Bridge over troubled waters: understanding the synthetic and biological identities of engineered nanomaterials.

Engineered nanomaterials offer exciting opportunities for 'smart' drug delivery and in vivo imaging of disease processes, as well as in regenerative medicine. The ability to manipulate matter at the nanoscale enables many new properties that are both desirable and exploitable, but the same properties could also give rise to unexpected toxicities that may adversely affect human health. Understanding the physicochemical properties that drive toxicological outcomes is a formidable challenge as it is not trivial to separate and, hence, to pinpoint individual material characteristics of nanomaterials. In addition, nanomaterials that interact with biological systems are likely to acquire a surface corona of biomolecules that may dictate their biological behavior. Indeed, we propose that it is the combination of material-intrinsic properties (the 'synthetic identity') and context-dependent properties determined, in part, by the bio-corona of a given biological compartment (the 'biological identity') that will determine the interactions of engineered nanomaterials with cells and tissues and subsequent outcomes. The delineation of these entwined 'identities' of engineered nanomaterials constitutes the bridge between nanotoxicological research and nanomedicine.

[1]  Albert Duschl,et al.  Hardening of the nanoparticle-protein corona in metal (Au, Ag) and oxide (Fe3O4, CoO, and CeO2) nanoparticles. , 2011, Small.

[2]  Rui Hu,et al.  A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots. , 2012, Nature nanotechnology.

[3]  Mark B. Carter,et al.  The Targeted Delivery of Multicomponent Cargos to Cancer Cells via Nanoporous Particle-Supported Lipid Bilayers , 2011, Nature materials.

[4]  R. Zhou,et al.  Binding of blood proteins to carbon nanotubes reduces cytotoxicity , 2011, Proceedings of the National Academy of Sciences.

[5]  Judith Klein-Seetharaman,et al.  Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. , 2010, Nature nanotechnology.

[6]  G. Oberdörster,et al.  Nanotoxicology: An Emerging Discipline Evolving from Studies of Ultrafine Particles , 2005, Environmental health perspectives.

[7]  M. Prato,et al.  Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Teófilo Rojo,et al.  The challenge to relate the physicochemical properties of colloidal nanoparticles to their cytotoxicity. , 2013, Accounts of chemical research.

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

[10]  Bengt Fadeel,et al.  Factoring-in agglomeration of carbon nanotubes and nanofibers for better prediction of their toxicity versus asbestos , 2012, Particle and Fibre Toxicology.

[11]  Francesco Stellacci,et al.  Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. , 2008, Nature materials.

[12]  Forrest M Kievit,et al.  Cancer Nanotheranostics: Improving Imaging and Therapy by Targeted Delivery Across Biological Barriers , 2011, Advanced materials.

[13]  Jim E Riviere,et al.  Pharmacokinetics of nanomaterials: an overview of carbon nanotubes, fullerenes and quantum dots. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[14]  Robert Rallo,et al.  Use of a high-throughput screening approach coupled with in vivo zebrafish embryo screening to develop hazard ranking for engineered nanomaterials. , 2011, ACS nano.

[15]  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.

[16]  Kanlaya Prapainop,et al.  A chemical approach for cell-specific targeting of nanomaterials: small-molecule-initiated misfolding of nanoparticle corona proteins. , 2012, Journal of the American Chemical Society.

[17]  Sara Linse,et al.  Understanding the nanoparticle–protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles , 2007, Proceedings of the National Academy of Sciences.

[18]  David Y Lai,et al.  Toward toxicity testing of nanomaterials in the 21st century: a paradigm for moving forward. , 2012, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[19]  Bengt Fadeel,et al.  Mechanisms of carbon nanotube-induced toxicity: focus on oxidative stress. , 2012, Toxicology and applied pharmacology.

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

[21]  J. Janisse,et al.  Dendrimer-Based Postnatal Therapy for Neuroinflammation and Cerebral Palsy in a Rabbit Model , 2012, Science Translational Medicine.

[22]  Peter Wick,et al.  Nanotoxicology: an interdisciplinary challenge. , 2011, Angewandte Chemie.

[23]  James Chen Yong Kah,et al.  Exploiting the protein corona around gold nanorods for loading and triggered release. , 2012, ACS nano.

[24]  R. Niessner,et al.  Multifunctional nanoparticles for dual imaging. , 2011, Analytical chemistry.

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

[26]  Henrike Caysa,et al.  Tumor accumulation of NIR fluorescent PEG-PLA nanoparticles: impact of particle size and human xenograft tumor model. , 2011, ACS nano.

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

[28]  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.

[29]  Warren C W Chan,et al.  Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment. , 2012, Chemical Society reviews.

[30]  Iseult Lynch,et al.  Designing the nanoparticle-biomolecule interface for "targeting and therapeutic delivery". , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[31]  Yuri Volkov,et al.  High-content screening as a universal tool for fingerprinting of cytotoxicity of nanoparticles. , 2008, ACS nano.

[32]  A. Riedinger,et al.  A general synthetic approach for obtaining cationic and anionic inorganic nanoparticles via encapsulation in amphiphilic copolymers. , 2011, Small.

[33]  T. Xia,et al.  Toxic Potential of Materials at the Nanolevel , 2006, Science.

[34]  Andrzej S Pitek,et al.  Reversible versus irreversible binding of transferrin to polystyrene nanoparticles: soft and hard corona. , 2012, ACS nano.

[35]  Warren C W Chan,et al.  Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. , 2007, Nano letters.

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

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

[38]  Heidi Goenaga-Infante,et al.  Dynamic monitoring of metal oxide nanoparticle toxicity by label free impedance sensing. , 2012, Chemical research in toxicology.

[39]  Simon C Watkins,et al.  Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. , 2012, Blood.

[40]  Bengt Fadeel,et al.  Nanotoxicology: no small matter. , 2010, Nanoscale.

[41]  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.

[42]  Lorenz M Mayr,et al.  Novel trends in high-throughput screening. , 2009, Current opinion in pharmacology.

[43]  Minnamari Vippola,et al.  Proteomic characterization of engineered nanomaterial-protein interactions in relation to surface reactivity. , 2011, ACS nano.

[44]  Bengt Fadeel,et al.  Close encounters of the small kind: adverse effects of man-made materials interfacing with the nano-cosmos of biological systems. , 2010, Annual review of pharmacology and toxicology.

[45]  Brahim Lounis,et al.  Cathepsin L digestion of nanobioconjugates upon endocytosis. , 2009, ACS nano.

[46]  A. Caminade,et al.  A Phosphorus-Based Dendrimer Targets Inflammation and Osteoclastogenesis in Experimental Arthritis , 2011, Science Translational Medicine.

[47]  J. Lötvall,et al.  Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells , 2007, Nature Cell Biology.

[48]  P. Baron,et al.  Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[49]  Jean-Luc Coll,et al.  Physico-chemical parameters that govern nanoparticles fate also dictate rules for their molecular evolution. , 2012, Advanced drug delivery reviews.

[50]  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.

[51]  Li Tang,et al.  Synthesis and biological response of size-specific, monodisperse drug-silica nanoconjugates. , 2012, ACS nano.

[52]  M. Uesaka,et al.  Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. , 2011, Nature nanotechnology.

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

[54]  Dai Fukumura,et al.  Multistage nanoparticle delivery system for deep penetration into tumor tissue , 2011, Proceedings of the National Academy of Sciences.

[55]  Judith Klein-Seetharaman,et al.  Adsorption of surfactant lipids by single-walled carbon nanotubes in mouse lung upon pharyngeal aspiration. , 2012, ACS nano.

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

[57]  Brahim Lounis,et al.  Direct investigation of intracellular presence of gold nanoparticles via photothermal heterodyne imaging. , 2011, ACS nano.

[58]  C. Alexiou,et al.  Locoregional cancer treatment with magnetic drug targeting. , 2000, Cancer research.

[59]  Lucía Gutiérrez,et al.  Biological applications of magnetic nanoparticles. , 2012, Chemical Society reviews.

[60]  Istvan Toth,et al.  Nanoparticle-induced unfolding of fibrinogen promotes Mac-1 receptor activation and inflammation. , 2011, Nature nanotechnology.

[61]  Mauro Ferrari,et al.  Nanomedicine--challenge and perspectives. , 2009, Angewandte Chemie.

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

[63]  M. Pickard,et al.  The transfection of multipotent neural precursor/stem cell transplant populations with magnetic nanoparticles. , 2011, Biomaterials.

[64]  Marco Zanella,et al.  Biological applications of gold nanoparticles. , 2008, Chemical Society reviews.

[65]  R. Stafford,et al.  Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Sanjay Mathur,et al.  Mapping the surface adsorption forces of nanomaterials in biological systems. , 2011, ACS nano.

[67]  James H. Adair,et al.  Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer. , 2008, ACS nano.

[68]  Davoud Ahmadvand,et al.  Material properties in complement activation. , 2011, Advanced drug delivery reviews.

[69]  Ruth Duncan,et al.  Polyvalent dendrimer glucosamine conjugates prevent scar tissue formation , 2004, Nature Biotechnology.

[70]  S. Toyokuni,et al.  Diameter and rigidity of multiwalled carbon nanotubes are critical factors in mesothelial injury and carcinogenesis , 2011, Proceedings of the National Academy of Sciences.

[71]  Manuela Semmler-Behnke,et al.  Size and surface charge of gold nanoparticles determine absorption across intestinal barriers and accumulation in secondary target organs after oral administration , 2011, Nanotoxicology.

[72]  Samuel I Stupp,et al.  Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair , 2011, Proceedings of the National Academy of Sciences.

[73]  R. Jain,et al.  Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner , 2012, Nature nanotechnology.

[74]  R. Duncan,et al.  Nanomedicine(s) under the microscope. , 2011, Molecular pharmaceutics.

[75]  Staffan Strömblad,et al.  RETRACTED: Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study , 2011, The Lancet.

[76]  D. Irvine,et al.  Bio-inspired, bioengineered and biomimetic drug delivery carriers , 2011, Nature Reviews Drug Discovery.

[77]  R Damoiseaux,et al.  No time to lose--high throughput screening to assess nanomaterial safety. , 2011, Nanoscale.

[78]  Ronnie H. Fang,et al.  Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform , 2011, Proceedings of the National Academy of Sciences.

[79]  A. Hursthouse,et al.  Working together: the combined application of a magnetic field and penetratin for the delivery of magnetic nanoparticles to cells in 3D. , 2011, ACS nano.

[80]  Saba Tm,et al.  Kupffer cell phagocytosis and metabolism of a variety of particles as a function of opsonization. , 1965 .

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

[82]  Alison Elder,et al.  Correlating physico-chemical with toxicological properties of nanoparticles: the present and the future. , 2010, ACS nano.

[83]  Maurizio Prato,et al.  Carbon-nanotube shape and individualization critical for renal excretion. , 2008, Small.

[84]  Kenneth A. Dawson,et al.  Effects of the presence or absence of a protein corona on silica nanoparticle uptake and impact on cells. , 2012, ACS nano.

[85]  Wendelin J Stark,et al.  Nanoparticles in biological systems. , 2011, Angewandte Chemie.

[86]  Nastassja A. Lewinski,et al.  Cytotoxicity of nanoparticles. , 2008, Small.

[87]  Florence Gazeau,et al.  Nanomagnetic sensing of blood plasma protein interactions with iron oxide nanoparticles: impact on macrophage uptake. , 2012, ACS nano.

[88]  Hak Soo Choi,et al.  Rapid translocation of nanoparticles from the lung airspaces to the body , 2010, Nature Biotechnology.

[89]  S M Moghimi,et al.  Factors controlling nanoparticle pharmacokinetics: an integrated analysis and perspective. , 2012, Annual review of pharmacology and toxicology.

[90]  Mark E. Davis,et al.  Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles , 2010, Nature.

[91]  Navid B. Saleh,et al.  Does shape matter? Bioeffects of gold nanomaterials in a human skin cell model. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[92]  Mandy B. Esch,et al.  Oral exposure to polystyrene nanoparticles affects iron absorption. , 2012, Nature nanotechnology.

[93]  R. Shah,et al.  Supramolecular design of self-assembling nanofibers for cartilage regeneration , 2010, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Robert Langer,et al.  Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile , 2012, Science Translational Medicine.

[95]  Neetu Singh,et al.  Nanoparticles that communicate in vivo to amplify tumour targeting. , 2011, Nature materials.

[96]  Anders Hult,et al.  Stability and biocompatibility of a library of polyester dendrimers in comparison to polyamidoamine dendrimers. , 2012, Biomaterials.

[97]  M. Mortimer,et al.  High throughput kinetic Vibrio fischeri bioluminescence inhibition assay for study of toxic effects of nanoparticles. , 2008, Toxicology in vitro : an international journal published in association with BIBRA.

[98]  Esther Parker,et al.  ELECTRON MICROSCOPY OF HELA CELLS AFTER THE INGESTION OF COLLOIDAL GOLD , 1957, The Journal of biophysical and biochemical cytology.

[99]  Bengt Fadeel,et al.  Safety assessment of nanomaterials: implications for nanomedicine. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[100]  T. Mihaljevic,et al.  Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping , 2004, Nature Biotechnology.

[101]  Li Wei,et al.  Sharper and faster "nano darts" kill more bacteria: a study of antibacterial activity of individually dispersed pristine single-walled carbon nanotube. , 2009, ACS nano.

[102]  F. Collins,et al.  Transforming Environmental Health Protection , 2008, Science.

[103]  Rebecca Robinson,et al.  Intravenous Hemostat: Nanotechnology to Halt Bleeding , 2009, Science Translational Medicine.

[104]  Yasuo Yoshioka,et al.  Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. , 2011, Nature nanotechnology.

[105]  P. Ray Size and shape dependent second order nonlinear optical properties of nanomaterials and their application in biological and chemical sensing. , 2010, Chemical reviews.

[106]  Ji-Ho Park,et al.  Differential proteomics analysis of the surface heterogeneity of dextran iron oxide nanoparticles and the implications for their in vivo clearance. , 2009, Biomaterials.

[107]  N. D. Groodt,et al.  Alterations in the Ultrastructure of the Blood–Air Barrier in the Mouse Lung after Inhalation of Colloidal Gold Particles , 1958, Nature.

[108]  M. Malmsten,et al.  Nanomedicine: reshaping clinical practice , 2010, Journal of internal medicine.

[109]  Stefan Tenzer,et al.  Nanoparticle size is a critical physicochemical determinant of the human blood plasma corona: a comprehensive quantitative proteomic analysis. , 2011, ACS nano.

[110]  Patrick Couvreur,et al.  Translocation of poly(ethylene glycol-co-hexadecyl)cyanoacrylate nanoparticles into rat brain endothelial cells: role of apolipoproteins in receptor-mediated endocytosis. , 2007, Biomacromolecules.

[111]  P. Hunziker,et al.  Designing switchable nanosystems for medical application. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[112]  Ji-Xin Cheng,et al.  Label-free imaging of semiconducting and metallic carbon nanotubes in cells and mice using transient absorption microscopy. , 2011, Nature nanotechnology.

[113]  Moonjung Choi,et al.  Cellular uptake, cytotoxicity, and innate immune response of silica-titania hollow nanoparticles based on size and surface functionality. , 2010, ACS nano.

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

[115]  James L. McGrath,et al.  The influence of protein adsorption on nanoparticle association with cultured endothelial cells. , 2009, Biomaterials.

[116]  Karthikeyan Subramani,et al.  Magnetic resonance imaging tracking of stem cells in vivo using iron oxide nanoparticles as a tool for the advancement of clinical regenerative medicine. , 2011, Chemical reviews.

[117]  Iseult Lynch,et al.  What the cell "sees" in bionanoscience. , 2010, Journal of the American Chemical Society.

[118]  Zhuang Liu,et al.  Carbon nanotubes as photoacoustic molecular imaging agents in living mice. , 2008, Nature nanotechnology.

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

[120]  Pratim Biswas,et al.  Assessing the relevance of in vitro studies in nanotoxicology by examining correlations between in vitro and in vivo data. , 2012, Toxicology.

[121]  D. Ingber,et al.  Reconstituting Organ-Level Lung Functions on a Chip , 2010, Science.

[122]  Bengt Fadeel,et al.  Impaired Clearance and Enhanced Pulmonary Inflammatory/Fibrotic Response to Carbon Nanotubes in Myeloperoxidase-Deficient Mice , 2012, PloS one.

[123]  Thomas Hartung,et al.  Alternative in vitro assays in nanomaterial toxicology. , 2011, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[124]  Wolfgang J Parak,et al.  NIR-light triggered delivery of macromolecules into the cytosol. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[125]  Peter Wick,et al.  The adsorption of biomolecules to multi-walled carbon nanotubes is influenced by both pulmonary surfactant lipids and surface chemistry , 2010, Journal of nanobiotechnology.

[126]  Rodney F. Minchin,et al.  Plasma protein binding of positively and negatively charged polymer-coated gold nanoparticles elicits different biological responses , 2012, Nanotoxicology.

[127]  Claus-Michael Lehr,et al.  The Interplay of Lung Surfactant Proteins and Lipids Assimilates the Macrophage Clearance of Nanoparticles , 2012, PloS one.

[128]  Bengt Fadeel,et al.  Better safe than sorry: Understanding the toxicological properties of inorganic nanoparticles manufactured for biomedical applications. , 2010, Advanced drug delivery reviews.

[129]  S Moein Moghimi,et al.  Distinct polymer architecture mediates switching of complement activation pathways at the nanosphere-serum interface: implications for stealth nanoparticle engineering. , 2010, ACS nano.

[130]  Stephen F Badylak,et al.  RETRACTED: Engineered whole organs and complex tissues , 2012, The Lancet.

[131]  Iseult Lynch,et al.  The evolution of the protein corona around nanoparticles: a test study. , 2011, ACS nano.