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ACS Nano. 2019 May 28;13(5):4980-4991. doi: 10.1021/acsnano.9b00552. Epub 2019 Apr 18.

Link between Low-Fouling and Stealth: A Whole Blood Biomolecular Corona and Cellular Association Analysis on Nanoengineered Particles.

Author information

1
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and the Department of Chemical Engineering , The University of Melbourne , Parkville , Victoria 3010 , Australia.
2
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity , The University of Melbourne , Parkville , Victoria 3010 , Australia.
3
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology , Parkville , Victoria 3010 , Australia.
4
Systems Biology Laboratory, School of Mathematics and Statistics, and the Department of Biomedical Engineering , The University of Melbourne , Parkville , Victoria 3010 , Australia.
5
Bio21 Molecular Science and Biotechnology Institute , The University of Melbourne , Parkville , Victoria 3010 , Australia.

Abstract

Upon exposure to human blood, nanoengineered particles interact with a multitude of plasma components, resulting in the formation of a biomolecular corona. This corona modulates downstream biological responses, including recognition by and association with human immune cells. Considerable research effort has been directed toward the design of materials that can demonstrate a low affinity for various proteins (low-fouling materials) and materials that can exhibit low association with human immune cells (stealth materials). An implicit assumption common to bio-nano research is that nanoengineered particles that are low-fouling will also exhibit stealth. Herein, we investigated the link between the low-fouling properties of a particle and its propensity for stealth in whole human blood. High-fouling mesoporous silica (MS) particles and low-fouling zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) particles were synthesized, and their interaction with blood components was assessed before and after precoating with serum albumin, immunoglobulin G, or complement protein C1q. We performed an in-depth proteomics characterization of the biomolecular corona that both identifies specific proteins and measures their relative abundance. This was compared with observations from a whole blood association assay that identified with which cell type each particle system associates. PMPC-based particles displayed reduced association both with cells and with serum proteins compared with MS-based particles. Furthermore, the enrichment of specific proteins within the biomolecular corona was found to correlate with association with specific cell types. This study demonstrates how the low-fouling properties of a material are indicative of its stealth with respect to immune cell association.

KEYWORDS:

biomolecular corona; cellular association; human whole blood assay; low-fouling; stealth

PMID:
30998312
DOI:
10.1021/acsnano.9b00552

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