Nanoparticle Surface Functionality Dictates Cellular and Systemic Toxicity

Engineered nanoparticles (NPs) have opened new frontiers in therapeutics and diagnostics in recent years. The surface functionality of these nanoparticles often predominates their interactions with various biological components of human body, and proper selection or control of surface functionality can greatly enhance subsequent therapeutic effects of NPs while diminishing their adverse side effects. In this review, we will focus on the effect of surface functionality on the cellular uptake and the transport of NPs by various subcellular processes.

[1]  Kenneth A Dawson.  Leave the policing to others. , 2013, Nature nanotechnology.

[2]  Bengt Fadeel,et al.  Cytotoxic and Proinflammatory Effects of Metal-Based Nanoparticles on THP-1 Monocytes Characterized by Combined Proteomics Approaches. , 2017, Journal of proteome research.

[3]  Kreuter,et al.  Preparation, characterization and cytotoxicity of methylmethacrylate copolymer nanoparticles with a permanent positive surface charge. , 1997, International journal of pharmaceutics.

[4]  Vincent M Rotello,et al.  Inhibition of chymotrypsin through surface binding using nanoparticle-based receptors , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[5]  S. Mitragotri,et al.  Elasticity of nanoparticles influences their blood circulation, phagocytosis, endocytosis, and targeting. , 2015, ACS nano.

[6]  Juan L. Vivero-Escoto,et al.  Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. , 2008, Advanced drug delivery reviews.

[7]  N. Malmstadt,et al.  Deformation and poration of lipid bilayer membranes by cationic nanoparticles , 2013 .

[8]  Vincent M Rotello,et al.  Tunable inhibition and denaturation of alpha-chymotrypsin with amino acid-functionalized gold nanoparticles. , 2005, Journal of the American Chemical Society.

[9]  Huajian Gao,et al.  Kinetics of receptor-mediated endocytosis of elastic nanoparticles. , 2017, Nanoscale.

[10]  Bo Yan,et al.  Surface Charge Controls the Suborgan Biodistributions of Gold Nanoparticles. , 2016, ACS nano.

[11]  T. Ishida,et al.  Anti-PEG IgM elicited by injection of liposomes is involved in the enhanced blood clearance of a subsequent dose of PEGylated liposomes. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[12]  Basit Yameen,et al.  Antiplatelet effect of differentially charged PEGylated lipid-polymer nanoparticles. , 2017, Nanomedicine : nanotechnology, biology, and medicine.

[13]  Dan Peer,et al.  Nanoparticle hydrophobicity dictates immune response. , 2012, Journal of the American Chemical Society.

[14]  A. Karakoti,et al.  Surface functionalization of quantum dots for biological applications. , 2015, Advances in colloid and interface science.

[15]  D. Wright,et al.  Where's the silver? Imaging trace silver coverage on the surface of gold nanorods. , 2014, Journal of the American Chemical Society.

[16]  C. Murphy,et al.  Tuning cellular response to nanoparticles via surface chemistry and aggregation. , 2014, Small.

[17]  S. Doak,et al.  NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. , 2009, Biomaterials.

[18]  V. Rotello,et al.  Reversible "irreversible" inhibition of chymotrypsin using nanoparticle receptors. , 2003, Journal of the American Chemical Society.

[19]  M. Wong Chi Man,et al.  Mesoporous-Silica-Functionalized Nanoparticles for Drug Delivery. , 2015, Chemistry.

[20]  K. Bishop,et al.  Integration of gold nanoparticles into bilayer structures via adaptive surface chemistry. , 2013, Journal of the American Chemical Society.

[21]  K. Higaki,et al.  Time-dependent changes in opsonin amount associated on nanoparticles alter their hepatic uptake characteristics. , 2007, International journal of pharmaceutics.

[22]  Kimberly Hamad-Schifferli,et al.  Gold nanoparticle-cytochrome C complexes: the effect of nanoparticle ligand charge on protein structure. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[23]  V. Rotello,et al.  Modulating Pharmacokinetics, Tumor Uptake and Biodistribution by Engineered Nanoparticles , 2011, PloS one.

[24]  Wei Liu,et al.  Effective cancer targeting and imaging using macrophage membrane-camouflaged upconversion nanoparticles. , 2017, Journal of biomedical materials research. Part A.

[25]  D. R. Baer,et al.  Application of surface chemical analysis tools for characterization of nanoparticles , 2010, Analytical and bioanalytical chemistry.

[26]  Yuliang Zhao,et al.  Exosomes as extrapulmonary signaling conveyors for nanoparticle-induced systemic immune activation. , 2012, Small.

[27]  De-Hao Tsai,et al.  Adsorption and conformation of serum albumin protein on gold nanoparticles investigated using dimensional measurements and in situ spectroscopic methods. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[28]  P. Roach,et al.  'Stealth' nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[29]  Liping Tang,et al.  Nanomaterial cytotoxicity is composition, size, and cell type dependent , 2010, Particle and Fibre Toxicology.

[30]  A. Alexander-Katz,et al.  Cell membranes open "doors" for cationic nanoparticles/biomolecules: insights into uptake kinetics. , 2013, ACS nano.

[31]  Deng-Fwu Hwang,et al.  In vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. , 2007, Environmental science & technology.

[32]  Yong Zhang,et al.  Photocontrolled nanoparticle delivery systems for biomedical applications. , 2014, Accounts of chemical research.

[33]  N. Halas.  Nanoscience under glass: the versatile chemistry of silica nanostructures. , 2008, ACS nano.

[34]  Benoit Dubertret,et al.  Design of new quantum dot materials for deep tissue infrared imaging. , 2013, Advanced drug delivery reviews.

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

[36]  Hong-Yang Chuang,et al.  Directly thiolated modification onto the surface of detonation nanodiamonds. , 2014, ACS applied materials & interfaces.

[37]  Morteza Mahmoudi,et al.  Cell "vision": complementary factor of protein corona in nanotoxicology. , 2012, Nanoscale.

[38]  Taro Shimizu,et al.  PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[39]  Erik K Richman,et al.  The nanomaterial characterization bottleneck. , 2009, ACS nano.

[40]  Sara Linse,et al.  Polystyrene nanoparticles affecting blood coagulation. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[41]  Elodie Boisselier,et al.  Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. , 2009, Chemical Society reviews.

[42]  Vincent M Rotello,et al.  The role of surface functionality on acute cytotoxicity, ROS generation and DNA damage by cationic gold nanoparticles. , 2010, Small.

[43]  Parag Aggarwal,et al.  Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. , 2008, Molecular pharmaceutics.

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

[45]  Jackie Y. Ying,et al.  Synthesis of water-soluble and functionalized nanoparticles by silica coating , 2007 .

[46]  Naomi J Halas,et al.  Gold nanoparticles can induce the formation of protein-based aggregates at physiological pH. , 2009, Nano letters.

[47]  Jeremiah A. Johnson,et al.  PEGylated N-Heterocyclic Carbene Anchors Designed To Stabilize Gold Nanoparticles in Biologically Relevant Media. , 2015, Journal of the American Chemical Society.

[48]  V. Rotello,et al.  Quantitative tracking of protein trafficking to the nucleus using cytosolic protein delivery by nanoparticle-stabilized nanocapsules. , 2015, Bioconjugate chemistry.

[49]  K. Beningo,et al.  Flexible polyacrylamide substrata for the analysis of mechanical interactions at cell-substratum adhesions. , 2002, Methods in cell biology.

[50]  Eric Pridgen,et al.  Factors Affecting the Clearance and Biodistribution of Polymeric Nanoparticles , 2008, Molecular pharmaceutics.

[51]  M. Dobrovolskaia,et al.  Interaction Between Nanoparticles and Plasma Proteins: Effects on Nanoparticle Biodistribution and Toxicity , 2016 .

[52]  N. Jana,et al.  Design and Synthesis of Triphenylphosphonium Functionalized Nanoparticle Probe for Mitochondria Targeting and Imaging , 2015 .

[53]  R. Tenne,et al.  Polymer-assisted fabrication of nanoparticles and nanocomposites , 2008 .

[54]  Tza-Huei Wang,et al.  Erythrocyte Membrane-Coated Upconversion Nanoparticles with Minimal Protein Adsorption for Enhanced Tumor Imaging. , 2017, ACS applied materials & interfaces.

[55]  Mauro Ferrari,et al.  Principles of nanoparticle design for overcoming biological barriers to drug delivery , 2015, Nature Biotechnology.

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

[57]  A. Zahr,et al.  Macrophage uptake of core-shell nanoparticles surface modified with poly(ethylene glycol). , 2006, Langmuir : the ACS journal of surfaces and colloids.

[58]  L. Min,et al.  Detoxifying function of cytochrome c against oxygen toxicity. , 2007, Mitochondrion.

[59]  Igor L. Medintz,et al.  Quantum dot bioconjugates for imaging, labelling and sensing , 2005, Nature materials.

[60]  G. Ulrich Nienhaus,et al.  Impact of protein modification on the protein corona on nanoparticles and nanoparticle-cell interactions. , 2014, ACS nano.

[61]  Kristen N. Duthie,et al.  Wide varieties of cationic nanoparticles induce defects in supported lipid bilayers. , 2008, Nano letters.

[62]  Yaroslava G. Yingling,et al.  Binding of single stranded nucleic acids to cationic ligand functionalized gold nanoparticles. , 2016, Biointerphases.

[63]  Bing Chen,et al.  Transdermal Vascular Endothelial Growth Factor Delivery with Surface Engineered Gold Nanoparticles. , 2017, ACS applied materials & interfaces.

[64]  Kinam Park,et al.  Targeted drug delivery to tumors: myths, reality and possibility. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

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

[66]  M. Ornatska,et al.  Interaction of nanoparticles with lipid membrane. , 2008, Nano letters.

[67]  C. Murphy,et al.  Polyelectrolyte-Coated Gold Nanorods: Synthesis, Characterization and Immobilization , 2005 .

[68]  Katrin Schwarz,et al.  Nanoparticles target distinct dendritic cell populations according to their size , 2008, European journal of immunology.

[69]  J. A. Nason,et al.  Effects of natural organic matter type and concentration on the aggregation of citrate-stabilized gold nanoparticles. , 2012, Journal of environmental monitoring : JEM.

[70]  M. Schulz,et al.  Controlling the localization of polymer-functionalized nanoparticles in mixed lipid/polymer membranes. , 2012, ACS nano.

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

[72]  Q. Pankhurst,et al.  Applications of magnetic nanoparticles in biomedicine , 2003 .

[73]  Yingxi Zhu,et al.  Disruption of supported lipid bilayers by semihydrophobic nanoparticles. , 2011, Journal of the American Chemical Society.

[74]  R. Hamers,et al.  Quantitative determination of ligand densities on nanomaterials by X-ray photoelectron spectroscopy. , 2015, ACS applied materials & interfaces.

[75]  S. Schlecht,et al.  Nanoparticle-induced folding and fibril formation of coiled-coil-based model peptides. , 2010, Small.

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

[77]  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.

[78]  Yu-qiang Ma,et al.  Role of physicochemical properties of coating ligands in receptor-mediated endocytosis of nanoparticles. , 2012, Biomaterials.

[79]  M. Breunig,et al.  Influence of PEGylation on nanoparticle mobility in different models of the extracellular matrix. , 2016, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[80]  Raimo Hartmann,et al.  Surface Functionalization of Nanoparticles with Polyethylene Glycol: Effects on Protein Adsorption and Cellular Uptake. , 2015, ACS nano.

[81]  Alaaldin M. Alkilany,et al.  The gold standard: gold nanoparticle libraries to understand the nano-bio interface. , 2013, Accounts of chemical research.

[82]  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.

[83]  Iseult Lynch,et al.  Are there generic mechanisms governing interactions between nanoparticles and cells? Epitope mapping the outer layer of the protein-material interface , 2007 .

[84]  Y. Barenholz.  Doxil®--the first FDA-approved nano-drug: lessons learned. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[85]  E. Reimhult,et al.  Interaction of Size-Tailored PEGylated Iron Oxide Nanoparticles with Lipid Membranes and Cells. , 2017, ACS biomaterials science & engineering.

[86]  N. Hampp,et al.  Basic Physicochemical Properties of Polyethylene Glycol Coated Gold Nanoparticles that Determine Their Interaction with Cells. , 2016, Angewandte Chemie.

[87]  J. M. Harris,et al.  Effect of pegylation on pharmaceuticals , 2003, Nature Reviews Drug Discovery.

[88]  G. Bernardini,et al.  Zerovalent Fe, Co and Ni nanoparticle toxicity evaluated on SKOV‐3 and U87 cell lines , 2015, Journal of applied toxicology : JAT.

[89]  V. Rotello,et al.  Contrasting effects of exterior and interior hydrophobic moieties in the complexation of amino acid functionalized gold clusters with alpha-chymotrypsin. , 2005, Organic Letters.

[90]  Vincent M Rotello,et al.  Acylsulfonamide-Functionalized Zwitterionic Gold Nanoparticles for Enhanced Cellular Uptake at Tumor pH. , 2015, Angewandte Chemie.

[91]  K. Landfester,et al.  Coating nanoparticles with tunable surfactants facilitates control over the protein corona. , 2017, Biomaterials.

[92]  J. Shumaker-Parry,et al.  Structural study of citrate layers on gold nanoparticles: role of intermolecular interactions in stabilizing nanoparticles. , 2014, Journal of the American Chemical Society.

[93]  V. Rotello,et al.  Biomimetic interactions of proteins with functionalized nanoparticles: a thermodynamic study. , 2007, Journal of the American Chemical Society.

[94]  Anne L. van de Ven,et al.  Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. , 2013, Nature nanotechnology.

[95]  Ning Gu,et al.  Computational investigation of interaction between nanoparticles and membranes: hydrophobic/hydrophilic effect. , 2008, The journal of physical chemistry. B.

[96]  K. Donaldson,et al.  Serum exposed to nanoparticle carbon black displays increased potential to induce macrophage migration. , 2005, Toxicology letters.

[97]  Pauline M Rudd,et al.  The "sweet" side of the protein corona: effects of glycosylation on nanoparticle-cell interactions. , 2015, ACS nano.

[98]  A. Balazs,et al.  Harnessing janus nanoparticles to create controllable pores in membranes. , 2008, ACS nano.

[99]  Morteza Mahmoudi,et al.  Irreversible changes in protein conformation due to interaction with superparamagnetic iron oxide nanoparticles. , 2011, Nanoscale.

[100]  A. Wei,et al.  Citrate-Stabilized Gold Nanorods , 2014, Langmuir : the ACS journal of surfaces and colloids.

[101]  S. Gour,et al.  Deaggregation of nanodiamond powders using salt- and sugar-assisted milling. , 2010, ACS applied materials & interfaces.

[102]  Zhiqiang Gao,et al.  Plasmonic nanoparticles in biomedicine , 2016 .

[103]  Francesco Stellacci,et al.  Effect of surface properties on nanoparticle-cell interactions. , 2010, Small.

[104]  Andrew Emili,et al.  Protein corona fingerprinting predicts the cellular interaction of gold and silver nanoparticles. , 2014, ACS nano.

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

[106]  E. Traversa,et al.  Pharmacological potential of cerium oxide nanoparticles. , 2011, Nanoscale.

[107]  Walter Kolch,et al.  Big signals from small particles: regulation of cell signaling pathways by nanoparticles. , 2013, Chemical reviews.

[108]  V. Rotello,et al.  The role of ligand coordination on the cytotoxicity of cationic quantum dots in HeLa cells. , 2013, Nanoscale.

[109]  Sandra L. Schmid,et al.  Regulated portals of entry into the cell , 2003, Nature.

[110]  Younan Xia,et al.  Gold nanostructures: engineering their plasmonic properties for biomedical applications. , 2006, Chemical Society reviews.

[111]  T. Aida,et al.  Chaperonin-mediated stabilization and ATP-triggered release of semiconductor nanoparticles. , 2003 .

[112]  D. Cao,et al.  Nanoparticle hardness controls the internalization pathway for drug delivery. , 2015, Nanoscale.

[113]  Samir Mitragotri,et al.  Impact of particle elasticity on particle‐based drug delivery systems☆ , 2017, Advanced drug delivery reviews.

[114]  Chad A Mirkin,et al.  Gold nanoparticles for biology and medicine. , 2010, Angewandte Chemie.

[115]  Xiaolu Yang,et al.  TIPE2, a Negative Regulator of Innate and Adaptive Immunity that Maintains Immune Homeostasis , 2008, Cell.

[116]  T. Xia,et al.  Understanding biophysicochemical interactions at the nano-bio interface. , 2009, Nature materials.

[117]  Xiguang Chen,et al.  Mechanism of surface charge triggered intestinal epithelial tight junction opening upon chitosan nanoparticles for insulin oral delivery. , 2017, Carbohydrate polymers.

[118]  Mostafa A. El-Sayed,et al.  The golden age: gold nanoparticles for biomedicine. , 2012, Chemical Society reviews.

[119]  C. Murphy,et al.  Best Practices for the Reporting of Colloidal Inorganic Nanomaterials , 2015 .

[120]  J. Bacri,et al.  Intracellular uptake of anionic superparamagnetic nanoparticles as a function of their surface coating. , 2003, Biomaterials.

[121]  N. Simionescu,et al.  Anionized and cationized hemeundecapeptides as probes for cell surface charge and permeability studies: differentiated labeling of endothelial plasmalemmal vesicles , 1985, The Journal of cell biology.

[122]  Vincent M. Rotello,et al.  Tuning Payload Delivery in Tumour Cylindroids using Gold Nanoparticles , 2010, Nature nanotechnology.

[123]  Morteza Mahmoudi,et al.  Toxicity evaluations of superparamagnetic iron oxide nanoparticles: cell "vision" versus physicochemical properties of nanoparticles. , 2011, ACS nano.

[124]  Pengcheng Zhang,et al.  Cancer Cell Membrane‐Coated Gold Nanocages with Hyperthermia‐Triggered Drug Release and Homotypic Target Inhibit Growth and Metastasis of Breast Cancer , 2020, Advanced Functional Materials.

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

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

[127]  Dennis E Discher,et al.  Minimal " Self " Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles References and Notes , 2022 .

[128]  Peter Ramge,et al.  Apolipoprotein-mediated Transport of Nanoparticle-bound Drugs Across the Blood-Brain Barrier , 2002, Journal of drug targeting.

[129]  A. Basu,et al.  Core functionalization of hollow polymer nanocapsules. , 2009, Journal of the American Chemical Society.

[130]  Hong-Zhuan Chen,et al.  In vivo tumor targeting of tumor necrosis factor-alpha-loaded stealth nanoparticles: effect of MePEG molecular weight and particle size. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[131]  Kenneth A. Dawson,et al.  Nanotoxicology: nanoparticles reconstruct lipids. , 2009, Nature nanotechnology.

[132]  V. Rotello,et al.  The role of surface functionality in determining nanoparticle cytotoxicity. , 2013, Accounts of chemical research.

[133]  G. Drewes,et al.  Tracking cancer drugs in living cells by thermal profiling of the proteome , 2014, Science.

[134]  K. Dawson,et al.  In situ characterization of nanoparticle biomolecular interactions in complex biological media by flow cytometry , 2016, Nature Communications.

[135]  Richard A Flavell,et al.  Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy. , 2009, Vaccine.

[136]  Chung-Yuan Mou,et al.  The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3T3-L1 cells and human mesenchymal stem cells. , 2007, Biomaterials.

[137]  J. Ferri,et al.  Aggregation kinetics and colloidal stability of functionalized nanoparticles. , 2015, Advances in colloid and interface science.

[138]  Vincent M Rotello,et al.  Effect of nanoparticle surface charge at the plasma membrane and beyond. , 2010, Nano letters.

[139]  Luis M. Liz-Marzán,et al.  Current Challenges toward In Vitro Cellular Validation of Inorganic Nanoparticles , 2016, Bioconjugate chemistry.

[140]  James E Hutchison,et al.  Toward greener nanosynthesis. , 2007, Chemical reviews.

[141]  H. Santos,et al.  Functionalization of alkyne-terminated thermally hydrocarbonized porous silicon nanoparticles with targeting peptides and antifouling polymers: effect on the human plasma protein adsorption. , 2015, ACS applied materials & interfaces.

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

[143]  Anand Gole,et al.  Azide-derivatized gold nanorods: functional materials for "click" chemistry. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[144]  V. Bulmus,et al.  Effect of PEG Grafting Density and Hydrodynamic Volume on Gold Nanoparticle-Cell Interactions: An Investigation on Cell Cycle, Apoptosis, and DNA Damage. , 2016, Langmuir : the ACS journal of surfaces and colloids.

[145]  C. Bräuchle,et al.  Uptake kinetics and nanotoxicity of silica nanoparticles are cell type dependent. , 2013, Small.

[146]  P. Stroeve,et al.  Toxicity of nanomaterials. , 2012, Chemical Society reviews.

[147]  D. Astruc,et al.  Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties, and applications toward biology, catalysis, and nanotechnology. , 2004, Chemical reviews.

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

[149]  Kyoungju Choi,et al.  Protein corona modulation of hepatocyte uptake and molecular mechanisms of gold nanoparticle toxicity , 2017, Nanotoxicology.

[150]  Natalia Barkalina,et al.  Functionalization of mesoporous silica nanoparticles with a cell-penetrating peptide to target mammalian sperm in vitro. , 2015, Nanomedicine.

[151]  V. Rotello,et al.  Tuning the interactions of PEG-coated gold nanorods with BSA and model proteins through insertion of amino or carboxylate groups. , 2015, Journal of inorganic biochemistry.

[152]  Dan Peer,et al.  The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation. , 2010, Biomaterials.

[153]  David B Warheit,et al.  How meaningful are the results of nanotoxicity studies in the absence of adequate material characterization? , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[154]  C. Murphy,et al.  Evidence for patchy lipid layers on gold nanoparticle surfaces. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[155]  H. Dai,et al.  Carbon Nanomaterials for Biological Imaging and Nanomedicinal Therapy. , 2015, Chemical reviews.

[156]  L. Liz‐Marzán,et al.  Anisotropic Noble Metal Nanocrystal Growth: The Role of Halides* , 2014, Colloidal Synthesis of Plasmonic Nanometals.

[157]  Jordi Arbiol,et al.  Hydrophobic gold nanoparticle self-assembly with phosphatidylcholine lipid: membrane-loaded and janus vesicles. , 2010, Nano letters.

[158]  Younan Xia,et al.  Understanding the role of surface charges in cellular adsorption versus internalization by selectively removing gold nanoparticles on the cell surface with a I2/KI etchant. , 2009, Nano letters.

[159]  C. Russell Middaugh,et al.  Nanotechnology in vaccine delivery☆ , 2008, Advanced Drug Delivery Reviews.

[160]  Sung Tae Kim,et al.  Regulation of Macrophage Recognition through the Interplay of Nanoparticle Surface Functionality and Protein Corona. , 2016, ACS nano.

[161]  P. Grutter,et al.  Effect of mechanical properties of hydrogel nanoparticles on macrophage cell uptake , 2009 .

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

[163]  Vincent M Rotello,et al.  Surface properties dictate uptake, distribution, excretion, and toxicity of nanoparticles in fish. , 2010, Small.

[164]  Darrell J Irvine,et al.  Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-responsive core-shell nanoparticles. , 2007, Nano letters.

[165]  Wolfgang J Parak,et al.  The impact of species and cell type on the nanosafety profile of iron oxide nanoparticles in neural cells , 2016, Journal of Nanobiotechnology.

[166]  J. Nguyen,et al.  Local Effects on Airway Inflammation and Systemic Uptake of 5 nm PEGylated and Citrated Gold Nanoparticles in Asthmatic Mice. , 2017, Small.

[167]  R Weltzin,et al.  Role of the glycocalyx in regulating access of microparticles to apical plasma membranes of intestinal epithelial cells: implications for microbial attachment and oral vaccine targeting , 1996, The Journal of experimental medicine.

[168]  Hedi Mattoussi,et al.  Strategies for interfacing inorganic nanocrystals with biological systems based on polymer-coating. , 2015, Chemical Society reviews.

[169]  Robert Langer,et al.  Immunocompatibility properties of lipid-polymer hybrid nanoparticles with heterogeneous surface functional groups. , 2009, Biomaterials.

[170]  V. Rotello,et al.  Probing the protein–nanoparticle interface: the role of aromatic substitution pattern on affinity , 2015, Supramolecular chemistry.

[171]  Lei Zhang,et al.  Softer zwitterionic nanogels for longer circulation and lower splenic accumulation. , 2012, ACS nano.

[172]  Huajian Gao,et al.  Cellular uptake of elastic nanoparticles. , 2011, Physical review letters.

[173]  S. Fiering.  Cancer immunotherapy: Making allies of phagocytes. , 2017, Nature nanotechnology.

[174]  Morteza Mahmoudi,et al.  Personalized protein coronas: a "key" factor at the nanobiointerface. , 2014, Biomaterials science.

[175]  Masaki Ozawa,et al.  A general procedure to functionalize agglomerating nanoparticles demonstrated on nanodiamond. , 2009, ACS nano.

[176]  Xingyu Jiang,et al.  Microfluidic Synthesis of Hybrid Nanoparticles with Controlled Lipid Layers: Understanding Flexibility-Regulated Cell-Nanoparticle Interaction. , 2015, ACS nano.

[177]  Alexandra Flemming.  Autoimmunity: Nanoparticles engineered for antigen-specific immunotherapy , 2016, Nature Reviews Immunology.

[178]  Saber M Hussain,et al.  Assessment of the toxicity of silver nanoparticles in vitro: a mitochondrial perspective. , 2011, Toxicology in vitro : an international journal published in association with BIBRA.

[179]  Laura M Ensign,et al.  PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. , 2016, Advanced drug delivery reviews.

[180]  Sabino Veintemillas-Verdaguer,et al.  The influence of surface functionalization on the enhanced internalization of magnetic nanoparticles in cancer cells , 2009, Nanotechnology.

[181]  Tejal A Desai,et al.  Micromachined devices: the impact of controlled geometry from cell-targeting to bioavailability. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[182]  Rigoberto Hernandez,et al.  Biological Responses to Engineered Nanomaterials: Needs for the Next Decade , 2015, ACS central science.

[183]  Warren C W Chan,et al.  The effect of nanoparticle size, shape, and surface chemistry on biological systems. , 2012, Annual review of biomedical engineering.

[184]  Baoquan Ding,et al.  Tunable Rigidity of (Polymeric Core)–(Lipid Shell) Nanoparticles for Regulated Cellular Uptake , 2015, Advanced materials.

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

[186]  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.

[187]  Vincent M Rotello,et al.  Array-based sensing using nanoparticles: an alternative approach for cancer diagnostics. , 2014, Nanomedicine.

[188]  Pablo Del Pino,et al.  Interfacing engineered nanoparticles with biological systems: anticipating adverse nano-bio interactions. , 2013, Small.

[189]  Sarit S. Agasti,et al.  Gold nanoparticles in chemical and biological sensing. , 2012, Chemical reviews.

[190]  Kenneth A. Dawson,et al.  The need for in situ characterisation in nanosafety assessment: funded transnational access via the QNano research infrastructure , 2012, Nanotoxicology.