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Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo
Li Y, Liu J, Zhong Y, Zhang J, Wang Z, Wang L, An Y, Lin M, Gao Z, Zhang D
International Journal of Nanomedicine , 2011, DOI: http://dx.doi.org/10.2147/IJN.S24596
Abstract: iocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo Original Research (6044) Total Article Views Authors: Li Y, Liu J, Zhong Y, Zhang J, Wang Z, Wang L, An Y, Lin M, Gao Z, Zhang D Published Date November 2011 Volume 2011:6 Pages 2805 - 2819 DOI: http://dx.doi.org/10.2147/IJN.S24596 Yuntao Li1,2, Jing Liu1, Yuejiao Zhong3, Jia Zhang1, Ziyu Wang1, Li Wang1, Yanli An1, Mei Lin1, Zhiqiang Gao2, Dongsheng Zhang1 1School of Medicine, Southeast University, Nanjing, Jiangsu Province, People's Republic of China; 2Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China; 3Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, Jiangsu Province, People's Republic of China Purpose: This research was conducted to assess the biocompatibility of the core-shell Fe3O4@Au composite magnetic nanoparticles (MNPs), which have potential application in tumor hyperthermia. Methods: Fe3O4@Au composite MNPs with core-shell structure were synthesized by reduction of Au3+ in the presence of Fe3O4-MNPs prepared by improved co-precipitation. Cytotoxicity assay, hemolysis test, micronucleus (MN) assay, and detection of acute toxicity in mice and beagle dogs were then carried out. Results: The result of cytotoxicity assay showed that the toxicity grade of this material on mouse fibroblast cell line (L-929) was classified as grade 1, which belongs to no cytotoxicity. Hemolysis rates showed 0.278%, 0.232%, and 0.197%, far less than 5%, after treatment with different concentrations of Fe3O4@Au composite MNPs. In the MN assay, there was no significant difference in MN formation rates between the experimental groups and negative control (P > 0.05), but there was a significant difference between the experimental groups and the positive control (P < 0.05). The median lethal dose of the Fe3O4@Au composite MNPs after intraperitoneal administration in mice was 8.39 g/kg, and the 95% confidence interval was 6.58-10.72 g/kg, suggesting that these nanoparticles have a wide safety margin. Acute toxicity testing in beagle dogs also showed no significant difference in body weight between the treatment groups at 1, 2, 3, and 4 weeks after liver injection and no behavioral changes. Furthermore, blood parameters, autopsy, and histopathological studies in the experimental group showed no significant difference compared with the control group. Conclusion: The results indicate that Fe3O4@Au composite MNPs appear to be highly biocompatible and safe nanoparticles that are suitable for further application in tumor hyperthermia.
Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo  [cached]
Li Y,Liu J,Zhong Y,Zhang J
International Journal of Nanomedicine , 2011,
Abstract: Yuntao Li1,2, Jing Liu1, Yuejiao Zhong3, Jia Zhang1, Ziyu Wang1, Li Wang1, Yanli An1, Mei Lin1, Zhiqiang Gao2, Dongsheng Zhang11School of Medicine, Southeast University, Nanjing, Jiangsu Province, People's Republic of China; 2Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of China; 3Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research, Nanjing, Jiangsu Province, People's Republic of ChinaPurpose: This research was conducted to assess the biocompatibility of the core-shell Fe3O4@Au composite magnetic nanoparticles (MNPs), which have potential application in tumor hyperthermia. Methods: Fe3O4@Au composite MNPs with core-shell structure were synthesized by reduction of Au3+ in the presence of Fe3O4-MNPs prepared by improved co-precipitation. Cytotoxicity assay, hemolysis test, micronucleus (MN) assay, and detection of acute toxicity in mice and beagle dogs were then carried out.Results: The result of cytotoxicity assay showed that the toxicity grade of this material on mouse fibroblast cell line (L-929) was classified as grade 1, which belongs to no cytotoxicity. Hemolysis rates showed 0.278%, 0.232%, and 0.197%, far less than 5%, after treatment with different concentrations of Fe3O4@Au composite MNPs. In the MN assay, there was no significant difference in MN formation rates between the experimental groups and negative control (P > 0.05), but there was a significant difference between the experimental groups and the positive control (P < 0.05). The median lethal dose of the Fe3O4@Au composite MNPs after intraperitoneal administration in mice was 8.39 g/kg, and the 95% confidence interval was 6.58-10.72 g/kg, suggesting that these nanoparticles have a wide safety margin. Acute toxicity testing in beagle dogs also showed no significant difference in body weight between the treatment groups at 1, 2, 3, and 4 weeks after liver injection and no behavioral changes. Furthermore, blood parameters, autopsy, and histopathological studies in the experimental group showed no significant difference compared with the control group.Conclusion: The results indicate that Fe3O4@Au composite MNPs appear to be highly biocompatible and safe nanoparticles that are suitable for further application in tumor hyperthermia. Keywords: toxicity, hyperthermia, core-shell
Biocompatibility of Fe3O4/DNR magnetic nanoparticles in the treatment of hematologic malignancies
Weiwei Wu, Baoan Chen, Jian Cheng, et al
International Journal of Nanomedicine , 2010, DOI: http://dx.doi.org/10.2147/IJN.S15660
Abstract: iocompatibility of Fe3O4/DNR magnetic nanoparticles in the treatment of hematologic malignancies Original Research (5877) Total Article Views Authors: Weiwei Wu, Baoan Chen, Jian Cheng, et al Published Date December 2010 Volume 2010:5 Pages 1079 - 1084 DOI: http://dx.doi.org/10.2147/IJN.S15660 Weiwei Wu1,2, Baoan Chen1,2, Jian Cheng1, Jun Wang1,2, Wenlin Xu3, Lijie Liu4, Guohua Xia2, Hulai Wei5, Xuemei Wang6, Mingming Yang2, Liya Yang2, Yi Zhang2, Chuanlu Xu2, Jieyong Li2 1Department of Hematology, 2College of Medicine, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China; 3Department of Hematology, The First People’s Hospital of Zhenjiang, Zhenjiang, People’s Republic of China; 4Institution of Physiology, Southeast University, Nanjing; 5School of Basic Medical Science, Lanzhou University, Lanzhou, People’s Republic of China; 6State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), Southeast University, Nanjing, People’s Republic of China Purpose: The objectives of this research were to assess the biocompatibility of self-assembled Fe3O4 magnetic nanoparticles (MNPs) loaded with daunorubicin (DNR), ie, (Fe3O4-MNPs/DNR), and to explore their potential application in the treatment of hematologic malignancies. Methods: A hemolysis test was carried out to estimate the hematologic toxicity of Fe3O4-MNPs/DNR and a micronucleus assay was undertaken to identify its genotoxicity. Fe3O4-MNPs/DNR were injected intraperitoneally into mice to calculate the median lethal dose (LD50). The general condition of the mice was recorded, along with testing for acute toxicity to the liver and kidneys. Results: Hemolysis rates were 2.908%, 2.530%, and 2.415% after treatment with different concentrations of Fe3O4-MNPs/DNR. In the micronucleus assay, there was no significant difference in micronucleus formation rate between the experimental Fe3O4-MNPs/DNR groups and negative controls (P > 0.05), but there was a significant difference between the experimental groups and the positive controls (P > 0.05). The LD50 of the Fe3O4-MNPs/DNR was 1009.71 mg/kg and the 95% confidence interval (CI) was 769.11–1262.40 mg/kg, while that of the DNR groups was 8.51 mg/kg (95% CI: 6.48–10.37 mg/kg), suggesting that these nanoparticles have a wide safety margin. Acute toxicity testing showed no significant difference in body weight between the treatment groups at 24, 48, and 72 hours after intraperitoneal injection. The mice were all in good condition, with normal consumption of water and food, and their stools were formed and yellowish-brown. Interestingly, no toxic reactions, including instability of gait, convulsion, paralysis, and respiratory depression, were observed. Furthermore, alanine transaminase, blood urea nitrogen, and creatinine clearance in the experimental Fe3O4-MNPs/DNR groups were 66.0 ± 28.55 U/L, 9.06 ± 1.05 mmol/L, and 18.03 ± 1.84 μmol/L, respectively, which was not significantly different compared with the control a
Synthesis and Characterization of Silver Nanoparticles Using Cannonball Leaves and Their Cytotoxic Activity against MCF-7 Cell Line  [PDF]
Preetha Devaraj,Prachi Kumari,Chirom Aarti,Arun Renganathan
Journal of Nanotechnology , 2013, DOI: 10.1155/2013/598328
Abstract: Cannonball (Couroupita guianensis) is a tree belonging to the family Lecythidaceae. Various parts of the tree have been reported to contain oils, keto steroids, glycosides, couroupitine, indirubin, isatin, and phenolic substances. We report here the synthesis of silver nanoparticles (AgNPs) using cannonball leaves. Green synthesized nanoparticles have been characterized by UV-Vis spectroscopy, SEM, TEM, and FTIR. Cannonball leaf broth as a reducing agent converts silver ions to AgNPs in a rapid and ecofriendly manner. The UV-Vis spectra gave surface plasmon resonance peak at 434?nm. TEM image shows well-dispersed silver nanoparticles with an average particle size of 28.4?nm. FTIR showed the structure and respective bands of the synthesized nanoparticles and the stretch of bonds. Green synthesized silver nanoparticles by cannonball leaf extract show cytotoxicity to human breast cancer cell line (MCF-7). Overall, this environmentally friendly method of biological silver nanoparticles production provides rates of synthesis faster than or comparable to those of chemical methods and can potentially be used in various human contacting areas such as cosmetics, foods, and medical applications. 1. Introduction Couroupita guianensis, whose common names include ayahuma and the cannonball tree, is an evergreen tree allied to the Brazil nut (Bertholletia excelsa) and is native to tropical northern South America and to the southern Caribbean. As per textual record, the tree has been growing for the past three thousand years in India. The cannonball tree possesses many medicinal properties such as antibiotic, antifungal, antiseptic, and analgesic qualities. Extracts of this tree were used to cure colds and stomach aches. Juice made from the leaves is used to cure skin diseases and malaria. The inside of the fruit can disinfect wounds and young leaves ease toothache. The fruit emits an unpleasant odour and can be used as an insect repellent just by rubbing it to the skin or clothes [1, 2]. Overall the tree possesses skin fibroblast proliferation, antioxidant [3, 4], antihelmintic [5], wound healing, antimicrobial, and antinociceptive [1] activities. Nanotechnology is significant on account of its pre-eminence upon the comprehension, use, and control of matter at magnitudes of a minute scale, akin to approaching atomic levels, with which to manufacture new substances, instruments, and frameworks [6]. The synthesis of nanocrystals is in the limelight in modern nanotechnology. Biosynthesis of nanoparticles by plant extracts is currently under exploitation [7].
Biocompatibility of crystalline opal nanoparticles  [cached]
Hernández-Ortiz Marlen,Acosta-Torres Laura S,Hernández-Padrón Genoveva,Mendieta Alicia I
BioMedical Engineering OnLine , 2012, DOI: 10.1186/1475-925x-11-78
Abstract: Background Silica nanoparticles are being developed as a host of biomedical and biotechnological applications. For this reason, there are more studies about biocompatibility of silica with amorphous and crystalline structure. Except hydrated silica (opal), despite is presents directly and indirectly in humans. Two sizes of crystalline opal nanoparticles were investigated in this work under criteria of toxicology. Methods In particular, cytotoxic and genotoxic effects caused by opal nanoparticles (80 and 120 nm) were evaluated in cultured mouse cells via a set of bioassays, methylthiazolyldiphenyl-tetrazolium-bromide (MTT) and 5-bromo-2′-deoxyuridine (BrdU). Results 3T3-NIH cells were incubated for 24 and 72 h in contact with nanocrystalline opal particles, not presented significant statistically difference in the results of cytotoxicity. Genotoxicity tests of crystalline opal nanoparticles were performed by the BrdU assay on the same cultured cells for 24 h incubation. The reduction of BrdU-incorporated cells indicates that nanocrystalline opal exposure did not caused unrepairable damage DNA. Conclusions There is no relationship between that particles size and MTT reduction, as well as BrdU incorporation, such that the opal particles did not induce cytotoxic effect and genotoxicity in cultured mouse cells.
Biocompatibility and Toxicity of Nanoparticles and Nanotubes
Xiaoming Li,Lu Wang,Yubo Fan,Qingling Feng,Fu-zhai Cui
Journal of Nanomaterials , 2012, DOI: 10.1155/2012/548389
Abstract: In recent years, nanoparticles (NPs) have increasingly found practical applications in technology, research, and medicine. The small particle size coupled with their unique chemical and physical properties is thought to underline their exploitable biomedical activities. Its form may be latex body, polymer, ceramic particle, metal particles, and the carbon particles. Due to their small size and physical resemblance to physiological molecules such as proteins, NPs possess the capacity to revolutionise medical imaging, diagnostics, therapeutics, as well as carry out functional biological processes. But these features may also underline their toxicity. Indeed, a detailed assessment of the factors that influence the biocompatibility and toxicity of NPs is crucial for the safe and sustainable development of the emerging NPs. Due to the unique structure, size, and shape, much effort has been dedicated to analyzing biomedical applications of nanotubes.This paper focuses on the current understanding of the biocompatibility and toxicity of NPs with an emphasis on nanotubes.
Targeted Fluoromagnetic Nanoparticles for Imaging of Breast Cancer MCF-7 Cells
Mostafa Heidari Majd,Jaleh Barar,Davoud Asgari,Hadi Valizadeh
Advanced Pharmaceutical Bulletin , 2013, DOI: 10.5681/apb.2013.031
Abstract: Purpose: To achieve simultaneous imaging and therapy potentials, targeted fluoromagnetic nanoparticles were synthesized and examined in human breast cancer MCF-7 cells. Methods: Fe3O4 nanoparticles (NPs) were synthesized through thermal decomposition of Fe(acac)3. Then, magnetic nanoparticles (MNPs) modified by dopamine-poly ethylene glycol (PEG)-NH2; finally, half equivalent fluorescein isothiocyanate (FITC) and half equivalent folic acid were conjugated to one equivalent of it. The presence of Fe3O4-DPA-PEG-FA/FITC in the folate receptor (FR) positive MCF-7 cells was determined via fluorescent microscopy to monitor the cellular interaction of MNPs. Results: FT-IR spectra of final compound confirmed existence of fluorescein on folic acid grafted MNPs. The Fe3O4-DPA-PEG-FA/FITC NPs, which displayed a size rang about 30-35 nm using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), were able to actively recognize the FR-positive MCF-7 cells, but not the FR-negative A549 cells. Conclusion: The uniform nano-sized Fe3O4-DPA-PEG-FA/FITC NPs displayed great potential as theranostics and can be used for targeted imaging of various tumors that overexpress FR.
Evaluation of Hydroxyapatite Nanoparticles Biocompatibility at Different Concentrations on the Human Peripheral Blood Mononuclear Cells: An in vitro Study
Hossein Shahoon,Zahra Yadegari,Naser Valaie,Sareh Farhadi,Roya Hamedi
Research Journal of Biological Sciences , 2012, DOI: 10.3923/rjbsci.2010.764.768
Abstract: Hydroxyapatite (Ca10 (PO4)6 (OH)2) is the major inorganic component of hard tissues, the best bio-active materials which is compatible with the bone tissue. In addition, Hydroxyapatite nanoparticles (nHA) have received enormous national attention in medical and dental applications recently, the ultimate fate of the nHA within the body is still unknown. Degradation products of nanomaterials are potentially cytotoxic. Thus, it is essential to assess biocompatibility before their usage in clinical applications. The purpose of this research was to evaluate the biocompatibility of nHA on Human Peripheral Blood Mononuclear Cells (HPBMCs). To evaluation of the biocompatibility of nano-sized, rod-like hydroxyapatite particles, HPBMCs were isolated and cultured on a 96 well plate. Cells were exposed to nHA at the following: 15.5, 31.25, 62.5, 125, 250, 500, 1000, 2000, 4000 and 8000 ppm after 2, 24, 48 and 72 h later for measuring the biocompatibility of material, MTT method was utilized. Measuring the photo, absorption was done by ELISA reader system at 570 nm which assigne the vitality of cell by the value of MTT absorption cells. None of the nHA experimented concentrations were toxic so, it seems that nHA biomaterial has acceptable compatiblity with HPBMCs.
Toxicity Assessment of Silica Coated Iron Oxide Nanoparticles and Biocompatibility Improvement by Surface Engineering  [PDF]
Maria Ada Malvindi, Valeria De Matteis, Antonio Galeone, Virgilio Brunetti, George C. Anyfantis, Athanassia Athanassiou, Roberto Cingolani, Pier Paolo Pompa
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0085835
Abstract: We have studied in vitro toxicity of iron oxide nanoparticles (NPs) coated with a thin silica shell (Fe3O4/SiO2 NPs) on A549 and HeLa cells. We compared bare and surface passivated Fe3O4/SiO2 NPs to evaluate the effects of the coating on the particle stability and toxicity. NPs cytotoxicity was investigated by cell viability, membrane integrity, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) assays, and their genotoxicity by comet assay. Our results show that NPs surface passivation reduces the oxidative stress and alteration of iron homeostasis and, consequently, the overall toxicity, despite bare and passivated NPs show similar cell internalization efficiency. We found that the higher toxicity of bare NPs is due to their stronger in-situ degradation, with larger intracellular release of iron ions, as compared to surface passivated NPs. Our results indicate that surface engineering of Fe3O4/SiO2 NPs plays a key role in improving particles stability in biological environments reducing both cytotoxic and genotoxic effects.
Manufacture of IRDye800CW-coupled Fe3O4 nanoparticles and their applications in cell labeling and in vivo imaging
Yong Hou, Yingxun Liu, Zhongping Chen, Ning Gu, Jinke Wang
Journal of Nanobiotechnology , 2010, DOI: 10.1186/1477-3155-8-25
Abstract: This study manufactured 12-nm DMSA-coated Fe3O4 nanoparticles labeled with a near-infrared fluorophore, IRDye800CW (excitation/emission, 774/789 nm), to investigate their applicability in cell labeling and in vivo imaging. The mouse macrophage RAW264.7 was labeled with IRDye800CW-labeled Fe3O4 nanoparticles at concentrations of 20, 30, 40, 50, 60, 80 and 100 μg/ml for 24 h. The results revealed that the cells were efficiently labeled by the nanoparticles, without any significant effect on cell viability. The nanoparticles were injected into the mouse via the tail vein, at dosages of 2 or 5 mg/kg body weight, and the mouse was discontinuously imaged for 24 h. The results demonstrated that the nanoparticles gradually accumulated in liver and kidney regions following injection, reaching maximum concentrations at 6 h post-injection, following which they were gradually removed from these regions. After tracing the nanoparticles throughout the body it was revealed that they mainly distributed in three organs, the liver, spleen and kidney. Real-time live-body imaging effectively reported the dynamic process of the biodistribution and clearance of the nanoparticles in vivo.IRDye800CW-labeled Fe3O4 nanoparticles provide an effective probe for cell-labeling and in vivo imaging.In the past decade, the synthesis of iron-based magnetic nanoparticles has rapidly developed for fundamental biomedical applications, including bioseparation [1,2], MRI contrast enhancement [3,4], hyperthermia [5,6], and drug delivery [7,8]. For example, the Fe3O4 nanoparticle has attracted great attentions for its potential theranostic applications [9-12]. As iron nanoparticles are administered to living subjects in most of their clinical applications, their in vivo biodistribution, clearance and biocompatibility must be determined for safe clinical usage. As such, in vivo studies of iron nanoparticles have made great progress in recent years.In vivo studies of iron nanoparticles have mainly been perfo
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