title: Component-Specific Analysis of Plasma Protein Corona Formation on Gold Nanoparticles Using Multiplexed Surface Plasmon Resonance.
abstract: At the nano-bio interface, human plasma differentially interacts with engineered nanomaterials through the creation of protein coronas, which in turn become primary determinants of both the pharmacokinetics and pharmacodynamics of circulating nanoparticles. Here, for the first time, the specific binding kinetics of the four major corona forming proteins (human serum albumin, fibrinogen, ApoA1, and polyclonal IgG) are determined for gold nanoparticles (AuNPs). Using a multiplexed surface plasmonic assay, highly reproducible measurements of on rate (k(on)), off rate (k(off)), and disassociation constant (K(D)), in addition to relative amounts of protein binding, are obtained. Dramatic differences in k(on) for individual components are shown as primary determinants of protein affinities, with k(on) ranging over nearly two orders of magnitude for the proteins studied, while k(off) remains within a factor of two for the set. The effect of polyethylene glycol (PEG) modification on plasma component binding is also studied and the effect of PEG length on human serum interaction is characterized through systematic screening of PEG molecular weight (2-30k). The effect of nanoparticle modification on particle targeting is also characterized through study of a hybrid AuNP system.
authors.affiliation: NUSNNI-NanoCore, National University of Singapore, 5A Engineering Drive 1, 11411, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, 117456, Singapore.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Patra
authors.affiliation: Cardiovascular Research Institute, Department of Cardiology, 1E Kent Ridge Road, 119228, Singapore.
authors.forename: Tao
authors.initials: T
authors.lastname: Ding
authors.affiliation: Department of Biomedical Engineering, National University of Singapore, 9 Engineering Drive 1, 117575, Singapore.
authors.forename: Gokce
authors.initials: G
authors.lastname: Engudar
authors.affiliation: Center for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: NUSNNI-NanoCore, National University of Singapore, 5A Engineering Drive 1, 11411, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, 117456, Singapore.
authors.forename: Michal Marcin
authors.initials: MM
authors.lastname: Dykas
authors.affiliation: Center for Biomimetic Sensor Science, School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore.
authors.forename: Bo
authors.initials: B
authors.lastname: Liedberg
authors.affiliation: Department of Biomedical Engineering, National University of Singapore, 9 Engineering Drive 1, 117575, Singapore.
authors.forename: James Chen Yong
authors.initials: JC
authors.lastname: Kah
authors.affiliation: NUSNNI-NanoCore, National University of Singapore, 5A Engineering Drive 1, 11411, Singapore.|NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, 117456, Singapore.|Department of Electrical Engineering, Department of Materials Science and Engineering, Department of Physics, National University of Singapore, 117581, Singapore.
authors.forename: Thirumalai
authors.initials: T
authors.lastname: Venkatesan
authors.affiliation: Cardiovascular Research Institute, Department of Cardiology, 1E Kent Ridge Road, 119228, Singapore.|Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (ASTAR), 8A Biomedical Grove, Immunos, Level 5, 138648, Singapore.
authors.forename: Chester Lee
authors.initials: CL
authors.lastname: Drum
mesh_terms: D001798:Blood Proteins / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D053768:Metal Nanoparticles / Q000737:chemistry*; D044085:Microfluidics; D011092:Polyethylene Glycols / Q000737:chemistry; D000066970:Protein Corona / Q000737:chemistry*; D020349:Surface Plasmon Resonance / Q000379:methods*
chemical_list: D001798:Blood Proteins; D000066970:Protein Corona; D011092:Polyethylene Glycols; D006046:Gold
keywords: high-throughput screening; kinetic studies, drug delivery; protein coronae; surface plasmon resonance