Assessing nanoparticle toxicity.

Nanoparticle toxicology, an emergent field, works toward establishing the hazard of nanoparticles, and therefore their potential risk, in light of the increased use and likelihood of exposure. Analytical chemists can provide an essential tool kit for the advancement of this field by exploiting expertise in sample complexity and preparation as well as method and technology development. Herein, we discuss experimental considerations for performing in vitro nanoparticle toxicity studies, with a focus on nanoparticle characterization, relevant model cell systems, and toxicity assay choices. Additionally, we present three case studies (of silver, titanium dioxide, and carbon nanotube toxicity) to highlight the important toxicological considerations of these commonly used nanoparticles.

[1]  Rose Amal,et al.  Biological impacts of TiO2 on human lung cell lines A549 and H1299: particle size distribution effects , 2011 .

[2]  N. K. Jain,et al.  Long circulating PEGylated poly(d,l-lactide-co-glycolide) nanoparticulate delivery of Docetaxel to solid tumors , 2008 .

[3]  Julie W. Fitzpatrick,et al.  Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy , 2005, Particle and Fibre Toxicology.

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

[5]  Marc Fournelle,et al.  Polymeric entrapped thiol-coated gold nanorods: cytotoxicity and suitability as molecular optoacoustic contrast agent , 2010 .

[6]  V. Hornung,et al.  Activation of the inflammasome by amorphous silica and TiO2 nanoparticles in murine dendritic cells , 2011, Nanotoxicology.

[7]  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.

[8]  K. Paknikar,et al.  Interactions of silver nanoparticles with primary mouse fibroblasts and liver cells. , 2009, Toxicology and applied pharmacology.

[9]  J. Tour,et al.  In vitro cytotoxicity of single-walled carbon nanotube/biodegradable polymer nanocomposites. , 2008, Journal of biomedical materials research. Part A.

[10]  Xian‐Zheng Zhang,et al.  Low molecular weight polyethylenimine grafted N-maleated chitosan for gene delivery: properties and in vitro transfection studies. , 2008, Biomacromolecules.

[11]  Liming Dai,et al.  DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. , 2007, Nano letters.

[12]  Pratim Biswas,et al.  Does nanoparticle activity depend upon size and crystal phase? , 2008, Nanotoxicology.

[13]  C. Mikoryak,et al.  Cytotoxicity screening of single-walled carbon nanotubes: detection and removal of cytotoxic contaminants from carboxylated carbon nanotubes. , 2011, Molecular pharmaceutics.

[14]  Jerome A Werkmeister,et al.  Carbon nanotubes in scaffolds for tissue engineering , 2009, Expert review of medical devices.

[15]  Scott C. Brown,et al.  Research strategies for safety evaluation of nanomaterials. Part VI. Characterization of nanoscale particles for toxicological evaluation. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[16]  Björn M Reinhard,et al.  Nanoparticle-induced apoptosis propagates through hydrogen-peroxide-mediated bystander killing: insights from a human intestinal epithelium in vitro model. , 2010, ACS nano.

[17]  John M. Veranth,et al.  ZnO particulate matter requires cell contact for toxicity in human colon cancer cells. , 2010, Chemical research in toxicology.

[18]  S. Iijima.  Helical microtubules of graphitic carbon , 1991, Nature.

[19]  Sandro Santucci,et al.  Effects of single and multi walled carbon nanotubes on macrophages: cyto and genotoxicity and electron microscopy. , 2011, Mutation research.

[20]  Albert Duschl,et al.  Time evolution of the nanoparticle protein corona. , 2010, ACS nano.

[21]  Sudipta Seal,et al.  Exposure to titanium dioxide nanomaterials provokes inflammation of an in vitro human immune construct. , 2009, ACS nano.

[22]  Minnamari Vippola,et al.  Genotoxicity of nanomaterials: DNA damage and micronuclei induced by carbon nanotubes and graphite nanofibres in human bronchial epithelial cells in vitro. , 2009, Toxicology letters.

[23]  Jinhee Choi,et al.  Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells. , 2008, Toxicology.

[24]  Merle G Paule,et al.  Silver nanoparticle induced blood-brain barrier inflammation and increased permeability in primary rat brain microvessel endothelial cells. , 2010, Toxicological sciences : an official journal of the Society of Toxicology.

[25]  Stephen Mann,et al.  Nanoparticles can cause DNA damage across a cellular barrier. , 2009, Nature nanotechnology.

[26]  Tim Liedl,et al.  Cytotoxicity of colloidal CdSe and CdSe/ZnS nanoparticles. , 2005, Nano letters.

[27]  M. Kreft,et al.  Toxicological aspects of long-term treatment of keratinocytes with ZnO and TiO2 nanoparticles. , 2010, Small.

[28]  C. Haynes,et al.  Stability of small mesoporous silica nanoparticles in biological media. , 2011, Chemical communications.

[29]  Liying Wang,et al.  Direct Fibrogenic Effects of Dispersed Single-Walled Carbon Nanotubes on Human Lung Fibroblasts , 2010, Journal of toxicology and environmental health. Part A.

[30]  Iseult Lynch,et al.  Reproducible comet assay of amorphous silica nanoparticles detects no genotoxicity. , 2008, Nano letters.

[31]  H. Haniu,et al.  Cellular cytotoxic response induced by highly purified multi-wall carbon nanotube in human lung cells , 2011, Molecular and Cellular Biochemistry.

[32]  Zhi Pan,et al.  Adverse effects of titanium dioxide nanoparticles on human dermal fibroblasts and how to protect cells. , 2009, Small.

[33]  D. Acosta,et al.  Predictive value of in vitro model systems in toxicology. , 1998, Annual review of pharmacology and toxicology.

[34]  Changyou Gao,et al.  Influence of silica particle internalization on adhesion and migration of human dermal fibroblasts. , 2010, Biomaterials.

[35]  Tsukasa Akasaka,et al.  Toxicity evaluations of various carbon nanomaterials. , 2011, Dental materials journal.

[36]  Taosheng Chen,et al.  Suppression of human bone morphogenetic protein signaling by carboxylated single-walled carbon nanotubes. , 2009, ACS nano.

[37]  B. Babior,et al.  The respiratory burst oxidase , 1994, Basic life sciences.

[38]  S. Shrivastava,et al.  Thrombus inducing property of atomically thin graphene oxide sheets. , 2011, ACS nano.

[39]  E. Hoek,et al.  A review of the antibacterial effects of silver nanomaterials and potential implications for human health and the environment , 2010 .

[40]  Sonja Boland,et al.  Carbon black and titanium dioxide nanoparticles elicit distinct apoptotic pathways in bronchial epithelial cells , 2010, Particle and Fibre Toxicology.

[41]  C. Haynes,et al.  Assessment of functional changes in nanoparticle-exposed neuroendocrine cells with amperometry: exploring the generalizability of nanoparticle-vesicle matrix interactions , 2010, Analytical and bioanalytical chemistry.

[42]  N. Herlin‐Boime,et al.  In vitro investigation of oxide nanoparticle and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes. , 2008, Toxicology.

[43]  Li Xiao,et al.  The effect of squalane-dissolved fullerene-C60 on adipogenesis-accompanied oxidative stress and macrophage activation in a preadipocyte-monocyte co-culture system. , 2010, Biomaterials.

[44]  Babu P. Patlolla,et al.  Evaluation of cell viability, DNA damage, and cell death in normal human dermal fibroblast cells induced by functionalized multiwalled carbon nanotube , 2010, Molecular and Cellular Biochemistry.

[45]  Yongsheng Chen,et al.  Modeling the primary size effects of citrate-coated silver nanoparticles on their ion release kinetics. , 2011, Environmental science & technology.

[46]  Patrizia Santi,et al.  Toxicity of antimony trioxide nanoparticles on human hematopoietic progenitor cells and comparison to cell lines. , 2009, Toxicology.

[47]  Rebekah Drezek,et al.  Evaluation of quantum dot cytotoxicity based on intracellular uptake. , 2006, Small.

[48]  Ivan Donati,et al.  Non-cytotoxic silver nanoparticle-polysaccharide nanocomposites with antimicrobial activity. , 2009, Biomacromolecules.

[49]  Jun Yang,et al.  Cytotoxic and genotoxic effects of multi-wall carbon nanotubes on human umbilical vein endothelial cells in vitro. , 2011, Mutation research.

[50]  K. Dawson,et al.  Characterisation of nanoparticle size and state prior to nanotoxicological studies , 2010 .

[51]  Christy L Haynes,et al.  Cytotoxicity of graphene oxide and graphene in human erythrocytes and skin fibroblasts. , 2011, ACS applied materials & interfaces.

[52]  Sarwar Beg,et al.  Advancement in carbon nanotubes: basics, biomedical applications and toxicity , 2011, The Journal of pharmacy and pharmacology.

[53]  T. Swager,et al.  Emerging Applications of Carbon Nanotubes , 2011 .

[54]  Hans Bouwmeester,et al.  Characterization of translocation of silver nanoparticles and effects on whole-genome gene expression using an in vitro intestinal epithelium coculture model. , 2011, ACS nano.

[55]  William W. Yu,et al.  The structure, composition, and dimensions of TiO2 and ZnO nanomaterials in commercial sunscreens , 2011 .

[56]  B. Meenan,et al.  Comparative in vitro cytotoxicity study of carbon nanotubes and titania nanostructures on human lung epithelial cells. , 2011, Journal of hazardous materials.

[57]  Sung Ju Cho,et al.  Quantum dot-induced cell death involves Fas upregulation and lipid peroxidation in human neuroblastoma cells , 2007, Journal of nanobiotechnology.

[58]  M. Hande,et al.  Cytotoxicity and genotoxicity of silver nanoparticles in human cells. , 2009, ACS nano.

[59]  Peter Wick,et al.  A comparison of acute and long-term effects of industrial multiwalled carbon nanotubes on human lung and immune cells in vitro. , 2011, Toxicology letters.

[60]  E. Jabbari,et al.  Cytotoxicity of Paclitaxel in Biodegradable Self-Assembled Core-Shell Poly(Lactide-Co-Glycolide Ethylene Oxide Fumarate) Nanoparticles , 2008, Pharmaceutical Research.

[61]  I. Ivanov,et al.  Quantum dots trigger immunomodulation of the NFκB pathway in human skin cells. , 2011, Molecular immunology.

[62]  R. L. Jones,et al.  Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. , 2008, The journal of physical chemistry. B.

[63]  Jonas Baltrusaitis,et al.  Induction of Inflammasome-dependent Pyroptosis by Carbon Black Nanoparticles* , 2011, The Journal of Biological Chemistry.

[64]  Mark R. Wiesner,et al.  CeO2 nanoparticles induce DNA damage towards human dermal fibroblasts in vitro , 2009 .

[65]  H. Krug,et al.  Oops they did it again! Carbon nanotubes hoax scientists in viability assays. , 2006, Nano letters.

[66]  Yanli Liu,et al.  Cellular trajectories of peptide-modified gold particle complexes: comparison of nuclear localization signals and peptide transduction domains. , 2004, Bioconjugate chemistry.

[67]  J. West,et al.  Correlating nanoscale titania structure with toxicity: a cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[68]  Arezou A Ghazani,et al.  Assessing the effect of surface chemistry on gold nanorod uptake, toxicity, and gene expression in mammalian cells. , 2008, Small.

[69]  J Fisher,et al.  The effect of nano- and micron-sized particles of cobalt-chromium alloy on human fibroblasts in vitro. , 2007, Biomaterials.

[70]  Robert M Zucker,et al.  Darkfield-Confocal Microscopy detection of nanoscale particle internalization by human lung cells , 2011, Particle and Fibre Toxicology.

[71]  Kirsten Gerloff,et al.  Cytotoxicity and oxidative DNA damage by nanoparticles in human intestinal Caco-2 cells , 2009 .

[72]  Anita Jemec,et al.  Ecotoxicity of nanosized TiO2. Review of in vivo data. , 2011, Environmental pollution.

[73]  Andrew D Maynard,et al.  The new toxicology of sophisticated materials: nanotoxicology and beyond. , 2011, Toxicological sciences : an official journal of the Society of Toxicology.

[74]  Kathleen Wallace,et al.  Proteome profiling reveals potential toxicity and detoxification pathways following exposure of BEAS‐2B cells to engineered nanoparticle titanium dioxide , 2011, Proteomics.

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

[76]  Bryce J Marquis,et al.  Investigation of noble metal nanoparticle ζ-potential effects on single-cell exocytosis function in vitro with carbon-fiber microelectrode amperometry. , 2011, The Analyst.

[77]  Christine Pohl,et al.  Inflammatory and cytotoxic responses of an alveolar-capillary coculture model to silica nanoparticles: Comparison with conventional monocultures , 2011, Particle and Fibre Toxicology.

[78]  Saber M Hussain,et al.  Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[79]  V. Castranova,et al.  Raw single-walled carbon nanotube-induced cytotoxic effects in human bronchial epithelial cells: comparison to asbestos , 2011 .

[80]  F. Rossi,et al.  Genotoxicity and morphological transformation induced by cobalt nanoparticles and cobalt chloride: an in vitro study in Balb/3T3 mouse fibroblasts. , 2009, Mutagenesis.

[81]  Jie Wu,et al.  Involvement of JNK and P53 activation in G2/M cell cycle arrest and apoptosis induced by titanium dioxide nanoparticles in neuron cells. , 2010, Toxicology letters.

[82]  H. Autrup,et al.  Cytotoxicity and genotoxicity of silver nanoparticles in the human lung cancer cell line, A549 , 2011, Archives of Toxicology.

[83]  E. Giralt,et al.  Homogeneous conjugation of peptides onto gold nanoparticles enhances macrophage response. , 2009, ACS nano.

[84]  A. Marcus,et al.  Imaging and tracking of tat peptide-conjugated quantum dots in living cells: new insights into nanoparticle uptake, intracellular transport, and vesicle shedding. , 2007, Journal of the American Chemical Society.

[85]  Wei Liu,et al.  Nano titanium dioxide induces the generation of ROS and potential damage in HaCaT cells under UVA irradiation. , 2010, Journal of nanoscience and nanotechnology.

[86]  Christy L Haynes,et al.  Impacts of mesoporous silica nanoparticle size, pore ordering, and pore integrity on hemolytic activity. , 2010, Journal of the American Chemical Society.

[87]  D. Mukhopadhyay,et al.  Pro‐angiogenic Properties of Europium(III) Hydroxide Nanorods , 2008 .

[88]  S. Daniele,et al.  Internalisation of hybrid titanium dioxide/para-amino benzoic acid nanoparticles in human dendritic cells did not induce toxicity and changes in their functions. , 2010, Toxicology letters.

[89]  Sudipta Seal,et al.  Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential. , 2007, Biomaterials.

[90]  Á. Jos,et al.  Cytotoxicity of carboxylic acid functionalized single wall carbon nanotubes on the human intestinal cell line Caco-2. , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[91]  R. Hurt,et al.  Controlled release of biologically active silver from nanosilver surfaces. , 2010, ACS nano.

[92]  Yuliang Zhao,et al.  Cytotoxicity of carbon nanomaterials: single-wall nanotube, multi-wall nanotube, and fullerene. , 2005, Environmental science & technology.

[93]  R. Hurt,et al.  Ion release kinetics and particle persistence in aqueous nano-silver colloids. , 2010, Environmental science & technology.

[94]  S. Hackenberg,et al.  Intracellular distribution, geno- and cytotoxic effects of nanosized titanium dioxide particles in the anatase crystal phase on human nasal mucosa cells. , 2010, Toxicology letters.

[95]  Ming Yan,et al.  An in vitro study of vascular endothelial toxicity of CdTe quantum dots. , 2011, Toxicology.

[96]  Jingyun Wang,et al.  Cytotoxicity of single-walled carbon nanotubes on PC12 cells. , 2011, Toxicology in vitro : an international journal published in association with BIBRA.

[97]  Timothy Thatt Yang Tan,et al.  Robust, Non‐Cytotoxic, Silica‐Coated CdSe Quantum Dots with Efficient Photoluminescence , 2005 .

[98]  J. Veranth,et al.  Cytokine responses of human lung cells (BEAS-2B) treated with micron-sized and nanoparticles of metal oxides compared to soil dusts , 2007, Particle and Fibre Toxicology.

[99]  C. Haynes,et al.  Synthesis and Characterization of Biocompatible and Size-Tunable Multifunctional Porous Silica Nanoparticles , 2009 .

[100]  Bryce J Marquis,et al.  Analytical methods to assess nanoparticle toxicity. , 2009, The Analyst.

[101]  Yong Zhang,et al.  Biocompatibility of silica coated NaYF(4) upconversion fluorescent nanocrystals. , 2008, Biomaterials.

[102]  Jinhee Choi,et al.  Oxidative stress of silica nanoparticles in human bronchial epithelial cell, Beas-2B. , 2009, Toxicology in vitro : an international journal published in association with BIBRA.

[103]  Jie Chen,et al.  Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles. , 2008, Small.

[104]  J. Loo,et al.  Adverse biophysical effects of hydroxyapatite nanoparticles on natural pulmonary surfactant. , 2011, ACS nano.

[105]  B. Ekstrand-Hammarström,et al.  Human primary bronchial epithelial cells respond differently to titanium dioxide nanoparticles than the lung epithelial cell lines A549 and BEAS-2B , 2012, Nanotoxicology.

[106]  Tung-Sheng Shih,et al.  The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. , 2008, Toxicology letters.

[107]  Vesa-Pekka Lehto,et al.  Failure of MTT as a toxicity testing agent for mesoporous silicon microparticles. , 2007, Chemical research in toxicology.

[108]  E. Testai,et al.  Toxicology investigations with cell culture systems: 20 years after. , 2004, Toxicology in vitro : an international journal published in association with BIBRA.

[109]  N. Monteiro-Riviere,et al.  Antibacterial efficacy of silver nanoparticles of different sizes, surface conditions and synthesis methods , 2011, Nanotoxicology.

[110]  John A Jansen,et al.  Carbon nanotubes in animal models: a systematic review on toxic potential. , 2011, Tissue engineering. Part B, Reviews.

[111]  Mark R Wiesner,et al.  Comparison of the abilities of ambient and manufactured nanoparticles to induce cellular toxicity according to an oxidative stress paradigm. , 2006, Nano letters.

[112]  Jeffrey I. Zink,et al.  Dispersion and stability optimization of TiO2 nanoparticles in cell culture media. , 2010, Environmental science & technology.

[113]  N. Monteiro-Riviere,et al.  Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line. , 2009, Toxicology and applied pharmacology.

[114]  N. Bottini,et al.  Multi-walled carbon nanotubes induce T lymphocyte apoptosis. , 2006, Toxicology letters.

[115]  David F. Ollis,et al.  Photoassisted heterogeneous catalysis: the degradation of trichloroethylene in water , 1983 .

[116]  Helinor Johnston,et al.  Development of in vitro systems for nanotoxicology: methodological considerations , 2009, Critical reviews in toxicology.

[117]  William W. Yu,et al.  Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes. , 2008, Toxicology and applied pharmacology.

[118]  Marie Carrière,et al.  Toxicological consequences of TiO2, SiC nanoparticles and multi-walled carbon nanotubes exposure in several mammalian cell types: an in vitro study , 2010 .

[119]  M. Hande,et al.  Anti-proliferative activity of silver nanoparticles , 2009, BMC Cell Biology.

[120]  W. Stark,et al.  The degree and kind of agglomeration affect carbon nanotube cytotoxicity. , 2007, Toxicology letters.

[121]  P. Biswas,et al.  Concept of Assessing Nanoparticle Hazards Considering Nanoparticle Dosemetric and Chemical/Biological Response Metrics , 2010, Journal of toxicology and environmental health. Part A.

[122]  Pratim Biswas,et al.  Crystal structure mediates mode of cell death in TiO2 nanotoxicity , 2009 .

[123]  Albert Duschl,et al.  Problems and challenges in the development and validation of human cell-based assays to determine nanoparticle-induced immunomodulatory effects , 2011, Particle and Fibre Toxicology.

[124]  Anil K Patri,et al.  Method for analysis of nanoparticle hemolytic properties in vitro. , 2008, Nano letters.

[125]  Alok Dhawan,et al.  Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes. , 2011, Journal of nanoscience and nanotechnology.

[126]  M. Roberts,et al.  Grey Goo on the Skin? Nanotechnology, Cosmetic and Sunscreen Safety , 2007, Critical reviews in toxicology.

[127]  A Paul Alivisatos,et al.  Cellular effect of high doses of silica-coated quantum dot profiled with high throughput gene expression analysis and high content cellomics measurements. , 2006, Nano letters.

[128]  Danielle Cleveland,et al.  Measuring silver nanoparticle dissolution in complex biological and environmental matrices using UV–visible absorbance , 2011, Analytical and bioanalytical chemistry.

[129]  Christy L. Haynes,et al.  Functional assessment of metal oxide nanoparticle toxicity in immune cells. , 2010, ACS nano.

[130]  Sophie Lanone,et al.  Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines , 2009, Particle and Fibre Toxicology.

[131]  Pratim Biswas,et al.  Validation of an LDH assay for assessing nanoparticle toxicity. , 2011, Toxicology.

[132]  Jeremy N Skepper,et al.  Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro. , 2007, Biomaterials.

[133]  Choon Nam Ong,et al.  Gold Nanoparticles Induce Oxidative Damage in Lung Fibroblasts In Vitro , 2008 .

[134]  J. Musarrat,et al.  Oxidative stress mediated apoptosis induced by nickel ferrite nanoparticles in cultured A549 cells. , 2011, Toxicology.

[135]  Paul Westerhoff,et al.  Nanoparticle silver released into water from commercially available sock fabrics. , 2008, Environmental science & technology.

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

[137]  J. Cheon,et al.  Size dependent macrophage responses and toxicological effects of Ag nanoparticles. , 2011, Chemical communications.

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

[139]  Katherine L Braun,et al.  Amperometric assessment of functional changes in nanoparticle-exposed immune cells: varying Au nanoparticle exposure time and concentration. , 2009, The Analyst.

[140]  Igor L. Medintz,et al.  Analyzing nanomaterial bioconjugates: a review of current and emerging purification and characterization techniques. , 2011, Analytical chemistry.

[141]  H. Krug,et al.  Carbon nanotubes show no sign of acute toxicity but induce intracellular reactive oxygen species in dependence on contaminants. , 2007, Toxicology letters.

[142]  Jorge Mejia,et al.  Cytotoxicity of multi-walled carbon nanotubes in three skin cellular models: Effects of sonication, dispersive agents and corneous layer of reconstructed epidermis , 2010, Nanotoxicology.

[143]  G. Adami,et al.  Silver nanoparticles exert a long-lasting antiproliferative effect on human keratinocyte HaCaT cell line. , 2011, Toxicology in vitro : an international journal published in association with BIBRA.

[144]  Deepthy Menon,et al.  Development and haematotoxicological evaluation of doped hydroxyapatite based multimodal nanocontrast agent for near-infrared, magnetic resonance and X-ray contrast imaging , 2012, Nanotoxicology.

[145]  I. Iavicoli,et al.  Toxicological effects of titanium dioxide nanoparticles: a review of in vitro mammalian studies. , 2011, European review for medical and pharmacological sciences.