The Biomechanisms of Metal and Metal-Oxide Nanoparticles’ Interactions with Cells

Humans are increasingly exposed to nanoparticles (NPs) in medicine and in industrial settings, where significant concentrations of NPs are common. However, NP interactions with and effects on biomolecules and organisms have only recently been addressed. Within we review the literature regarding proposed modes of action for metal and metal-oxide NPs, two of the most prevalent types manufactured. Iron-oxide NPs, for instance, are used as tracers for magnetic resonance imaging of oncological tumors and as vehicles for therapeutic drug delivery. Factors and theories that determine the physicochemical and biokinetic behaviors of NPs are discussed, along with the observed toxicological effects of NPs on cells. Key thermodynamic and kinetic models that explain the sources of energy transfer from NPs to biological targets are summarized, in addition to quantitative structural activity relationship (QSAR) modeling efforts. Future challenges for nanotoxicological research are discussed. We conclude that NP studies based on cell culture are often inconsistent and underestimate the toxicity of NPs. Thus, the effect of NPs needs to be examined in whole animal systems.

[1]  Kirsten Sandvig,et al.  Endocytosis and intracellular transport of nanoparticles: Present knowledge and need for future studies , 2011 .

[2]  A. Tropsha,et al.  Quantitative nanostructure-activity relationship modeling. , 2010, ACS nano.

[3]  Lisa Truong,et al.  Media ionic strength impacts embryonic responses to engineered nanoparticle exposure , 2012, Nanotoxicology.

[4]  Yong Xu,et al.  The absolute energy positions of conduction and valence bands of selected semiconducting minerals , 2000 .

[5]  Tanapon Phenrat,et al.  Nanoparticle aggregation: challenges to understanding transport and reactivity in the environment. , 2010, Journal of environmental quality.

[6]  Kenneth A. Dawson,et al.  High Content Analysis Provides Mechanistic Insights on the Pathways of Toxicity Induced by Amine-Modified Polystyrene Nanoparticles , 2014, PloS one.

[7]  Xingyu Jiang,et al.  The molecular mechanism of action of bactericidal gold nanoparticles on Escherichia coli. , 2012, Biomaterials.

[8]  S. Ghosh,et al.  Signaling gene cascade in silver nanoparticle induced apoptosis. , 2010, Colloids and surfaces. B, Biointerfaces.

[9]  Jerzy Leszczynski,et al.  Using nano-QSAR to predict the cytotoxicity of metal oxide nanoparticles. , 2011, Nature nanotechnology.

[10]  Robert L. Tanguay,et al.  Differential stability of lead sulfide nanoparticles influences biological responses in embryonic zebrafish , 2011, Archives of Toxicology.

[11]  N. Kruhlak,et al.  An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: II. Identification of genotoxicants, reprotoxicants, and carcinogens using in silico methods. , 2006, Regulatory toxicology and pharmacology : RTP.

[12]  Stacey L. Harper,et al.  Systematic Evaluation of Nanomaterial Toxicity: Utility of Standardized Materials and Rapid Assays , 2011, ACS nano.

[13]  P. Chakrabarti,et al.  Structure and activity of lysozyme on binding to ZnO nanoparticles. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[14]  Tetsu K. Tokunaga,et al.  Kinetic stability of hematite nanoparticles: the effect of particle sizes , 2008 .

[15]  I. Venditti,et al.  Lipolytic enzymes with improved activity and selectivity upon adsorption on polymeric nanoparticles. , 2007, Biomacromolecules.

[16]  S. K. Sundaram,et al.  Adsorbed proteins influence the biological activity and molecular targeting of nanomaterials. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[17]  Á. Delgado,et al.  Study of the colloidal stability of concentrated bimodal magnetic fluids. , 2007, Journal of colloid and interface science.

[18]  Fengjuan Wang,et al.  The biomolecular corona is retained during nanoparticle uptake and protects the cells from the damage induced by cationic nanoparticles until degraded in the lysosomes. , 2013, Nanomedicine : nanotechnology, biology, and medicine.

[19]  Morteza Mahmoudi,et al.  Protein-Nanoparticle Interactions , 2013 .

[20]  L. Yin,et al.  The immune toxicity of titanium dioxide on primary pulmonary alveolar macrophages relies on their surface area and crystal structure. , 2010, Journal of nanoscience and nanotechnology.

[21]  U. Schubert,et al.  Surface Modification and Functionalization of Metal and Metal Oxide Nanoparticles by Organic Ligands , 2008 .

[22]  R. Müller,et al.  Polysorbate-stabilized solid lipid nanoparticles as colloidal carriers for intravenous targeting of drugs to the brain: Comparison of plasma protein adsorption patterns , 2005, Journal of drug targeting.

[23]  V. Colvin.  The potential environmental impact of engineered nanomaterials , 2003, Nature Biotechnology.

[24]  Yin-Sheng Ma,et al.  Interaction of nano-TiO2 with lysozyme: insights into the enzyme toxicity of nanosized particles , 2010, Environmental science and pollution research international.

[25]  L. Zhang,et al.  Nanoparticles in Medicine: Therapeutic Applications and Developments , 2008, Clinical pharmacology and therapeutics.

[26]  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.

[27]  Andrew P Worth,et al.  A theoretical framework for predicting the oxidative stress potential of oxide nanoparticles , 2011, Nanotoxicology.

[28]  J. West,et al.  The Differential Cytotoxicity of Water-Soluble Fullerenes , 2004 .

[29]  Craig A. Poland,et al.  Zeta potential and solubility to toxic ions as mechanisms of lung inflammation caused by metal/metal oxide nanoparticles. , 2012, Toxicological sciences : an official journal of the Society of Toxicology.

[30]  Jonathan S Dordick,et al.  Silica nanoparticle size influences the structure and enzymatic activity of adsorbed lysozyme. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[31]  Kenneth A Dawson,et al.  Suppression of nanoparticle cytotoxicity approaching in vivo serum concentrations: limitations of in vitro testing for nanosafety. , 2014, Nanoscale.

[32]  Andrew P. Worth,et al.  QSAR modeling of nanomaterials. , 2011, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[33]  Lisa Truong,et al.  Persistent adult zebrafish behavioral deficits results from acute embryonic exposure to gold nanoparticles. , 2012, Comparative biochemistry and physiology. Toxicology & pharmacology : CBP.

[34]  M. Wiesner,et al.  Chemical stability of metallic nanoparticles: a parameter controlling their potential cellular toxicity in vitro. , 2009, Environmental pollution.

[35]  S. Hussain,et al.  Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster. , 2010, Toxicology and applied pharmacology.

[36]  Min Chen,et al.  Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles. , 2005, Experimental cell research.

[37]  Aravind Subramanian,et al.  Perturbational profiling of nanomaterial biologic activity , 2008, Proceedings of the National Academy of Sciences.

[38]  Marco P Monopoli,et al.  Biomolecular coronas provide the biological identity of nanosized materials. , 2012, Nature nanotechnology.

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

[40]  Joel G. Pounds,et al.  Dysregulation of macrophage activation profiles by engineered nanoparticles. , 2013, ACS nano.

[41]  Philip M. Kelly,et al.  Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. , 2013, Nature nanotechnology.

[42]  G. Vecchio,et al.  Mutagenic effects of gold nanoparticles induce aberrant phenotypes in Drosophila melanogaster. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[43]  Robert N Grass,et al.  In vitro cytotoxicity of oxide nanoparticles: comparison to asbestos, silica, and the effect of particle solubility. , 2006, Environmental science & technology.

[44]  David B Warheit,et al.  Assessing toxicity of fine and nanoparticles: comparing in vitro measurements to in vivo pulmonary toxicity profiles. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[45]  N. Kruhlak,et al.  An analysis of genetic toxicity, reproductive and developmental toxicity, and carcinogenicity data: I. Identification of carcinogens using surrogate endpoints. , 2006, Regulatory toxicology and pharmacology : RTP.

[46]  Mehmet Fatih Yanik,et al.  Microfluidic system for on-chip high-throughput whole-animal sorting and screening at subcellular resolution , 2007, Proceedings of the National Academy of Sciences.

[47]  David M. Reif,et al.  Activity profiles of 309 ToxCast™ chemicals evaluated across 292 biochemical targets. , 2011, Toxicology.

[48]  Chi-Ming Che,et al.  Proteomic analysis of the mode of antibacterial action of silver nanoparticles. , 2006, Journal of proteome research.

[49]  Jim E Riviere,et al.  An index for characterization of nanomaterials in biological systems. , 2010, Nature nanotechnology.

[50]  P. Reddanna,et al.  Inflammatory responses of RAW 264.7 macrophages upon exposure to nanoparticles: Role of ROS-NFκB signaling pathway , 2011, Nanotoxicology.

[51]  A. Nel,et al.  Self-organizing map analysis of toxicity-related cell signaling pathways for metal and metal oxide nanoparticles. , 2011, Environmental science & technology.

[52]  Andrew Worth,et al.  Applying quantitative structure-activity relationship approaches to nanotoxicology: current status and future potential. , 2013, Toxicology.

[53]  Ravi S Kane,et al.  Structure, function, and stability of enzymes covalently attached to single-walled carbon nanotubes. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[54]  Marina A Dobrovolskaia,et al.  Nanoparticles and the immune system. , 2010, Endocrinology.

[55]  Peng Wang,et al.  In vitro evaluation of cytotoxicity of engineered metal oxide nanoparticles. , 2009, The Science of the total environment.

[56]  Jinshun Zhao,et al.  Titanium dioxide nanoparticles: a review of current toxicological data , 2013, Particle and Fibre Toxicology.

[57]  Lutz Mädler,et al.  Use of metal oxide nanoparticle band gap to develop a predictive paradigm for oxidative stress and acute pulmonary inflammation. , 2012, ACS nano.

[58]  David M. Reif,et al.  Multidimensional in vivo hazard assessment using zebrafish. , 2014, Toxicological sciences : an official journal of the Society of Toxicology.

[59]  Ajay Kumar Gupta,et al.  Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. , 2005, Biomaterials.

[60]  Tian Xia,et al.  Processing pathway dependence of amorphous silica nanoparticle toxicity: colloidal vs pyrolytic. , 2012, Journal of the American Chemical Society.

[61]  Dong Woo Kim,et al.  Gold nanoparticles attenuate LPS-induced NO production through the inhibition of NF-kappaB and IFN-beta/STAT1 pathways in RAW264.7 cells. , 2010, Nitric oxide : biology and chemistry.

[62]  Frédéric Cardinaux,et al.  Equilibrium cluster formation in concentrated protein solutions and colloids , 2004, Nature.

[63]  A. von Mikecz,et al.  In Caenorhabditis elegans Nanoparticle-Bio-Interactions Become Transparent: Silica-Nanoparticles Induce Reproductive Senescence , 2009, PloS one.

[64]  Alexander Tropsha,et al.  Exploring quantitative nanostructure-activity relationships (QNAR) modeling as a tool for predicting biological effects of manufactured nanoparticles. , 2011, Combinatorial chemistry & high throughput screening.

[65]  S. Radford,et al.  Nucleation of protein fibrillation by nanoparticles , 2007, Proceedings of the National Academy of Sciences.

[66]  G. Oberdörster,et al.  Safety assessment for nanotechnology and nanomedicine: concepts of nanotoxicology , 2010, Journal of internal medicine.

[67]  Parag Aggarwal,et al.  Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. , 2009, Advanced drug delivery reviews.

[68]  Robert L Tanguay,et al.  Integrating zebrafish toxicology and nanoscience for safer product development. , 2013, Green chemistry : an international journal and green chemistry resource : GC.

[69]  F. Kiessling.  Molecular and Cellular MR Imaging , 2007 .

[70]  Benjamin Gilbert,et al.  Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties. , 2008, ACS nano.

[71]  Y. Yoshihisa,et al.  The anti-inflammatory effects of platinum nanoparticles on the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages , 2012, Inflammation Research.

[72]  Jiaqi Lin,et al.  Penetration of lipid membranes by gold nanoparticles: insights into cellular uptake, cytotoxicity, and their relationship. , 2010, ACS nano.

[73]  R. Weissleder,et al.  Cell-specific targeting of nanoparticles by multivalent attachment of small molecules , 2005, Nature Biotechnology.