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Cited by 708Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsDendrimers and Hyperbranched Polymers

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

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Bertrand, Nicolas, Grenier, Philippe, Mahmoudi, Morteza, Lima, Eliana M., Appel, Eric A., Dormont, Flavio, Lim, Jong-Min, Karnik, Rohit +2 more·2017·Nature Communications
DOI 10.1038/s41467-017-00600-wPMC PMC5626760
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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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  • Exchangeable apolipoproteins (such as ApoA, C, and E) are found in protein coronas formed on the surface of a variety of drug delivery systems.

    “Exchangeable apolipoproteins (such as ApoA, C, and E) that can direct the transport of lipids through lymphatic and circulatory systems have been found in protein coronas formed on the surface of a variety of drug delivery systems15–17.”

    From Brain-targeted drug delivery by manipulating protein corona functions (2019) · cites this paper as [17]

    The Results (‘In vivo protein corona’; page unavailable) report apolipoproteins in coronas on metal, lipid, and polymer nanoparticles, and the study identifies ApoE on its polymeric nanoparticles. The passages do not specifically identify ApoA or ApoC in those coronas, so those examples are not established by this source. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Bertrand, N., Grenier, P., Mahmoudi, M., Lima, E. M., Appel, E. A., Dormont, F., Lim, J.-M., Karnik, R., Langer, R., & Farokhzad, O. C.
Affiliations
  • Université Laval (CA)
  • Brigham and Women's Hospital (US)
  • Koch Institute for Integrative Cancer Research At MIT (US)
  • Soonchunhyang University (KR)
  • Massachusetts Institute of Technology (US)
Corresponding author
Farokhzad, Omid C.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-10-03
Volume
8
Issue
1
Pages
777-777
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-017-00600-w
PMC
PMC5626760
OpenAlex
W2757272801
Cited by
708
References
5
Citations by year
2026: 74 · 2025: 60 · 2024: 65 · 2023: 75 · 2022: 81 · 2021: 94 · 2020: 113 · 2019: 77 · 2018: 68 · 2017: 1
FWCI
25.53
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Prostate Cancer Foundation
  • Wellcome Trust
  • Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology (P30-CA14051)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (2014‐0)
  • Canadian Institutes of Health Research
  • Natural Sciences and Engineering Research Council of Canada
  • National Heart, Lung, and Blood Institute (HHSN268201000045C)
  • National Cancer Institute (U54CA151884, CA14051, CA151884, P30-CA-14051)
  • National Institute of Biomedical Imaging and Bioengineering (EB015419-01, R01EB015419, EB015419)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
protein corona, polymeric nanoparticles, pharmacokinetics, nanoparticle clearance, blood circulation, surface hydrophilicity, particle size, LDL receptor, complement activation, knockout mice, nanopharmacology
MeSH terms
Protein Corona, Adsorption, Animals, Apolipoproteins, Complement Activation, Complement C3, Male, Particle Size, Polyethylene Glycols, Receptors, LDL, Surface Properties, Drug Delivery Systems, Rats, Sprague-Dawley, Mice, Knockout, Mice, Rats, Nanoparticles, Hydrophobic and Hydrophilic Interactions

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