Nanoparticles (NPs) that are exposed to blood are coated with an assortment of proteins that establish their biological identity by forming the interface between the NP and the cells and tissues of the body. The biological relevance of this protein corona is often overlooked during toxicological assessments of NPs. However, accurate interpretation of biological outcomes following exposure to NPs, including activation of coagulation, opsonization of pathogens, and cellular phagocytosis, must take this adsorbed proteome into account. In this study, we examined protein coronas on the surface of five poly(acrylic acid) (PAA) metal-oxide NPs (TiO2, CeO2, Fe2O3, ZnO, and PAA-capsules) following exposure to human plasma for key markers of various host response pathways, including humoral immunity and coagulation. We also evaluated the impacts of pre-exposing serum proteins to PAA-NPs on the opsonization and phagocytosis of bacteria by two immune cell lines. Results demonstrated that each PAA-NP type adsorbed a unique profile of blood proteins and that protein-coated PAA-NPs significantly inhibited human plasma coagulation with PAA-zinc oxide NPs and their associated proteome fully abrogating clotting. Protein-coated PAA-NPs also resulted in a 50% increase in phagocytic activity of RBL-2H3 cells and a 12.5% increase in phagocytic activity in the RAW 264.7 cell line. We also identified numerous structural, coagulation, and immune-activating proteins in the adsorbed protein corona, which resulted in altered biological function. Overall, our findings demonstrate that the formation of protein coronas on the surface of NPs plays an important role in directing the biological outcomes of opsonization, cell phagocytosis, and blood coagulation.
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September 2020
Research Article|
September 21 2020
Polymer-coated nanoparticle protein corona formation potentiates phagocytosis of bacteria by innate immune cells and inhibits coagulation in human plasma
Special Collection:
Special Topic Collection: Protein Corona at Nanointerfaces
Van A. Ortega
;
Van A. Ortega
a)
1
Department of Biological Sciences, University of Alberta
, Edmonton, Alberta T6G 2E9, Canada
a)Author to whom correspondence should be addressed: [email protected]
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Markian S. Bahniuk
;
Markian S. Bahniuk
2
National Research Council of Canada Nanotechnology
, Edmonton, Alberta T6G 2M9, Canada
3
Department of Biomedical Engineering, University of Alberta
, Edmonton, Alberta T6G 2V2, Canada
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Sharyar Memon
;
Sharyar Memon
1
Department of Biological Sciences, University of Alberta
, Edmonton, Alberta T6G 2E9, Canada
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Larry D. Unsworth
;
Larry D. Unsworth
2
National Research Council of Canada Nanotechnology
, Edmonton, Alberta T6G 2M9, Canada
3
Department of Biomedical Engineering, University of Alberta
, Edmonton, Alberta T6G 2V2, Canada
4
Department of Chemical and Materials Engineering, University of Alberta
, Edmonton, Alberta T6G 1H9, Canada
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James L. Stafford
;
James L. Stafford
1
Department of Biological Sciences, University of Alberta
, Edmonton, Alberta T6G 2E9, Canada
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Greg G. Goss
Greg G. Goss
b)
1
Department of Biological Sciences, University of Alberta
, Edmonton, Alberta T6G 2E9, Canada
2
National Research Council of Canada Nanotechnology
, Edmonton, Alberta T6G 2M9, Canada
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a)Author to whom correspondence should be addressed: [email protected]
b)
Electronic mail: [email protected]
Note: This paper is part of the Biointerphases Special Topic Collection on Protein Corona at Nanointerfaces.
Biointerphases 15, 051003 (2020)
Article history
Received:
June 11 2020
Accepted:
August 24 2020
Citation
Van A. Ortega, Markian S. Bahniuk, Sharyar Memon, Larry D. Unsworth, James L. Stafford, Greg G. Goss; Polymer-coated nanoparticle protein corona formation potentiates phagocytosis of bacteria by innate immune cells and inhibits coagulation in human plasma. Biointerphases 1 September 2020; 15 (5): 051003. https://doi.org/10.1116/6.0000385
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