Adsorption of plasma proteins on uncoated PLGA nanoparticles.

The biodistribution of nanoparticles is significantly influenced by their interaction with plasma proteins. In order to optimize and possibly monitor the delivery of drugs bound to nanoparticles across the blood-brain barrier (BBB), the protein adsorption pattern of uncoated poly(lactic-co-glycolic acid) (PLGA) nanoparticles after their incubation in human plasma was studied by mass spectrometry. After washing of the particles with water, the proteins were directly digested on the nanoparticle surface using trypsin and then analyzed by nLC MALDI-TOF/TOF. Up to now, the standard method for investigation into the plasma protein adsorption to the particles was 2D gel electrophoresis (2D-PAGE), in certain cases followed by mass spectrometry. The non-gel-based method proposed in the present study provides novel insights into the protein corona surrounding the nanoparticles. The proteins adsorbed on the PLGA nanoparticles after incubation that gave the best signal in terms of quality (high MASCOT score) in human plasma were apolipoprotein E, vitronectin, histidine-rich glycoprotein and kininogen-1. These proteins also are constituents of HDL.

[1]  R. Müller,et al.  'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption. , 2000, Colloids and surfaces. B, Biointerfaces.

[2]  T. Veenstra,et al.  The Human Plasma Proteome , 2004, Molecular & Cellular Proteomics.

[3]  J. Kreuter,et al.  Covalent attachment of apolipoprotein A-I and apolipoprotein B-100 to albumin nanoparticles enables drug transport into the brain. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[4]  M. Frank,et al.  The role of complement in inflammation and phagocytosis. , 1991, Immunology today.

[5]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[6]  Pier Giorgio Righetti,et al.  Proteome analysis in the clinical chemistry laboratory: myth or reality? , 2005, Clinica chimica acta; international journal of clinical chemistry.

[7]  H. Maeda The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. , 2001, Advances in enzyme regulation.

[8]  M. Reilly,et al.  HDL proteomics: pot of gold or Pandora's box? , 2007, The Journal of clinical investigation.

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

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

[11]  P. Couvreur,et al.  Analysis of plasma protein adsorption onto PEGylated nanoparticles by complementary methods: 2‐DE, CE and Protein Lab‐on‐chip® system , 2007, Electrophoresis.

[12]  R. Müller,et al.  Influence of polysaccharide coating on the interactions of nanoparticles with biological systems. , 2006, Biomaterials.

[13]  M. Lück,et al.  Plasma protein adsorption on biodegradable microspheres consisting of poly(D,L-lactide-co-glycolide), poly(L-lactide) or ABA triblock copolymers containing poly(oxyethylene). Influence of production method and polymer composition. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[14]  R. Müller,et al.  Interactions of blood proteins with poly(isobutylcyanoacrylate) nanoparticles decorated with a polysaccharidic brush. , 2005, Biomaterials.

[15]  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.

[16]  K. Geiger,et al.  Chemotherapy of glioblastoma in rats using doxorubicin‐loaded nanoparticles , 2004, International journal of cancer.

[17]  M. Lück,et al.  Analysis of plasma protein adsorption on polymeric nanoparticles with different surface characteristics. , 1998, Journal of biomedical materials research.

[18]  M. Hulett,et al.  Histidine-rich glycoprotein: the Swiss Army knife of mammalian plasma. , 2011, Blood.

[19]  R. Müller,et al.  Adsorption kinetics of plasma proteins on solid lipid nanoparticles for drug targeting. , 2005, International journal of pharmaceutics.

[20]  Christine Vauthier,et al.  Methods for the Preparation and Manufacture of Polymeric Nanoparticles , 2009, Pharmaceutical Research.

[21]  R. Müller,et al.  Chemotherapy of brain tumour using doxorubicin bound to surfactant-coated poly(butyl cyanoacrylate) nanoparticles: revisiting the role of surfactants. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[22]  G. Borchard,et al.  The Role of Serum Complement on the Organ Distribution of Intravenously Administered Poly (methyl methacrylate) Nanoparticles: Effects of Pre-Coating with Plasma and with Serum Complement , 1996, Pharmaceutical Research.

[23]  Jong Hoon Park,et al.  Analysis of Human Plasma Proteome by 2DE‐ and 2D nanoLC‐Based Mass Spectrometry , 2006, Preparative biochemistry & biotechnology.

[24]  M. Glatzel,et al.  Efficient Chemotherapy of Rat Glioblastoma Using Doxorubicin-Loaded PLGA Nanoparticles with Different Stabilizers , 2011, PloS one.

[25]  S Moein Moghimi,et al.  Complement: alive and kicking nanomedicines. , 2009, Journal of biomedical nanotechnology.

[26]  J. Kreuter,et al.  Drug delivery to the brain using surfactant-coated poly(lactide-co-glycolide) nanoparticles: influence of the formulation parameters. , 2010, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[27]  D. Simberg,et al.  Interactions of nanoparticles with plasma proteins: implication on clearance and toxicity of drug delivery systems , 2011, Expert opinion on drug delivery.

[28]  Maria Chiara Pietrogrande,et al.  Spot overlapping in two‐dimensional polyacrylamide gel electrophoresis maps: Relevance to proteomics , 2003, Electrophoresis.

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

[30]  H. von Briesen,et al.  Uptake Mechanism of ApoE-Modified Nanoparticles on Brain Capillary Endothelial Cells as a Blood-Brain Barrier Model , 2012, PloS one.

[31]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[32]  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.

[33]  Christoph H Borchers,et al.  Multiple Reaction Monitoring-based, Multiplexed, Absolute Quantitation of 45 Proteins in Human Plasma* , 2009, Molecular & Cellular Proteomics.

[34]  R. Müller,et al.  Correlation of the surface hydrophobicity of 14C-poly(methyl methacrylate) nanoparticles to their body distribution , 1992 .

[35]  R. Müller,et al.  Protein adsorption patterns on poloxamer- and poloxamine-stabilized solid lipid nanoparticles (SLN). , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[36]  Sara Linse,et al.  Detailed identification of plasma proteins adsorbed on copolymer nanoparticles. , 2007, Angewandte Chemie.

[37]  D. Hochstrasser,et al.  Colloidal carriers for intravenous drug targeting: Plasma protein adsorption patterns on surface‐modified latex particles evaluated by two‐dimensional polyacrylamide gel electrophoresis , 1993, Electrophoresis.

[38]  Andrew N Hoofnagle,et al.  Lipoproteomics: using mass spectrometry-based proteomics to explore the assembly, structure, and function of lipoproteins , 2009, Journal of Lipid Research.