Nanotoxicity of Inert Materials: The Case of Gold, Silver and Iron.

Nanotechnology has opened a new horizon of research in various fields including applied physics, chemistry, electronics, optics, robotics, biotechnology and medicine. In the biomedical field, nanomaterials have shown remarkable potential as theranostic agents. Materials which are considered inert are often used in nanomedicine owning to their nontoxic profile. At nanoscale, these inert materials have shown unique properties that differ from bulk and dissolved counterparts. In the case of metals, this unique behavior not only imparts paramount advantages but also confers toxicity due to their unwanted interaction with different cellular processes. In the literature, the toxicity of nanoparticles made from inert materials has been investigated and many of these have revealed toxic potential under specific conditions. The surge to understand underlying mechanism of toxicity has increased and different means have been employed to overcome toxicity problems associated with these agents. In this review, we have focused nanoparticles of three inert metallic materials i.e. gold, silver and iron as these are regarded as biologically inert in the bulk and dissolved form. These materials have gained wider research interest and studies indicating the toxicity of these materials are also emerging. Oxidative stress, physical binding and interference with intracellular signaling are the major role player in nanotoxicity and their predominance is highly dependent upon size, surface coating and administered dose of nanoparticles. Current strategies to overcome toxicity have also been reviewed in the light of recent literature. The authors also suggested that uniform testing standards and well-designed studies are needed to evaluate nanotoxicity of these materials that are otherwise considered as inert. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

[1]  Michael Iv,et al.  Clinical applications of iron oxide nanoparticles for magnetic resonance imaging of brain tumors. , 2015, Nanomedicine.

[2]  A. Glover,et al.  Magnetic Heating of Iron Oxide Nanoparticles and Magnetic Micelles for Cancer Therapy , 2013, IEEE Transactions on Magnetics.

[3]  Jeff W M Bulte,et al.  Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis , 2004, NMR in biomedicine.

[4]  Catherine J. Murphy,et al.  Toxicity and cellular uptake of gold nanoparticles: what we have learned so far? , 2010, Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology.

[5]  Cristina Rodríguez Padilla,et al.  Bactericidal effect of silver nanoparticles against multidrug-resistant bacteria , 2010 .

[6]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[7]  Wei-Yu Chen,et al.  Use of fluorescent DNA-templated gold/silver nanoclusters for the detection of sulfide ions. , 2011, Analytical chemistry.

[8]  Hamidreza Ghandehari,et al.  Cellular uptake and toxicity of gold nanoparticles in prostate cancer cells: a comparative study of rods and spheres , 2009, Journal of applied toxicology : JAT.

[9]  Ricardo Aurino Pinho,et al.  Effects of phonophoresis with gold nanoparticles on oxidative stress parameters in a traumatic muscle injury model , 2016, Drug delivery.

[10]  M. Thanou,et al.  Targeting nanoparticles to cancer. , 2010, Pharmacological research.

[11]  D. Mcclements,et al.  Uptake of Gold Nanoparticles by Intestinal Epithelial Cells: Impact of Particle Size on Their Absorption, Accumulation, and Toxicity. , 2015, Journal of agricultural and food chemistry.

[12]  B. Pineda,et al.  Application of Nanoparticles on Diagnosis and Therapy in Gliomas , 2013, BioMed research international.

[13]  Stella M. Marinakos,et al.  Mechanism of silver nanoparticle toxicity is dependent on dissolved silver and surface coating in Caenorhabditis elegans. , 2012, Environmental science & technology.

[14]  F. Falciani,et al.  Silver nanowire exposure results in internalization and toxicity to Daphnia magna. , 2013, ACS nano.

[15]  Yu-feng Li,et al.  Fate and toxicity of metallic and metal-containing nanoparticles for biomedical applications. , 2011, Small.

[16]  Albert Duschl,et al.  The suitability of different cellular in vitro immunotoxicity and genotoxicity methods for the analysis of nanoparticle-induced events , 2010, Nanotoxicology.

[17]  Wolfgang J. Parak,et al.  Cellular toxicity of inorganic nanoparticles: Common aspects and guidelines for improved nanotoxicity evaluation , 2011 .

[18]  D. G. Lee,et al.  Antifungal effect of silver nanoparticles on dermatophytes. , 2008, Journal of microbiology and biotechnology.

[19]  L. Que,et al.  Dioxygen activation at mononuclear nonheme iron active sites: enzymes, models, and intermediates. , 2004, Chemical reviews.

[20]  Stefan Pfuhler,et al.  Silica nanoparticles administered at the maximum tolerated dose induce genotoxic effects through an inflammatory reaction while gold nanoparticles do not. , 2012, Mutation research.

[21]  Yanhua Dong,et al.  Horseradish peroxidase functionalized fluorescent gold nanoclusters for hydrogen peroxide sensing. , 2011, Analytical chemistry.

[22]  Yuepu Pu,et al.  Evaluation on cytotoxicity and genotoxicity of the L-glutamic acid coated iron oxide nanoparticles. , 2012, Journal of nanoscience and nanotechnology.

[23]  B. Rothen‐Rutishauser,et al.  Cytotoxicity and genotoxicity of size-fractionated iron oxide (magnetite) in A549 human lung epithelial cells: role of ROS, JNK, and NF-κB. , 2011, Chemical research in toxicology.

[24]  Dong Liang,et al.  Influence of anchoring ligands and particle size on the colloidal stability and in vivo biodistribution of polyethylene glycol-coated gold nanoparticles in tumor-xenografted mice. , 2009, Biomaterials.

[25]  Raimo Hartmann,et al.  In vivo integrity of polymer-coated gold nanoparticles. , 2015, Nature nanotechnology.

[26]  S. Soenen,et al.  Addressing the problem of cationic lipid-mediated toxicity: the magnetoliposome model. , 2009, Biomaterials.

[27]  Jaebeom Lee,et al.  Subtle cytotoxicity and genotoxicity differences in superparamagnetic iron oxide nanoparticles coated with various functional groups , 2011, International journal of nanomedicine.

[28]  S. Nie,et al.  Therapeutic Nanoparticles for Drug Delivery in Cancer Types of Nanoparticles Used as Drug Delivery Systems , 2022 .

[29]  Z. Chai,et al.  Metallomics insights for in vivo studies of metal based nanomaterials. , 2013, Metallomics : integrated biometal science.

[30]  Manuela Semmler-Behnke,et al.  Supplementary information Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat , 2014 .

[31]  S. Soenen,et al.  Assessing iron oxide nanoparticle toxicity in vitro: current status and future prospects. , 2010, Nanomedicine.

[32]  Chun-yan Liu,et al.  Catalytic properties of silver nanoparticles supported on silica spheres. , 2005, The journal of physical chemistry. B.

[33]  Jin Won Hyun,et al.  Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis. , 2011, Toxicology letters.

[34]  Neus G Bastús,et al.  Peptides conjugated to gold nanoparticles induce macrophage activation. , 2009, Molecular immunology.

[35]  Minming Zhang,et al.  Toxic effects of iron oxide nanoparticles on human umbilical vein endothelial cells , 2010, International journal of nanomedicine.

[36]  Vincent M Rotello,et al.  Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. , 2004, Bioconjugate chemistry.

[37]  Kai Yang,et al.  Multimodal Imaging Guided Photothermal Therapy using Functionalized Graphene Nanosheets Anchored with Magnetic Nanoparticles , 2012, Advanced materials.

[38]  Ikram Ullah Khan,et al.  Production of nanoparticle drug delivery systems with microfluidics tools , 2015, Expert opinion on drug delivery.

[39]  B. Jarrar,et al.  Histological alterations in the liver of rats induced by different gold nanoparticle sizes, doses and exposure duration , 2012, Journal of Nanobiotechnology.

[40]  Jie Zheng,et al.  Serum protein adsorption and excretion pathways of metal nanoparticles. , 2015, Nanomedicine.

[41]  J. de Lapuente,et al.  In vitro safety toxicology data for evaluation of gold nanoparticles-chronic cytotoxicity, genotoxicity and uptake. , 2012, Journal of nanoscience and nanotechnology.

[42]  Naomi J Halas,et al.  Theranostic nanoshells: from probe design to imaging and treatment of cancer. , 2011, Accounts of chemical research.

[43]  R. Albrecht,et al.  Toxicity assessments of multisized gold and silver nanoparticles in zebrafish embryos. , 2009, Small.

[44]  Pei-Xun Liu,et al.  Toxicologic effects of gold nanoparticles in vivo by different administration routes , 2010, International journal of nanomedicine.

[45]  J. Alam,et al.  Iron oxide nanoparticle-induced oxidative stress and genotoxicity in human skin epithelial and lung epithelial cell lines. , 2013, Current pharmaceutical design.

[46]  Omid C Farokhzad,et al.  Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo , 2011, Proceedings of the National Academy of Sciences.

[47]  Miguel Larguinho,et al.  Gold and silver nanoparticles for clinical diagnostics - From genomics to proteomics. , 2012, Journal of proteomics.

[48]  Yu Cheng,et al.  Blood-brain barrier permeable gold nanoparticles: an efficient delivery platform for enhanced malignant glioma therapy and imaging. , 2014, Small.

[49]  J. Ricci,et al.  Hyperthermic intraperitoneal chemotherapy leads to an anticancer immune response via exposure of cell surface heat shock protein 90 , 2016, Oncogene.

[50]  Ha Ryong Kim,et al.  Appropriate In Vitro Methods for Genotoxicity Testing of Silver Nanoparticles , 2013, Environmental health and toxicology.

[51]  Sabine Neuss,et al.  Gold nanoparticles of diameter 1.4 nm trigger necrosis by oxidative stress and mitochondrial damage. , 2009, Small.

[52]  J. Simard,et al.  Gold nanoparticles induce apoptosis, endoplasmic reticulum stress events and cleavage of cytoskeletal proteins in human neutrophils. , 2016, Toxicology in vitro : an international journal published in association with BIBRA.

[53]  S. Glynn,et al.  Oral iron supplementation after blood donation: a randomized clinical trial. , 2015, JAMA.

[54]  Bong Hyun Chung,et al.  Acute toxicity and pharmacokinetics of 13 nm-sized PEG-coated gold nanoparticles. , 2009, Toxicology and applied pharmacology.

[55]  I. Hussain,et al.  Protein-mediated synthesis, pH-induced reversible agglomeration, toxicity and cellular interaction of silver nanoparticles. , 2013, Colloids and surfaces. B, Biointerfaces.

[56]  Sara A Love,et al.  Development of screening assays for nanoparticle toxicity assessment in human blood: preliminary studies with charged Au nanoparticles. , 2012, Nanomedicine.

[57]  C. McLaren,et al.  Hepatic iron concentration and total body iron stores in thalassemia major. , 2000, The New England journal of medicine.

[58]  M. I. Khan,et al.  Solid and liquid lipid-based binary solid lipid nanoparticles of diacerein: in vitro evaluation of sustained release, simultaneous loading of gold nanoparticles, and potential thermoresponsive behavior , 2015, International journal of nanomedicine.

[59]  Hon-Man Liu,et al.  The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells. , 2010, Toxicology and applied pharmacology.

[60]  W. Liu,et al.  Impact of silver nanoparticles on human cells: Effect of particle size , 2010, Nanotoxicology.

[61]  M. Rai,et al.  Silver nanoparticles as a new generation of antimicrobials. , 2009, Biotechnology advances.

[62]  Valtencir Zucolotto,et al.  Cyto and genotoxicity of gold nanoparticles in human hepatocellular carcinoma and peripheral blood mononuclear cells. , 2012, Toxicology letters.

[63]  A. Cuschieri,et al.  Hybrid gold-iron oxide nanoparticles as a multifunctional platform for biomedical application , 2012, Journal of Nanobiotechnology.

[64]  J. M. de la Fuente,et al.  Cell Response to Magnetic Glyconanoparticles: Does the Carbohydrate Matter? , 2007, IEEE Transactions on NanoBioscience.

[65]  Y. Hung,et al.  Assessment of the In Vivo Toxicity of Gold Nanoparticles , 2009, Nanoscale research letters.

[66]  S. Booker,et al.  Auxiliary iron-sulfur cofactors in radical SAM enzymes. , 2015, Biochimica et biophysica acta.

[67]  Rudolf Hagen,et al.  Silver nanoparticles: evaluation of DNA damage, toxicity and functional impairment in human mesenchymal stem cells. , 2011, Toxicology letters.

[68]  Matthias Epple,et al.  TOXICITY OF SILVER NANOPARTICLES INCREASES DURING STORAGE BECAUSE OF SLOW DISSOLUTION UNDER RELEASE OF SILVER IONS , 2010 .

[69]  U. Murty,et al.  Comparative study of genotoxicity and tissue distribution of nano and micron sized iron oxide in rats after acute oral treatment. , 2013, Toxicology and applied pharmacology.

[70]  Kirk G Scheckel,et al.  Surface charge-dependent toxicity of silver nanoparticles. , 2011, Environmental science & technology.

[71]  Anjan Kr Dasgupta,et al.  Cell selective response to gold nanoparticles. , 2007, Nanomedicine : nanotechnology, biology, and medicine.

[72]  Peng Zhang,et al.  Properties and applications of protein-stabilized fluorescent gold nanoclusters: short review , 2012 .

[73]  Il Je Yu,et al.  Biopersistence of silver nanoparticles in tissues from Sprague–Dawley rats , 2013, Particle and Fibre Toxicology.

[74]  Warren C W Chan,et al.  Mediating tumor targeting efficiency of nanoparticles through design. , 2009, Nano letters.

[75]  Jian Ji,et al.  Surface and size effects on cell interaction of gold nanoparticles with both phagocytic and nonphagocytic cells. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[76]  Kenneth A. Dawson,et al.  Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts , 2008, Proceedings of the National Academy of Sciences.

[77]  D. Brabazon,et al.  Silver nanoparticles and their orthopaedic applications. , 2015, The bone & joint journal.

[78]  I. Yu,et al.  Twenty-Eight-Day Oral Toxicity, Genotoxicity, and Gender-Related Tissue Distribution of Silver Nanoparticles in Sprague-Dawley Rats , 2008 .

[79]  F. Stellacci,et al.  A general mechanism for intracellular toxicity of metal-containing nanoparticles† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01234h Click here for additional data file. , 2014, Nanoscale.

[80]  Klaus Sattler,et al.  Handbook of Nanophysics : Nanoparticles and Quantum Dots , 2016 .

[81]  Timothy J Shaw,et al.  Cellular uptake and cytotoxicity of gold nanorods: molecular origin of cytotoxicity and surface effects. , 2009, Small.

[82]  Royana Singh,et al.  Targeting of diacerein loaded lipid nanoparticles to intra-articular cartilage using chondroitin sulfate as homing carrier for treatment of osteoarthritis in rats. , 2014, Nanomedicine : nanotechnology, biology, and medicine.

[83]  Nicholas A Peppas,et al.  Engineering design and molecular dynamics of mucoadhesive drug delivery systems as targeting agents. , 2009, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[84]  Ji-Ho Park,et al.  Surface chemistry of gold nanoparticles mediates their exocytosis in macrophages. , 2014, ACS nano.

[85]  Z. Gu,et al.  Superparamagnetic Iron Oxide Nanoparticles as MRI contrast agents for Non-invasive Stem Cell Labeling and Tracking , 2013, Theranostics.

[86]  B. Manshian,et al.  (Intra)cellular stability of inorganic nanoparticles: effects on cytotoxicity, particle functionality, and biomedical applications. , 2015, Chemical reviews.

[87]  M. Pileni,et al.  Collective optical properties of silver nanoparticles organized in two-dimensional superlattices , 1999 .

[88]  Sabine Neuss,et al.  Size-dependent cytotoxicity of gold nanoparticles. , 2007, Small.

[89]  Shaobing Zhou,et al.  Magnetic micelles as a potential platform for dual targeted drug delivery in cancer therapy. , 2012, International journal of pharmaceutics.

[90]  J. Jung,et al.  Twenty-Eight-Day Inhalation Toxicity Study of Silver Nanoparticles in Sprague-Dawley Rats , 2007, Inhalation toxicology.

[91]  Vincent M Rotello,et al.  Functionalized gold nanoparticles for drug delivery. , 2007, Nanomedicine.

[92]  S. Barcikowski,et al.  Toxicity of gold nanoparticles on somatic and reproductive cells. , 2012, Advances in experimental medicine and biology.

[93]  W. D. de Jong,et al.  The effect of particle size on the cytotoxicity, inflammation, developmental toxicity and genotoxicity of silver nanoparticles. , 2011, Biomaterials.

[94]  Arezou A Ghazani,et al.  Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. , 2006, Nano letters.

[95]  Sungho Jin,et al.  Nanotoxicity of iron oxide nanoparticle internalization in growing neurons. , 2007, Biomaterials.

[96]  David J. Robertson,et al.  Gum arabic as a phytochemical construct for the stabilization of gold nanoparticles: in vivo pharmacokinetics and X-ray-contrast-imaging studies. , 2007, Small.

[97]  C. Murphy,et al.  Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. , 2005, Small.

[98]  Z. Gong,et al.  Toxicity of silver nanoparticles in zebrafish models , 2008, Nanotechnology.

[99]  P. Choyke,et al.  Improving Conventional Enhanced Permeability and Retention (EPR) Effects; What Is the Appropriate Target? , 2013, Theranostics.

[100]  D. F. Barber,et al.  Development of Magnetic Nanoparticles for Cancer Gene Therapy: A Comprehensive Review , 2013 .

[101]  Q. Zeng,et al.  Inhibitation of cellular toxicity of gold nanoparticles by surface encapsulation of silica shell for hepatocarcinoma cell application. , 2014, ACS applied materials & interfaces.

[102]  Juewen Liu,et al.  Blue emitting gold nanoclusters templated by poly-cytosine DNA at low pH and poly-adenine DNA at neutral pH. , 2012, Chemical communications.

[103]  B. van Ravenzwaay,et al.  Investigation on the genotoxicity of different sizes of gold nanoparticles administered to the lungs of rats. , 2012, Mutation research.

[104]  Brian S. Hawkett,et al.  Ultrasmall superparamagnetic iron oxide nanoparticle prelabelling of human neural precursor cells. , 2014, Biomaterials.

[105]  Magdolenova Zuzana,et al.  Safety assessment of nanoparticles cytotoxicity and genotoxicity of metal nanoparticles in vitro. , 2011, Journal of biomedical nanotechnology.

[106]  C James Kirkpatrick,et al.  Size- and coating-dependent uptake of polymer-coated gold nanoparticles in primary human dermal microvascular endothelial cells. , 2012, Biomacromolecules.

[107]  L. Hightower,et al.  Cell surface expression of heat shock proteins and the immune response. , 1996, Cell stress & chaperones.

[108]  Wensheng Lu,et al.  Effects of aggregation and the surface properties of gold nanoparticles on cytotoxicity and cell growth. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[109]  M. Wendland,et al.  MRI of Tumor-Associated Macrophages with Clinically Applicable Iron Oxide Nanoparticles , 2011, Clinical Cancer Research.

[110]  M. Yacamán,et al.  The bactericidal effect of silver nanoparticles , 2005, Nanotechnology.

[111]  Samantha A. Meenach,et al.  Characterization of PEG–iron oxide hydrogel nanocomposites for dual hyperthermia and paclitaxel delivery , 2013, Journal of biomaterials science. Polymer edition.

[112]  H. Byrne,et al.  Comparison of micro- and nanoscale Fe⁺³-containing (Hematite) particles for their toxicological properties in human lung cells in vitro. , 2012, Toxicological sciences : an official journal of the Society of Toxicology.

[113]  R M Albrecht,et al.  Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. , 2001, Journal of pharmaceutical sciences.

[114]  Taeghwan Hyeon,et al.  Chemical synthesis and assembly of uniformly sized iron oxide nanoparticles for medical applications. , 2015, Accounts of chemical research.

[115]  S. Maiti,et al.  Molecular Effects of Uptake of Gold Nanoparticles in HeLa Cells , 2007, Chembiochem : a European journal of chemical biology.

[116]  S. Harris,et al.  OxLDL-targeted iron oxide nanoparticles for in vivo MRI detection of perivascular carotid collar induced atherosclerotic lesions in ApoE-deficient mice , 2012, Journal of Lipid Research.

[117]  Hiroshi Kasai,et al.  Metal nanoparticle-induced micronuclei and oxidative DNA damage in mice , 2012, Journal of clinical biochemistry and nutrition.

[118]  H. Maeda,et al.  Exploiting the enhanced permeability and retention effect for tumor targeting. , 2006, Drug discovery today.

[119]  S. Parveen,et al.  Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[120]  M. Mortimer,et al.  Toxicity of Ag, CuO and ZnO nanoparticles to selected environmentally relevant test organisms and mammalian cells in vitro: a critical review , 2013, Archives of Toxicology.

[121]  Srikanth Pilla,et al.  Gold nanoparticles with a monolayer of doxorubicin-conjugated amphiphilic block copolymer for tumor-targeted drug delivery. , 2009, Biomaterials.

[122]  R. Shukla,et al.  Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[123]  Kyunghee Choi,et al.  Silver nanoparticles induce cytotoxicity by a Trojan-horse type mechanism. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[124]  Vincent M Rotello,et al.  Efficient gene delivery vectors by tuning the surface charge density of amino acid-functionalized gold nanoparticles. , 2008, ACS nano.

[125]  Vicki Stone,et al.  An in vitro liver model - assessing oxidative stress and genotoxicity following exposure of hepatocytes to a panel of engineered nanomaterials , 2012, Particle and Fibre Toxicology.

[126]  L. Migliore,et al.  Cyto- and genotoxicity assessment of Gold nanoparticles obtained by laser ablation in A549 lung adenocarcinoma cells , 2015, Journal of Nanoparticle Research.

[127]  R. Löbenberg,et al.  Liposomal drug delivery: a versatile platform for challenging clinical applications. , 2014, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[128]  W. Wenzel,et al.  Differential hERG ion channel activity of ultrasmall gold nanoparticles , 2013, Proceedings of the National Academy of Sciences.

[129]  Toshio Matsumoto,et al.  Superparamagnetic Nanoparticle Clusters for Cancer Theranostics Combining Magnetic Resonance Imaging and Hyperthermia Treatment , 2013, Theranostics.

[130]  G. Roam,et al.  Extensive evaluations of the cytotoxic effects of gold nanoparticles. , 2013, Biochimica et biophysica acta.

[131]  M. Delano,et al.  Emerging implications of nanotechnology on cancer diagnostics and therapeutics , 2006, Cancer.

[132]  Renu Malhotra,et al.  In vivo analysis of biodegradable liposome gold nanoparticles as efficient agents for photothermal therapy of cancer. , 2015, Nano letters.

[133]  Abraham Ulman,et al.  Adverse effects of citrate/gold nanoparticles on human dermal fibroblasts. , 2006, Small.

[134]  Victor C Yang,et al.  Brain tumor targeting of magnetic nanoparticles for potential drug delivery: effect of administration route and magnetic field topography. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[135]  Dae Hong Jeong,et al.  Antimicrobial effects of silver nanoparticles. , 2007, Nanomedicine : nanotechnology, biology, and medicine.

[136]  I. Hussain,et al.  Lecithin-gold hybrid nanocarriers as efficient and pH selective vehicles for oral delivery of diacerein-In-vitro and in-vivo study. , 2016, Colloids and surfaces. B, Biointerfaces.

[137]  O. Schmid,et al.  Effects and uptake of gold nanoparticles deposited at the air-liquid interface of a human epithelial airway model. , 2010, Toxicology and applied pharmacology.

[138]  Y. Uraoka,et al.  Gold nanoparticle-induced formation of artificial protein capsids. , 2012, Nano letters.

[139]  Anant Kumar Singh,et al.  Effect of Surface Coating on the Toxicity of Silver Nanomaterials on Human Skin Keratinocytes. , 2010, Chemical physics letters.

[140]  Morteza Mahmoudi,et al.  Magnetic fluid hyperthermia: focus on superparamagnetic iron oxide nanoparticles. , 2011, Advances in colloid and interface science.

[141]  J. Meng,et al.  Anti-CXCR4 monoclonal antibody conjugated to ultrasmall superparamagnetic iron oxide nanoparticles in an application of MR molecular imaging of pancreatic cancer cell lines , 2012, Acta radiologica.

[142]  D. Griswold,et al.  Comparative pharmacology and biological effects of different gold compounds. , 1982, The Journal of rheumatology. Supplement.

[143]  V. John,et al.  Superparamagnetic iron oxide nanoparticles with variable size and an iron oxidation state as prospective imaging agents. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[144]  A. Zherdev,et al.  Toxicity of nanosilver in intragastric studies: Biodistribution and metabolic effects. , 2016, Toxicology letters.

[145]  Arunava Goswami,et al.  Comparative analysis of stability and toxicity profile of three differently capped gold nanoparticles for biomedical usage , 2012, BioMetals.

[146]  Shuk Han Cheng,et al.  Nuclear penetration of surface functionalized gold nanoparticles. , 2009, Toxicology and applied pharmacology.

[147]  M. Gomez,et al.  [Role of iron in immunity and its relation with infections]. , 1999, Archivos latinoamericanos de nutricion.

[148]  Jihyun Song,et al.  Effects of excess dietary iron and fat on glucose and lipid metabolism. , 2013, Journal of Nutritional Biochemistry.

[149]  Fabian Herzog,et al.  Exposure of silver-nanoparticles and silver-ions to lung cells in vitro at the air-liquid interface , 2013, Particle and Fibre Toxicology.

[150]  Ali Fakhimi,et al.  Synthesis and effect of silver nanoparticles on the antibacterial activity of different antibiotics against Staphylococcus aureus and Escherichia coli. , 2007, Nanomedicine : nanotechnology, biology, and medicine.

[151]  L. Qi,et al.  Facile preparation of surface-exchangeable core@shell iron oxide@gold nanoparticles for magnetic solid-phase extraction: use of gold shell as the intermediate platform for versatile adsorbents with varying self-assembled monolayers. , 2014, Analytica chimica acta.

[152]  Ruchi Yadav,et al.  Biogenic synthesis of silver nanoparticles and their synergistic effect with antibiotics: a study against gram-positive and gram-negative bacteria. , 2010, Nanomedicine : nanotechnology, biology, and medicine.

[153]  Andrew Emili,et al.  Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. , 2012, Journal of the American Chemical Society.

[154]  Min Liu,et al.  Association of Glutathione Level and Cytotoxicity of Gold Nanoparticles in Lung Cancer Cells , 2011 .

[155]  Keishiro Tomoda,et al.  Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size. , 2008, Colloids and surfaces. B, Biointerfaces.

[156]  Ajay K. Singh,et al.  Ferric pyrophosphate citrate (Triferic™) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients , 2015, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[157]  Harald Ittrich,et al.  Superparamagnetic Iron Oxide Nanoparticles in Biomedicine: Applications and Developments in Diagnostics and Therapy , 2013, Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren.

[158]  R. Arakawa,et al.  ph‐Dependent Synthesis of Pepsin‐Mediated Gold Nanoclusters with Blue Green and Red Fluorescent Emission , 2011 .

[159]  Yang Guo,et al.  Photothermal ablation of pancreatic cancer cells with hybrid iron-oxide core gold-shell nanoparticles , 2013, International journal of nanomedicine.

[160]  I. Sondi,et al.  Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria. , 2004, Journal of colloid and interface science.

[161]  V. Poon,et al.  Antimicrobial activities of silver dressings: an in vitro comparison. , 2006, Journal of medical microbiology.

[162]  Kyunghee Choi,et al.  Repeated-dose toxicity and inflammatory responses in mice by oral administration of silver nanoparticles. , 2010, Environmental toxicology and pharmacology.

[163]  S. Fisher,et al.  Desferrioxamine mesylate for managing transfusional iron overload in people with transfusion-dependent thalassaemia. , 2013, The Cochrane database of systematic reviews.

[164]  Alaaldin M. Alkilany,et al.  Colloidal stability of gold nanorod solution upon exposure to excised human skin: Effect of surface chemistry and protein adsorption. , 2016, The international journal of biochemistry & cell biology.