitted for both single-photon and two-photon fluorescence imaging.

Quantifying the Ebbinghaus figure effect: Target size, context size, and target-context distance determine the presence and direction of the illusion.

Directory of Open Access Journals (Sweden)

Hester eKnol

2015-11-01

Full Text Available Over the last 20 years, visual illusions, like the Ebbinghaus figure, have become widespread to investigate functional segregation of the visual system. This segregation reveals itself, so it is claimed, in the insensitivity of movement to optical illusions. This claim, however, faces contradictory results (and interpretations in the literature. These contradictions may be due to methodological weaknesses in, and differences across studies, some of which may hide a lack of perceptual illusion effects. Indeed, despite the long history of research with the Ebbinghaus figure, standardized configurations to predict the illusion effect are missing. Here, we present a complete geometrical description of the Ebbinghaus figure with three target sizes compatible with Fitts’ task. Each trial consisted of a stimulus and an isolated probe. The probe was controlled by the participant’s response through a staircase procedure. The participant was asked whether the probe or target appeared bigger. The factors target size, context size, target-context distance, and a control condition resulted in a 3×3×3+3 factorial design. The results indicate that the illusion magnitude, the perceptual distinctiveness, and the response time depend on the context size, distance, and especially, target size. In 33% of the factor combinations there was no illusion effect. The illusion magnitude ranged from zero to (exceptionally ten percent of the target size. The small (or absent illusion effects on perception and its possible influence on motor tasks might have been overlooked or misinterpreted in previous studies. Our results provide a basis for the application of the Ebbinghaus figure in psychophysical and motor control studies.

Multiplex fluorescence melting curve analysis for mutation detection with dual-labeled, self-quenched probes.

Directory of Open Access Journals (Sweden)

Qiuying Huang

2011-04-01

Full Text Available Probe-based fluorescence melting curve analysis (FMCA is a powerful tool for mutation detection based on melting temperature generated by thermal denaturation of the probe-target hybrid. Nevertheless, the color multiplexing, probe design, and cross-platform compatibility remain to be limited by using existing probe chemistries. We hereby explored two dual-labeled, self-quenched probes, TaqMan and shared-stem molecular beacons, in their ability to conduct FMCA. Both probes could be directly used for FMCA and readily integrated with closed-tube amplicon hybridization under asymmetric PCR conditions. Improved flexibility of FMCA by using these probes was illustrated in three representative applications of FMCA: mutation scanning, mutation identification and mutation genotyping, all of which achieved improved color-multiplexing with easy probe design and versatile probe combination and all were validated with a large number of real clinical samples. The universal cross-platform compatibility of these probes-based FMCA was also demonstrated by a 4-color mutation genotyping assay performed on five different real-time PCR instruments. The dual-labeled, self-quenched probes offered unprecedented combined advantage of enhanced multiplexing, improved flexibility in probe design, and expanded cross-platform compatibility, which would substantially improve FMCA in mutation detection of various applications.

Combined scanning probe and light scattering characterization of multi-stage self-assembly of targeted liposome-based delivery systems

International Nuclear Information System (INIS)

Farkas, N; Dagata, J A; Yang, C; Rait, A; Pirollo, K F; Chang, E H

2011-01-01

The mean size and size distribution of a targeted nanoparticle delivery system (NDS) strongly influences the intrinsic stability and functionality of this molecular complex, affects its performance as a systemic drug delivery platform and ultimately determines its efficacy toward early detection and treatment of cancer. Since its components undergo significant reorganization during multiple stages of self-assembly, it is essential to monitor the size and stability of the complex throughout the NDS formulation in order to ensure its potency and manufacturability prior to entering clinical trials. This work combines scanning probe microscopy (SPM) and dynamic light scattering (DLS) techniques to obtain quantitative and reliable size measurements of the NDS, and to investigate how variations in the NDS formulation or self-assembly process impact the size, structure and functionality of the complex with various therapeutic and diagnostic agent payloads. These combined SPM and DLS methods, when implemented at an early stage of the NDS formulation, present a potential measurement approach to facilitate drug discovery and development, optimization and quality control during manufacturing of the NDS

Effect of structure variation of the aptamer-DNA duplex probe on the performance of displacement-based electrochemical aptamer sensors.

Science.gov (United States)

Pang, Jie; Zhang, Ziping; Jin, Haizhu

2016-03-15

Electrochemical aptamer-based (E-AB) sensors employing electrode-immobilized, redox-tagged aptamer probes have emerged as a promising platform for the sensitive and quick detection of target analytes ranging from small molecules to proteins. Signal generation in this class of sensor is linked to change in electron transfer efficiency upon binding-induced change in flexibility/conformation of the aptamer probe. Because of this signaling mechanism, signal gains of these sensors can be improved by employing a displacement-based recognition system, which links target binding with a large-scale flexibility/conformation shift from the aptamer-DNA duplex to the single-stranded DNA or the native aptamer. Despite the relatively large number of displacement-based E-AB sensor samples, little attention has been paid to the structure variation of the aptamer-DNA duplex probe. Here we detail the effects of complementary length and position of the aptamer-DNA duplex probe on the performance of a model displacement-based E-AB sensor for ATP. We find that, greater background suppression and signal gain are observed with longer complementary length of the aptamer-DNA duplex probe. However, sensor equilibration time slows monotonically with increasing complementary length; and with too many target binding sites in aptamer sequence being occupied by the complementary DNA, the aptamer-target binding does not occur and no signal gain observed. We also demonstrate that signal gain of the displacement-based E-AB sensor is strongly dependent on the complementary position of the aptamer-DNA duplex probe, with complementary position located at the electrode-attached or redox-tagged end of the duplex probe, larger background suppression and signal increase than that of the middle position are observed. These results highlight the importance of rational structure design of the aptamer-DNA duplex probe and provide new insights into the optimization of displacement-based E-AB sensors. Copyright

The influence of motivating operations on generalization probes of specific mands by children with autism.

Science.gov (United States)

Fragale, Christina L; O'Reilly, Mark F; Aguilar, Jeannie; Pierce, Nigel; Lang, Russell; Sigafoos, Jeff; Lancioni, Giulio

2012-01-01

We investigated the influence of motivating operations on the generalization of newly taught mands across settings and communication partners for 3 children with autism. Two conditions were implemented prior to generalization probes. In the first condition, participants were given access to a preferred item until they rejected the item (i.e., abolishing operation). In the second condition, the item was not available to participants prior to generalization probes (i.e., establishing operation). The effects of these conditions on the generalization of newly taught mands were evaluated in a multielement design. Results indicated differentiated responding during generalization probes in which more manding with the target mand was observed following the presession no-access condition than in the presession access condition. These results support the consideration of motivating operations when assessing generalization of target mands to various untrained contexts.

Biocompatibility of Human Auricular Chondrocytes Cultured onto a Chitosan/Polyvynil Alcohol/Epichlorohydrin-Based Hydrogel for Tissue Engineering Application

OpenAIRE

Melgarejo-Ramírez, Yaaziel; Sánchez-Sánchez, Roberto; García-Carvajal, Zaira; García-López, Julieta; Gutiérrez-Gómez, Claudia; Luna-Barcenas, Gabriel; Ibarra, Clemente; Velasquillo, Cristina

2014-01-01

Tissue engineering (TE) has become an alternative for auricular reconstruction based on the combination of cells, molecular signals and biomaterials. Scaffolds are biomaterials that provide structural support for cell attachment and subsequent tissue development. Ideally, a scaffold should have characteristics such as biocompatibility and bioactivity to adequate support cell functions. Our purpose was to evaluate biocompatibility of microtic auricular chondrocytes seeded onto a chitosan-polyv...

Development of an activity-based probe for acyl-protein thioesterases

Science.gov (United States)

Garland, Megan; Schulze, Christopher J.; Foe, Ian T.; van der Linden, Wouter A.; Child, Matthew A.

2018-01-01

Protein palmitoylation is a dynamic post-translational modification (PTM) important for cellular functions such as protein stability, trafficking, localization, and protein-protein interactions. S-palmitoylation occurs via the addition of palmitate to cysteine residues via a thioester linkage, catalyzed by palmitoyl acyl transferases (PATs), with removal of the palmitate catalyzed by acyl protein thioesterases (APTs) and palmitoyl-protein thioesterases (PPTs). Tools that target the regulators of palmitoylation–PATs, APTs and PPTs–will improve understanding of this essential PTM. Here, we describe the synthesis and application of a cell-permeable activity-based probe (ABP) that targets APTs in intact mammalian cells and the parasite Toxoplasma gondii. Using a focused library of substituted chloroisocoumarins, we identified a probe scaffold with nanomolar affinity for human APTs (HsAPT1 and HsAPT2) and synthesized a fluorescent ABP, JCP174-BODIPY TMR (JCP174-BT). We use JCP174-BT to profile HsAPT activity in situ in mammalian cells, to detect an APT in T. gondii (TgPPT1). We show discordance between HsAPT activity levels and total protein concentration in some cell lines, indicating that total protein levels may not be representative of APT activity in complex systems, highlighting the utility of this probe. PMID:29364904

Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application

Energy Technology Data Exchange (ETDEWEB)

Kalita, Himani, E-mail: hkalita74@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Prashanth Kumar, B.N., E-mail: prasanthkumar999@gmail.com [School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Konar, Suraj, E-mail: suraj.konar@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Tantubay, Sangeeta, E-mail: sang.chem2@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Mahto, Madhusudan Kr., E-mail: mahtomk0@gmail.com [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Mandal, Mahitosh, E-mail: mahitosh@smst.iitkgp.ernet.in [School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal 721302 (India); Pathak, Amita, E-mail: ami@chem.iitkgp.ernet.in [Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302 (India)

2016-03-01

The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~ 48 nm and 206.51 m{sup 2}/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin. - Highlights: • Biocompatible zirconium phosphate nanoparticles were synthesized by a simple sonochemical approach. • Curcumin was rapidly loaded onto the particles by the aid by hydrogen bond formation. • The curcumin loaded zirconium phosphate nanoparticles depict pH triggered drug release phenomenon. • The nanoformulated curcumin showed enhanced anti-tumor activity as compared to the native curcumin.

Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application

International Nuclear Information System (INIS)

Kalita, Himani; Prashanth Kumar, B.N.; Konar, Suraj; Tantubay, Sangeeta; Mahto, Madhusudan Kr.; Mandal, Mahitosh; Pathak, Amita

2016-01-01

The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~ 48 nm and 206.51 m"2/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin. - Highlights: • Biocompatible zirconium phosphate nanoparticles were synthesized by a simple sonochemical approach. • Curcumin was rapidly loaded onto the particles by the aid by hydrogen bond formation. • The curcumin loaded zirconium phosphate nanoparticles depict pH triggered drug release phenomenon. • The nanoformulated curcumin showed enhanced anti-tumor activity as compared to the native curcumin.

Rheological, biocompatibility and osteogenesis assessment of fish collagen scaffold for bone tissue engineering.

Science.gov (United States)

Elango, Jeevithan; Zhang, Jingyi; Bao, Bin; Palaniyandi, Krishnamoorthy; Wang, Shujun; Wenhui, Wu; Robinson, Jeya Shakila

2016-10-01

In the present investigation, an attempt was made to find an alternative to mammalian collagen with better osteogenesis ability. Three types of collagen scaffolds - collagen, collagen-chitosan (CCH), and collagen-hydroxyapatite (CHA) - were prepared from the cartilage of Blue shark and investigated for their physico-functional and mechanical properties in relation to biocompatibility and osteogenesis. CCH scaffold was superior with pH 4.5-4.9 and viscosity 9.7-10.9cP. Notably, addition of chitosan and HA (hydroxyapatite) improved the stiffness (11-23MPa) and degradation rate but lowered the water binding capacity and porosity of the scaffold. Interestingly, CCH scaffolds remained for 3days before complete in-vitro biodegradation. The decreased amount of viable T-cells and higher level of FAS/APO-1 were substantiated the biocompatibility properties of prepared collagen scaffolds. Osteogenesis study revealed that the addition of CH and HA in both fish and mammalian collagen scaffolds could efficiently promote osteoblast cell formation. The ALP activity was significantly high in CHA scaffold-treated osteoblast cells, which suggests an enhanced bone-healing process. Therefore, the present study concludes that the composite scaffolds prepared from fish collagen with higher stiffness, lower biodegradation rate, better biocompatible, and osteogenesis properties were suitable biomaterial for a bone tissue engineering application as an alternative to mammalian collagen scaffolds. Copyright © 2016 Elsevier B.V. All rights reserved.

Polybiguanide (PHMB) loaded in PLA scaffolds displaying high hydrophobic, biocompatibility and antibacterial properties

Energy Technology Data Exchange (ETDEWEB)

Llorens, Elena; Calderón, Silvia [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Valle, Luis J. del, E-mail: luis.javier.del.valle@upc.edu [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Puiggalí, Jordi [Departament d' Enginyeria Química, Universitat Politècnica de Catalunya, Av. Diagonal 647, Barcelona E-08028 (Spain); Center for Research in Nano-Engineering (CrNE), Universitat Politècnica de Catalunya, Edifici C, C/Pasqual i Vila s/n, Barcelona E-08028 (Spain)

2015-05-01

Polyhexamethylenebiguanide hydrochloride (PHMB), a low molecular weight polymer related to chlorohexidine (CHX), is a well-known antibacterial agent. In this study, polylactide (PLA) nanofibers loaded with PHMB were produced by electrospinning to obtain 3D biodegradable scaffolds with antibacterial properties. PLA fibers loaded with CHX were used as control. The electrospun fibers were studied and analyzed by SEM, FTIR, DSC and contact angle measurements. PHMB and CHX release from loaded scaffolds was evaluated, as well as their antibacterial activity and biocompatibility. The results showed that the nanofibers became smoother and their diameter smaller with increasing the amount of loaded PHMB. This feature led to an increase of both surface roughness and hydrophobicity of the scaffold. PHMB release was highly dependent on the hydrophilicity of the medium and differed from that determined for CHX. Lastly, PHMB-loaded PLA scaffolds showed antibacterial properties since they inhibited adhesion and bacterial growth, and exhibited biocompatible characteristics for the adhesion and proliferation of both fibroblast and epithelial cell lines. - Highlights: • Nanofibers of PLA-PHMB (antibacterial polymer) were prepared by electrospinning. • PHMB has hydrophilic character but the PLA-PHMB scaffolds were highly hydrophobic. • The high-hydrophobicity of the new scaffolds conditioned the release of PHMB. • The controlled release of PHMB inhibited the growth and bacterial adhesion. • PLA-PHMB scaffolds have biocompatibility with fibroblast and epithelial cells.

PEGylation of carbon nanotubes via mussel inspired chemistry: Preparation, characterization and biocompatibility evaluation

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xiaoyong; Zeng, Guangjian; Tian, Jianwen; Wan, Qing; Huang, Qiang [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wang, Ke; Zhang, Qingsong [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China); Liu, Meiying; Deng, Fengjie [Department of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031 (China); Wei, Yen, E-mail: xiaoyongzhang1980@gmail.com [Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084 (China)

2015-10-01

Graphical abstract: Water dispersible and biocompatible PEGylated carbon nanotubes were prepared via a novel mussel inspired strategy for the first time. - Highlights: • Surface modification of CNTs via bioinspired chemistry. • CNTs with high water dispersibility and excellent biocompatibility. • PEGytion of CNTs via Michael addition reaction. • Preparation of aminated PEG molecules via chain transfer polymerization. - Abstract: A novel strategy for surface modification of multi-walled carbon nanotubes (MWCNT) was developed via combination of mussel inspired chemistry and Michael addition reaction. In this procedure, pristine MWCNT were first coated with polydopamine (PDA) through self polymerization of dopamine. The PDA functionalized CNT (CNT-PDA) were further functionalized with amino-terminated polymers (polyPEGMA), which were synthesized via free radical polymerization using cysteamine hydrochloride as the chain transfer agent and poly(ethylene glycol) monomethyl ether methacylate as the monomer. The successful modification of CNT was ascertained by a series of characterization techniques including transmission electron microscopy, Fourier transform infrared spectroscopy, thermal gravimetric analysis and X-ray photoelectron spectrometry. The polymer modified CNT showed enhanced dispersibility in aqueous and organic solution. Cytotoxicity evaluation of polymers modified CNT showed that these modified CNT are biocompatible with cells. Finally, due to the universal adhesive of PDA and chain transfer free radical polymerization, this strategy developed in this work can also be extended for surface modification of many other nanomaterials with different functional polymers.

Polybiguanide (PHMB) loaded in PLA scaffolds displaying high hydrophobic, biocompatibility and antibacterial properties

International Nuclear Information System (INIS)

Llorens, Elena; Calderón, Silvia; Valle, Luis J. del; Puiggalí, Jordi

2015-01-01

Polyhexamethylenebiguanide hydrochloride (PHMB), a low molecular weight polymer related to chlorohexidine (CHX), is a well-known antibacterial agent. In this study, polylactide (PLA) nanofibers loaded with PHMB were produced by electrospinning to obtain 3D biodegradable scaffolds with antibacterial properties. PLA fibers loaded with CHX were used as control. The electrospun fibers were studied and analyzed by SEM, FTIR, DSC and contact angle measurements. PHMB and CHX release from loaded scaffolds was evaluated, as well as their antibacterial activity and biocompatibility. The results showed that the nanofibers became smoother and their diameter smaller with increasing the amount of loaded PHMB. This feature led to an increase of both surface roughness and hydrophobicity of the scaffold. PHMB release was highly dependent on the hydrophilicity of the medium and differed from that determined for CHX. Lastly, PHMB-loaded PLA scaffolds showed antibacterial properties since they inhibited adhesion and bacterial growth, and exhibited biocompatible characteristics for the adhesion and proliferation of both fibroblast and epithelial cell lines. - Highlights: • Nanofibers of PLA-PHMB (antibacterial polymer) were prepared by electrospinning. • PHMB has hydrophilic character but the PLA-PHMB scaffolds were highly hydrophobic. • The high-hydrophobicity of the new scaffolds conditioned the release of PHMB. • The controlled release of PHMB inhibited the growth and bacterial adhesion. • PLA-PHMB scaffolds have biocompatibility with fibroblast and epithelial cells

Thermodynamics of non-bridging oxigen in silica bio-compatible glass-ceramics

Czech Academy of Sciences Publication Activity Database

Koga, N.; Strnad, Z.; Šesták, Jaroslav; Strnad, J.

2003-01-01

Roč. 71, - (2003), s. 927-937 ISSN 1418-2874 R&D Projects: GA AV ČR IAA4010101 Institutional research plan: CEZ:AV0Z1010914 Keywords : bio-compatible * bone-like apatite * glass-ceramics * mimetic material * thermodynamics Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 0.598, year: 2002

Biocompatibility of Subcutaneously Implanted Plant-Derived Cellulose Biomaterials.

Science.gov (United States)

Modulevsky, Daniel J; Cuerrier, Charles M; Pelling, Andrew E

2016-01-01

There is intense interest in developing novel biomaterials which support the invasion and proliferation of living cells for potential applications in tissue engineering and regenerative medicine. Decellularization of existing tissues have formed the basis of one major approach to producing 3D scaffolds for such purposes. In this study, we utilize the native hypanthium tissue of apples and a simple preparation methodology to create implantable cellulose scaffolds. To examine biocompatibility, scaffolds were subcutaneously implanted in wild-type, immunocompetent mice (males and females; 6-9 weeks old). Following the implantation, the scaffolds were resected at 1, 4 and 8 weeks and processed for histological analysis (H&E, Masson's Trichrome, anti-CD31 and anti-CD45 antibodies). Histological analysis revealed a characteristic foreign body response to the scaffold 1 week post-implantation. However, the immune response was observed to gradually disappear by 8 weeks post-implantation. By 8 weeks, there was no immune response in the surrounding dermis tissue and active fibroblast migration within the cellulose scaffold was observed. This was concomitant with the deposition of a new collagen extracellular matrix. Furthermore, active blood vessel formation within the scaffold was observed throughout the period of study indicating the pro-angiogenic properties of the native scaffolds. Finally, while the scaffolds retain much of their original shape they do undergo a slow deformation over the 8-week length of the study. Taken together, our results demonstrate that native cellulose scaffolds are biocompatible and exhibit promising potential as a surgical biomaterial.

Silver ions-mediated conformational switch: facile design of structure-controllable nucleic acid probes.

Science.gov (United States)

Wang, Yongxiang; Li, Jishan; Wang, Hao; Jin, Jianyu; Liu, Jinhua; Wang, Kemin; Tan, Weihong; Yang, Ronghua

2010-08-01

Conformationally constraint nucleic acid probes were usually designed by forming an intramolecular duplex based on Watson-Crick hydrogen bonds. The disadvantages of these approaches are the inflexibility and instability in complex environment of the Watson-Crick-based duplex. We report that this hydrogen bonding pattern can be replaced by metal-ligation between specific metal ions and the natural bases. To demonstrate the feasibility of this principle, two linear oligonucleotides and silver ions were examined as models for DNA hybridization assay and adenosine triphosphate detection. The both nucleic acids contain target binding sequences in the middle and cytosine (C)-rich sequences at the lateral portions. The strong interaction between Ag(+) ions and cytosines forms stable C-Ag(+)-C structures, which promises the oligonucleotides to form conformationally constraint formations. In the presence of its target, interaction between the loop sequences and the target unfolds the C-Ag(+)-C structures, and the corresponding probes unfolding can be detected by a change in their fluorescence emission. We discuss the thermodynamic and kinetic opportunities that are provided by using Ag(+) ion complexes instead of traditional Watson-Crick-based duplex. In particular, the intrinsic feature of the metal-ligation motif facilitates the design of functional nucleic acids probes by independently varying the concentration of Ag(+) ions in the medium.

A novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) specifically detects CXCR4 expressing tumors.

Science.gov (United States)

Santagata, Sara; Portella, Luigi; Napolitano, Maria; Greco, Adelaide; D'Alterio, Crescenzo; Barone, Maria Vittoria; Luciano, Antonio; Gramanzini, Matteo; Auletta, Luigi; Arra, Claudio; Zannetti, Antonella; Scala, Stefania

2017-05-31

C-X-C chemokine receptor 4 (CXCR4) is over-expressed in multiple human cancers and correlates with tumor aggressiveness, poor prognosis and increased risk for distant metastases. Imaging agents for CXCR4 are thus highly desirable. We developed a novel CXCR4-targeted near-infrared (NIR) fluorescent probe (Peptide R-NIR750) conjugating the new developed CXCR4 peptidic antagonist Peptide R with the NIR fluorescent dye VivoTag-S750. Specific CXCR4 binding was obtained in cells overexpressing human CXCR4 (B16-hCXCR4 and human melanoma cells PES43), but not in CXCR4 low expressing cells (FB-1). Ex vivo evaluation demonstrated that PepR-NIR750 specifically detects B16-hCXCR4-derived subcutaneous tumors and lung metastases. Fluorescence Molecular Tomography (FMT) in vivo imaging was performed on mice carrying subcutaneous CHO and CHO-CXCR4 tumors. PepR-NIR750 accumulates only in CXCR4-positive expressing subcutaneous tumors. Additionally, an intense NIR fluorescence signal was detected in PES43-derived lung metastases of nude mice injected with PepR-NIR750 versus mice injected with VivoTag-S750. With a therapeutic intent, mice bearing PES43-derived lung metastases were treated with Peptide R. A the dramatic reduction in PES43-derived lung metastases was detected through a decrease of the PepR-NIR750 signal. PepR-NIR750 is a specific probe for non-invasive detection of human high CXCR4-expressing tumors and metastatic lesion and thus a valuable tool for cancer molecular imaging.

Label-free biosensing with functionalized nanopipette probes.

Science.gov (United States)

Umehara, Senkei; Karhanek, Miloslav; Davis, Ronald W; Pourmand, Nader

2009-03-24

Nanopipette technology can uniquely identify biomolecules such as proteins based on differences in size, shape, and electrical charge. These differences are determined by the detection of changes in ionic current as the proteins interact with the nanopipette tip coated with probe molecules. Here we show that electrostatic, biotin-streptavidin, and antibody-antigen interactions on the nanopipette tip surface affect ionic current flowing through a 50-nm pore. Highly charged polymers interacting with the glass surface modulated the rectification property of the nanopipette electrode. Affinity-based binding between the probes tethered to the surface and their target proteins caused a change in the ionic current due to a partial blockade or an altered surface charge. These findings suggest that nanopipettes functionalized with appropriate molecular recognition elements can be used as nanosensors in biomedical and biological research.

Development of PLGA-lipid nanoparticles with covalently conjugated indocyanine green as a versatile nanoplatform for tumor-targeted imaging and drug delivery

Directory of Open Access Journals (Sweden)

Xin Y

2016-11-01

Full Text Available Yu Xin, Tie Liu, Chenlong Yang Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China Abstract: We have prepared novel poly(d,l-lactide-co-glycolide (PLGA lipid nanoparticles (PNPs that covalently conjugate folic acid (FA and indocyanine green (ICG, in addition to encapsulating resveratrol (RSV (FA-RSV/ICG-PLGA-lipid NPs, abbreviated as FA-RIPNPs; these nanoparticles have been developed for simultaneous targeted delivery of anticancer drug and fluorescence imaging. The FA-RIPNPs, with an average particle size of 92.8±2.1 nm, were prepared by a facile self-assembly-and-nanoprecipitation method, and they showed excellent stability and biocompatibility characteristics. The FA-RIPNPs exhibited an RSV encapsulation efficiency of approximately 65.6%±4.7% and a maximum release ratio of 78.2%±4.1% at pH 5.0 and 37°C. Confocal fluorescence images showed that FA-RIPNPs may facilitate a high cellular uptake via FA receptor-mediated endocytosis. Furthermore, FA-RIPNPs (containing 50 µg/mL RSV induced a 81.4%±2.1% U87 cell inhibition rate via apoptosis, a value that proved to be higher than what has been shown for free RSV (53.1%±1.1%, equivalent RSV concentration. With a formulated polyethylene glycol (PEG shell around the PLGA core, FA-RIPNPs prolonged the blood circulation of both free RSV and ICG, which approximately increased 6.96- and 39.4-fold (t1/2, respectively. Regarding FA-RIPNP use as a near-infrared probe, in vivo fluorescence images indicated a highly efficient accumulation of FA-RIPNPs in the tumor tissue, which proved to be approximately 2.8- and 12.6-fold higher than the RIPNPs and free ICG, respectively. Intravenous injection of FA-RIPNPs into U87 tumor-bearing mice demonstrated the best tumor inhibition effect for all tested drugs, including free RSV and RIPNPs, with no relapse, showing high biocompatibility and with no significant systemic in vivo toxicity over the

Bioresponsive probes for molecular imaging : Concepts and in vivo applications

NARCIS (Netherlands)

van Duijnhoven, S.M.J.; Robillard, M.S.; Langereis, S.; Grüll, H.

2015-01-01

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of

Bioresponsive probes for molecular imaging: concepts and in vivo applications

NARCIS (Netherlands)

Duijnhoven, S.M. van; Robillard, M.S.; Langereis, S.; Grull, H.

2015-01-01

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of

RTV silicone rubber surface modification for cell biocompatibility by negative-ion implantation

Energy Technology Data Exchange (ETDEWEB)

Zheng, Chenlong [Key Laboratory of Beam Technology and Material Modification Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, 100875 Beijing (China); Wang, Guangfu, E-mail: 88088@bnu.edu.cn [Key Laboratory of Beam Technology and Material Modification Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, 100875 Beijing (China); Beijing Radiation Center, 100875 Beijing (China); Chu, Yingjie; Xu, Ya; Qiu, Menglin; Xu, Mi [Key Laboratory of Beam Technology and Material Modification Ministry of Education, College of Nuclear Science and Technology, Beijing Normal University, 100875 Beijing (China)

2016-03-01

Highlights: • The radiation effect has a greater influence than doping effect on the hydrophilicity of RTV SR. • The implanted ions result in a new surface atomic bonding state and morphology. • Generating hydrophilic functional groups is a reason for the improved cell biocompatibility. • The micro roughness makes the hydrophilicity should be reduced due to the lotus effect. • Cell culture demonstrates that negative-ion implantation can improve biocompatibility. - Abstract: A negative cluster ion implantation system was built on the injector of a GIC4117 tandem accelerator. Next, the system was used to study the surface modification of room temperature vulcanization silicone rubber (RTV SR) for cell biocompatibility. The water contact angle was observed to decrease from 117.6° to 99.3° as the C{sub 1}{sup −} implantation dose was increased to 1 × 10{sup 16} ions/cm{sup 2}, and the effects of C{sub 1}{sup −}, C{sub 2}{sup −} and O{sub 1}{sup −} implantation result in only small differences in the water contact angle at 3 × 10{sup 15} ions/cm{sup 2}. These findings indicate that the hydrophilicity of RTV SR improves as the dose is increased and that the radiation effect has a greater influence than the doping effect on the hydrophilicity. There are two factors influence hydrophilicity of RTV: (1) based on the XPS and ATR-FTIR results, it can be inferred that ion implantation breaks the hydrophobic functional groups (Si−CH{sub 3}, Si−O−Si, C−H) of RTV SR and generates hydrophilic functional groups (−COOH, −OH, Si−(O){sub x} (x = 3,4)). (2) SEM reveals that the implanted surface of RTV SR appears the micro roughness such as cracks and wrinkles. The hydrophilicity should be reduced due to the lotus effect (Zhou Rui et al., 2009). These two factors cancel each other out and make the C-implantation sample becomes more hydrophilic in general terms. Finally, cell culture demonstrates that negative ion-implantation is an effective method

Probing surface magnetism with ion beams

International Nuclear Information System (INIS)

Winter, H.

2007-01-01

Ion beams can be used to probe magnetic properties of surfaces by a variety of different methods. Important features of these methods are related to trajectories of atomic projectiles scattered from the surface of a solid target and to the electronic interaction mechanisms in the surface region. Both items provide under specific conditions a high sensitivity for the detection of magnetic properties in the region at the topmost layer of surface atoms. This holds in particular for scattering under planar surface channeling conditions, where under grazing impact atoms or ions are reflected specularly from the surface without penetration into the subsurface region. Two different types of methods are employed based on the detection of the spin polarization of emitted or captured electrons and on spin blocking effects for capture into atomic terms. These techniques allow one to probe the long range and short range magnetic order in the surface region

Biocompatibility of root-end filling materials: recent update

Directory of Open Access Journals (Sweden)

Payal Saxena

2013-08-01

Full Text Available The purpose of a root-end filling is to establish a seal between the root canal space and the periradicular tissues. As root-end filling materials come into contact with periradicular tissues, knowledge of the tissue response is crucial. Almost every available dental restorative material has been suggested as the root-end material of choice at a certain point in the past. This literature review on root-end filling materials will evaluate and comparatively analyse the biocompatibility and tissue response to these products, with primary focus on newly introduced materials.

Ratiometric Time-Gated Luminescence Probe for Nitric Oxide Based on an Apoferritin-Assembled Lanthanide Complex-Rhodamine Luminescence Resonance Energy Transfer System.

Science.gov (United States)

Tian, Lu; Dai, Zhichao; Liu, Xiangli; Song, Bo; Ye, Zhiqiang; Yuan, Jingli

2015-11-03

Using apoferritin (AFt) as a carrier, a novel ratiometric luminescence probe based on luminescence resonance energy transfer (LRET) between a Tb(3+) complex (PTTA-Tb(3+)) and a rhodamine derivative (Rh-NO), PTTA-Tb(3+)@AFt-Rh-NO, has been designed and prepared for the specific recognition and time-gated luminescence detection of nitric oxide (NO) in living samples. In this LRET probe, PTTA-Tb(3+) encapsulated in the core of AFt is the energy donor, and Rh-NO, a NO-responsive rhodamine derivative, bound on the surface of AFt is the energy acceptor. The probe only emits strong Tb(3+) luminescence because the emission of rhodamine is switched off in the absence of NO. Upon reaction with NO, accompanied by the turn-on of rhodamine emission, the LRET from Tb(3+) complex to rhodamine occurs, which results in the remarkable increase and decrease of the long-lived emissions of rhodamine and PTTA-Tb(3+), respectively. After the reaction, the intensity ratio of rhodamine emission to Tb(3+) emission, I565/I539, is ∼24.5-fold increased, and the dose-dependent enhancement of I565/I539 shows a good linearity in a wide concentration range of NO. This unique luminescence response allowed PTTA-Tb(3+)@AFt-Rh-NO to be conveniently used as a ratiometric probe for the time-gated luminescence detection of NO with I565/I539 as a signal. Taking advantages of high specificity and sensitivity of the probe as well as its good water-solubility, biocompatibility, and cell membrane permeability, PTTA-Tb(3+)@AFt-Rh-NO was successfully used for the luminescent imaging of NO in living cells and Daphnia magna. The results demonstrated the efficacy of the probe and highlighted it's advantages for the ratiometric time-gated luminescence bioimaging application.

Zwitterionic Nanofibers of Super-Glue for Transparent and Biocompatible Multi-Purpose Coatings

Science.gov (United States)

Mele, Elisa; Heredia-Guerrero, José A.; Bayer, Ilker S.; Ciofani, Gianni; Genchi, Giada G.; Ceseracciu, Luca; Davis, Alexander; Papadopoulou, Evie L.; Barthel, Markus J.; Marini, Lara; Ruffilli, Roberta; Athanassiou, Athanassia

2015-09-01

Here we show that macrozwitterions of poly(ethyl 2-cyanoacrylate), commonly called Super Glue, can easily assemble into long and well defined fibers by electrospinning. The resulting fibrous networks are thermally treated on glass in order to create transparent coatings whose superficial morphology recalls the organization of the initial electrospun mats. These textured coatings are characterized by low liquid adhesion and anti-staining performance. Furthermore, the low friction coefficient and excellent scratch resistance make them attractive as solid lubricants. The inherent texture of the coatings positively affects their biocompatibility. In fact, they are able to promote the proliferation and differentiation of myoblast stem cells. Optically-transparent and biocompatible coatings that simultaneously possess characteristics of low water contact angle hysteresis, low friction and mechanical robustness can find application in a wide range of technological sectors, from the construction and automotive industries to electronic and biomedical devices.

Mechanical performance of a biocompatible biocide soda-lime glass-ceramic.

Science.gov (United States)

López-Esteban, S; Bartolomé, J F; Dí Az, L A; Esteban-Tejeda, L; Prado, C; López-Piriz, R; Torrecillas, R; Moya, J S

2014-06-01

A biocompatible soda-lime glass-ceramic in the SiO2-Na2O-Al2O3-CaO-B2O3 system containing combeite and nepheline as crystalline phases, has been obtained at 750°C by two different routes: (i) pressureless sintering and (ii) Spark Plasma Sintering. The SPS glass-ceramic showed a bending strength, Weibull modulus, and toughness similar values to the cortical human bone. This material had a fatigue limit slightly superior to cortical bone and at least two times higher than commercial dental glass-ceramics and dentine. The in vitro studies indicate that soda-lime glass-ceramic is fully biocompatible. The in vivo studies in beagle jaws showed that implanted SPS rods presented no inflammatory changes in soft tissues surrounding implants in any of the 10 different cases after four months implantation. The radiological analysis indicates no signs of osseointegration lack around implants. Moreover, the biocide activity of SPS glass-ceramic versus Escherichia coli, was found to be >4log indicating that it prevents implant infections. Because of this, the SPS new glass-ceramic is particularly promising for dental applications (inlay, crowns, etc). Copyright © 2014 Elsevier Ltd. All rights reserved.

Folic acid-targeted magnetic Tb-doped CeF3 fluorescent nanoparticles as bimodal probes for cellular fluorescence and magnetic resonance imaging.

Science.gov (United States)

Ma, Zhi-Ya; Liu, Yu-Ping; Bai, Ling-Yu; An, Jie; Zhang, Lin; Xuan, Yang; Zhang, Xiao-Shuai; Zhao, Yuan-Di

2015-10-07

Magnetic fluorescent nanoparticles (NPs) have great potential applications for diagnostics, imaging and therapy. We developed a facile polyol method to synthesize multifunctional Fe3O4@CeF3:Tb@CeF3 NPs with small size (CA) to obtain carboxyl-functionalized NPs (Fe3O4@CeF3:Tb@CeF3-COOH). Folic acid (FA) as an affinity ligand was then covalently conjugated onto NPs to yield Fe3O4@CeF3:Tb@CeF3-FA NPs. They were then applied as multimodal imaging agents for simultaneous in vitro targeted fluorescence imaging and magnetic resonance imaging (MRI) of HeLa cells with overexpressed folate receptors (FR). The results indicated that these NPs had strong luminescence and enhanced T2-weighted MR contrast and would be promising candidates as multimodal probes for both fluorescence and MRI imaging.

Identification of Cell Surface Targets through Meta-analysis of Microarray Data

Directory of Open Access Journals (Sweden)

Henry Haeberle

2012-07-01

Full Text Available High-resolution image guidance for resection of residual tumor cells would enable more precise and complete excision for more effective treatment of cancers, such as medulloblastoma, the most common pediatric brain cancer. Numerous studies have shown that brain tumor patient outcomes correlate with the precision of resection. To enable guided resection with molecular specificity and cellular resolution, molecular probes that effectively delineate brain tumor boundaries are essential. Therefore, we developed a bioinformatics approach to analyze micro-array datasets for the identification of transcripts that encode candidate cell surface biomarkers that are highly enriched in medulloblastoma. The results identified 380 genes with greater than a two-fold increase in the expression in the medulloblastoma compared with that in the normal cerebellum. To enrich for targets with accessibility for extracellular molecular probes, we further refined this list by filtering it with gene ontology to identify genes with protein localization on, or within, the plasma membrane. To validate this meta-analysis, the top 10 candidates were evaluated with immunohistochemistry. We identified two targets, fibrillin 2 and EphA3, which specifically stain medulloblastoma. These results demonstrate a novel bioinformatics approach that successfully identified cell surface and extracellular candidate markers enriched in medulloblastoma versus adjacent cerebellum. These two proteins are high-value targets for the development of tumor-specific probes in medulloblastoma. This bioinformatics method has broad utility for the identification of accessible molecular targets in a variety of cancers and will enable probe development for guided resection.

Four-probe measurements with a three-probe scanning tunneling microscope

International Nuclear Information System (INIS)

Salomons, Mark; Martins, Bruno V. C.; Zikovsky, Janik; Wolkow, Robert A.

2014-01-01

We present an ultrahigh vacuum (UHV) three-probe scanning tunneling microscope in which each probe is capable of atomic resolution. A UHV JEOL scanning electron microscope aids in the placement of the probes on the sample. The machine also has a field ion microscope to clean, atomically image, and shape the probe tips. The machine uses bare conductive samples and tips with a homebuilt set of pliers for heating and loading. Automated feedback controlled tip-surface contacts allow for electrical stability and reproducibility while also greatly reducing tip and surface damage due to contact formation. The ability to register inter-tip position by imaging of a single surface feature by multiple tips is demonstrated. Four-probe material characterization is achieved by deploying two tips as fixed current probes and the third tip as a movable voltage probe

Four-probe measurements with a three-probe scanning tunneling microscope

Energy Technology Data Exchange (ETDEWEB)

Salomons, Mark [National Institute for Nanotechnology, National Research Council of Canada, Edmonton, Alberta T6G 2M9 (Canada); Martins, Bruno V. C.; Zikovsky, Janik; Wolkow, Robert A., E-mail: rwolkow@ualberta.ca [National Institute for Nanotechnology, National Research Council of Canada, Edmonton, Alberta T6G 2M9 (Canada); Department of Physics, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada)

2014-04-15

We present an ultrahigh vacuum (UHV) three-probe scanning tunneling microscope in which each probe is capable of atomic resolution. A UHV JEOL scanning electron microscope aids in the placement of the probes on the sample. The machine also has a field ion microscope to clean, atomically image, and shape the probe tips. The machine uses bare conductive samples and tips with a homebuilt set of pliers for heating and loading. Automated feedback controlled tip-surface contacts allow for electrical stability and reproducibility while also greatly reducing tip and surface damage due to contact formation. The ability to register inter-tip position by imaging of a single surface feature by multiple tips is demonstrated. Four-probe material characterization is achieved by deploying two tips as fixed current probes and the third tip as a movable voltage probe.

Four-probe measurements with a three-probe scanning tunneling microscope.

Science.gov (United States)

Salomons, Mark; Martins, Bruno V C; Zikovsky, Janik; Wolkow, Robert A

2014-04-01

We present an ultrahigh vacuum (UHV) three-probe scanning tunneling microscope in which each probe is capable of atomic resolution. A UHV JEOL scanning electron microscope aids in the placement of the probes on the sample. The machine also has a field ion microscope to clean, atomically image, and shape the probe tips. The machine uses bare conductive samples and tips with a homebuilt set of pliers for heating and loading. Automated feedback controlled tip-surface contacts allow for electrical stability and reproducibility while also greatly reducing tip and surface damage due to contact formation. The ability to register inter-tip position by imaging of a single surface feature by multiple tips is demonstrated. Four-probe material characterization is achieved by deploying two tips as fixed current probes and the third tip as a movable voltage probe.

Flexible and biocompatible high-performance solid-state micro-battery for implantable orthodontic system

KAUST Repository

Kutbee, Arwa T.; Bahabry, Rabab R.; Alamoudi, Kholod O.; Ghoneim, Mohamed T.; Cordero, Marlon D.; Almuslem, Amani S.; Gumus, Abdurrahman; Diallo, Elhadj M.; Nassar, Joanna M.; Hussain, Aftab M.; Khashab, Niveen M.; Hussain, Muhammad Mustafa

2017-01-01

To augment the quality of our life, fully compliant personalized advanced health-care electronic system is pivotal. One of the major requirements to implement such systems is a physically flexible high-performance biocompatible energy storage

Correlation between the physicochemical properties of organic solvents and their biocompatibility toward epoxide hydrolase activity in whole-cells of a yeast, Rhodotorulasp

CSIR Research Space (South Africa)

Lotter, J

2004-08-01

Full Text Available in whole-cells of the yeast Rhodotorula sp. UOFS Y-0448 was investigated. No formal correlation between solvent biocompatibility and physicochemical properties was deductible, although the introduction of hydroxyl groups increased biocompatibility. 1...

Biocompatibility and setting time of CPM-MTA and white Portland cement clinker with or without calcium sulfate.

Science.gov (United States)

Bramante, Clovis Monteiro; Kato, Marcia Magro; Assis, Gerson Francisco de; Duarte, Marco Antonio Hungaro; Bernardineli, Norberti; Moraes, Ivaldo Gomes de; Garcia, Roberto Brandão; Ordinola-Zapata, Ronald; Bramante, Alexandre Silva

2013-01-01

To evaluate the biocompatibility and the setting time of Portland cement clinker with or without 2% or 5% calcium sulfate and MTA-CPM. Twenty-four mice (Rattus norvegicus) received subcutaneously polyethylene tubes filled with Portland cement clinker with or without 2% or 5% calcium sulfate and MTA. After 15, 30 and 60 days of implantation, the animals were killed and specimens were prepared for microscopic analysis. For evaluation of the setting time, each material was analyzed using Gilmore needles weighing 113.5 g and 456.5 g, according to the ASTM specification Number C266-08 guideline. Data were analyzed by ANOVA and Tukey's test for setting time and Kruskal-Wallis and Dunn test for biocompatibility at 5% significance level. Histologic observation showed no statistically significant difference of biocompatibility (p>0.05) among the materials in the subcutaneous tissues. For the setting time, clinker without calcium sulfate showed the shortest initial and final setting times (6.18 s/21.48 s), followed by clinker with 2% calcium sulfate (9.22 s/25.33 s), clinker with 5% calcium sulfate (10.06 s/42.46 s) and MTA (15.01 s/42.46 s). All the tested materials showed biocompatibility and the calcium sulfate absence shortened the initial and final setting times of the white Portland cement clinker.

Simplified Real-Time Multiplex Detection of Loop-Mediated Isothermal Amplification Using Novel Mediator Displacement Probes with Universal Reporters.

Science.gov (United States)

Becherer, Lisa; Bakheit, Mohammed; Frischmann, Sieghard; Stinco, Silvina; Borst, Nadine; Zengerle, Roland; von Stetten, Felix

2018-04-03

A variety of real-time detection techniques for loop-mediated isothermal amplification (LAMP) based on the change in fluorescence intensity during DNA amplification enable simultaneous detection of multiple targets. However, these techniques depend on fluorogenic probes containing target-specific sequences. That complicates the adaption to different targets leading to time-consuming assay optimization. Here, we present the first universal real-time detection technique for multiplex LAMP. The novel approach allows simple assay design and is easy to implement for various targets. The innovation features a mediator displacement probe and a universal reporter. During amplification of target DNA the mediator is displaced from the mediator displacement probe. Then it hybridizes to the reporter generating a fluorescence signal. The novel mediator displacement (MD) detection was validated against state-of-the-art molecular beacon (MB) detection by means of a HIV-1 RT-LAMP: MD surpassed MB detection by accelerated probe design (MD: 10 min, MB: 3-4 h), shorter times to positive (MD 4.1 ± 0.1 min shorter than MB, n = 36), improved signal-to-noise fluorescence ratio (MD: 5.9 ± 0.4, MB: 2.7 ± 0.4; n = 15), and showed equally good or better analytical performance parameters. The usability of one universal mediator-reporter set in different multiplex assays was successfully demonstrated for a biplex RT-LAMP of HIV-1 and HTLV-1 and a biplex LAMP of Haemophilus ducreyi and Treponema pallidum, both showing good correlation between target concentration and time to positive. Due to its simple implementation it is suggested to extend the use of the universal mediator-reporter sets to the detection of various other diagnostic panels.

Targeted cancer cell death induced by biofunctionalized magnetic nanowires

KAUST Repository

Contreras, Maria F.; Ravasi, Timothy; Kosel, Jü rgen

2014-01-01

Magnetic micro and nanomaterials are increasingly interesting for biomedical applications since they possess many advantageous properties: they can become biocompatible, they can be functionalized to target specific cells and they can be remotely manipulated by magnetic fields. The goal of this study is to use antibody-functionalized nickel nanowires (Ab-NWs) as an alternative method in cancer therapy overcoming the limitations of current treatments that lack specificity and are highly cytotoxic. Ab-NWs have been incubated with cancer cells and a 12% drop on cell viability was observed for a treatment of only 10 minutes and an alternating magnetic field of low intensity and low frequency. It is believed that the Ab-NWs vibrate transmitting a mechanical force to the targeted cells inducing cell death. © 2014 IEEE.

Targeted cancer cell death induced by biofunctionalized magnetic nanowires