Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology.

In biological fluids, proteins bind to the surface of nanoparticles to form a coating known as the protein corona, which can critically affect the interaction of the nanoparticles with living systems. As physiological systems are highly dynamic, it is important to obtain a time-resolved knowledge of protein-corona formation, development and biological relevancy. Here we show that label-free snapshot proteomics can be used to obtain quantitative time-resolved profiles of human plasma coronas formed on silica and polystyrene nanoparticles of various size and surface functionalization. Complex time- and nanoparticle-specific coronas, which comprise almost 300 different proteins, were found to form rapidly (<0.5 minutes) and, over time, to change significantly in terms of the amount of bound protein, but not in composition. Rapid corona formation is found to affect haemolysis, thrombocyte activation, nanoparticle uptake and endothelial cell death at an early exposure time.

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

[2]  Iseult Lynch,et al.  Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles. , 2011, Journal of the American Chemical Society.

[3]  Mahesh Kumar Teli,et al.  Nanotechnology and nanomedicine: going small means aiming big. , 2010, Current pharmaceutical design.

[4]  Robert B Sim,et al.  Surface properties: Immune attack on nanoparticles. , 2011, Nature nanotechnology.

[5]  V. Rasche,et al.  Lysosomal degradation of the carboxydextran shell of coated superparamagnetic iron oxide nanoparticles and the fate of professional phagocytes. , 2010, Biomaterials.

[6]  Ronald J. Moore,et al.  Quantitative proteomics analysis of adsorbed plasma proteins classifies nanoparticles with different surface properties and size , 2011, Proteomics.

[7]  Luigi Calzolai,et al.  Protein--nanoparticle interaction: identification of the ubiquitin--gold nanoparticle interaction site. , 2010, Nano letters.

[8]  Mauro Ferrari,et al.  Nanomedicine—Challenge and Perspectives , 2009 .

[9]  E. Vogler,et al.  Protein adsorption in three dimensions. , 2012, Biomaterials.

[10]  S. Tenzer,et al.  Proteome-wide characterization of the RNA-binding protein RALY-interactome using the in vivo-biotinylation-pulldown-quant (iBioPQ) approach. , 2013, Journal of proteome research.

[11]  S. Loibl,et al.  NO signaling confers cytoprotectivity through the survivin network in ovarian carcinomas. , 2008, Cancer research.

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

[13]  L. Vroman,et al.  Effect of Adsorbed Proteins on the Wettability of Hydrophilic and Hydrophobic Solids , 1962, Nature.

[14]  Kevin Braeckmans,et al.  Polymer-coated nanoparticles interacting with proteins and cells: focusing on the sign of the net charge. , 2013, ACS nano.

[15]  B. Wollenberg,et al.  Functional Characterization of Novel Mutations Affecting Survivin (BIRC5)‐Mediated Therapy Resistance in Head and Neck Cancer Patients , 2013, Human mutation.

[16]  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.

[17]  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.

[18]  D. Begley,et al.  Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain , 2010, Journal of drug targeting.

[19]  Suchi Smita,et al.  Nanoparticles in the environment: assessment using the causal diagram approach , 2012, Environmental Health.

[20]  Marina A Dobrovolskaia,et al.  Evaluation of nanoparticle immunotoxicity. , 2009, Nature nanotechnology.

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

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

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

[24]  Katharina Landfester,et al.  Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line. , 2011, ACS nano.

[25]  U. Schubert,et al.  Poly(2-ethyl-2-oxazoline) as alternative for the stealth polymer poly(ethylene glycol): comparison of in vitro cytotoxicity and hemocompatibility. , 2012, Macromolecular bioscience.

[26]  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.

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

[28]  F. Bäckhed,et al.  Tissue factor and PAR1 promote microbiota-induced intestinal vascular remodelling , 2012, Nature.

[29]  I. Schousboe,et al.  High molecular weight kininogen binds to laminin – characterization and kinetic analysis , 2009, The FEBS journal.

[30]  W. Peukert,et al.  Impact of the nanoparticle-protein corona on colloidal stability and protein structure. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[31]  W. Meier,et al.  Probing bioinspired transport of nanoparticles into polymersomes. , 2012, Angewandte Chemie.

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

[33]  R. Minchin,et al.  Nanomedicine: sizing up targets with nanoparticles. , 2008, Nature nanotechnology.

[34]  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.

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

[36]  M. R. Anoop,et al.  The present and future , 2001 .

[37]  C. Ottmann,et al.  Allosteric inhibition of Taspase1′s pathobiological activity by enforced dimerization in vivo , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[38]  D. Begley,et al.  Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones. , 2009, Journal of controlled release : official journal of the Controlled Release Society.

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

[40]  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.

[41]  Kenneth A. Dawson,et al.  Nanobiotechnology: nanoparticle coronas take shape. , 2011, Nature nanotechnology.

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

[43]  Sara Linse,et al.  Modeling the Time Evolution of the Nanoparticle-Protein Corona in a Body Fluid , 2010, PloS one.

[44]  Colin R. Janssen,et al.  Ecotoxicity and uptake of polymer coated gold nanoparticles , 2013, Nanotoxicology.

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

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

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

[48]  Lutz Mädler,et al.  Nanomaterials in the environment: from materials to high-throughput screening to organisms. , 2011, ACS nano.