Статья

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

Nicolas BertrandWilfrid Laurier UniversityP. GrenierFaculty of Pharmacy, CHU de Quebec Research Center, Université Laval, 2705 Laurier Blvd, Québec, Canada, G1V 4G2Morteza MahmoudiCenter for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USAEliana Martins LimaDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), 500 Main Street, Building 76-661, Cambridge, MA, 02139, USAEric A. AppelDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), 500 Main Street, Building 76-661, Cambridge, MA, 02139, USAFlavio DormontDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), 500 Main Street, Building 76-661, Cambridge, MA, 02139, USAJong‐Min LimDepartment of Chemical Engineering, Soonchunhyang University, 22 Soonchunhyang-ro, Shinchang-myeon, Asan-si, Chungcheongnam-do, 31538, KoreaRohit KarnikDepartment of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USARóbert LangerDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (MIT), 500 Main Street, Building 76-661, Cambridge, MA, 02139, USAOmid C. FarokhzadCenter for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA. [email protected]

2017en

ABI

Аннотация

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 nm 2 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.

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Идентификаторы

DOI: 10.1038/s41467-017-00600-w

Цитирования и источники

Цитирований: 2Использованных источников: 0

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