Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics

Nicolas Bertrand, Philippe Grenier, Morteza Mahmoudi, Eliana M. Lima, Eric A. Appel, Flavio Dormont, Jong-Min Lim, Rohit Karnik, Robert Langer and Omid C. Farokhzad ()
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Nicolas Bertrand: Massachusetts Institute of Technology (MIT)
Philippe Grenier: Université Laval
Morteza Mahmoudi: Brigham and Women’s Hospital, Harvard Medical School
Eliana M. Lima: Massachusetts Institute of Technology (MIT)
Eric A. Appel: Massachusetts Institute of Technology (MIT)
Flavio Dormont: Massachusetts Institute of Technology (MIT)
Jong-Min Lim: Massachusetts Institute of Technology
Rohit Karnik: Massachusetts Institute of Technology
Robert Langer: Massachusetts Institute of Technology (MIT)
Omid C. Farokhzad: Brigham and Women’s Hospital, Harvard Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: Abstract In vitro incubation of nanomaterials with plasma offer insights on biological interactions, but cannot fully explain the in vivo fate of nanomaterials. Here, we use a library of polymer nanoparticles to show how physicochemical characteristics influence blood circulation and early distribution. For particles with different diameters, surface hydrophilicity appears to mediate early clearance. Densities above a critical value of approximately 20 poly(ethylene glycol) chains (MW 5 kDa) per 100 nm2 prolong circulation times, irrespective of size. In knockout mice, clearance mechanisms are identified for nanoparticles with low and high steric protection. Studies in animals deficient in the C3 protein showed that complement activation could not explain differences in the clearance of nanoparticles. In nanoparticles with low poly(ethylene glycol) coverage, adsorption of apolipoproteins can prolong circulation times. In parallel, the low-density-lipoprotein receptor plays a predominant role in the clearance of nanoparticles, irrespective of poly(ethylene glycol) density. These results further our understanding of nanopharmacology.

Date: 2017
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DOI: 10.1038/s41467-017-00600-w

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