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

Author

Listed:
  • Nicolas Bertrand

    (Massachusetts Institute of Technology (MIT)
    Université Laval)

  • Philippe Grenier

    (Université Laval)

  • Morteza Mahmoudi

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Eliana M. Lima

    (Massachusetts Institute of Technology (MIT)
    Federal University of Goiás)

  • Eric A. Appel

    (Massachusetts Institute of Technology (MIT)
    Stanford University)

  • Flavio Dormont

    (Massachusetts Institute of Technology (MIT))

  • Jong-Min Lim

    (Massachusetts Institute of Technology
    Soonchunhyang University)

  • Rohit Karnik

    (Massachusetts Institute of Technology)

  • Robert Langer

    (Massachusetts Institute of Technology (MIT)
    MIT)

  • Omid C. Farokhzad

    (Brigham and Women’s Hospital, Harvard Medical School
    King Abdulaziz University)

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.

Suggested Citation

  • Nicolas Bertrand & Philippe Grenier & Morteza Mahmoudi & Eliana M. Lima & Eric A. Appel & Flavio Dormont & Jong-Min Lim & Rohit Karnik & Robert Langer & Omid C. Farokhzad, 2017. "Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics," Nature Communications, Nature, vol. 8(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00600-w
    DOI: 10.1038/s41467-017-00600-w
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    Cited by:

    1. Mingyang Li & Xinyang Jin & Tao Liu & Feng Fan & Feng Gao & Shuang Chai & Lihua Yang, 2022. "Nanoparticle elasticity affects systemic circulation lifetime by modulating adsorption of apolipoprotein A-I in corona formation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Kai Liu & Ralf Nilsson & Elisa Lázaro-Ibáñez & Hanna Duàn & Tasso Miliotis & Marie Strimfors & Michael Lerche & Ana Rita Salgado Ribeiro & Johan Ulander & Daniel Lindén & Anna Salvati & Alan Sabirsh, 2023. "Multiomics analysis of naturally efficacious lipid nanoparticle coronas reveals high-density lipoprotein is necessary for their function," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Yunqiu Miao & Lijun Li & Ying Wang & Jiangyue Wang & Yihan Zhou & Linmiao Guo & Yanqi Zhao & Di Nie & Yang Zhang & Xinxin Zhang & Yong Gan, 2024. "Regulating protein corona on nanovesicles by glycosylated polyhydroxy polymer modification for efficient drug delivery," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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