title: Role of Albumin in the Formation and Stabilization of Nanoparticle Aggregates in Serum Studied by Continuous Photon Correlation Spectroscopy and Multiscale Computer Simulations.
abstract: Recently, small (<5 nm diameter) nanoparticles (NPs) have shown improvedin vivobiocompatibility compared to that of larger (>10 nm) NPs. However, the fate of small NPs under physiological conditions is poorly understood and remains unexplored. Here, the long-term aggregation behavior of gold nanoparticles (AuNPs) exposed to serum proteins in a near-physiological setup is studied using continuous photon correlation spectroscopy and computer simulations. It is found that the medium, temperature, and NP concentration affect the aggregation of AuNPs, but the observed aggregates are much smaller than previously reported. Simulations show that a single layer of albumin is deposited on the NP surface, but the properties of the aggregates (size, shape, and internal structure) depend critically on the charge distribution on the proteins, which changes with the conditions of the solution. These results explain the seemingly conflicting data reported in the literature regarding the size of aggregates and the morphology of the albumin corona. The simulations suggest that controlling the concentration of NPs as well as the pH and ionic strength of the solution prior to intravenous administration may help to preserve properties of the functionalized NPs in the bloodstream.
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors.forename: Ashwinkumar A
authors.initials: AA
authors.lastname: Bhirde
authors.affiliation: Center for Molecular Modeling, Division of Computational Bioscience, CIT, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Hassan
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors.forename: Erick
authors.initials: E
authors.lastname: Harr
authors.affiliation: Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen