Complement proteins bind to nanoparticle protein corona and undergo dynamic exchange in vivo

Fangfang Chen, Guankui Wang, James I. Griffin, Barbara Brenneman, Nirmal K. Banda, V. Michael Holers, Donald S. Backos, Linping Wu, Seyed Moein Moghimi, Dmitri Simberg

Research output: Contribution to journalArticle

220 Scopus citations

Abstract

When nanoparticles are intravenously injected into the body, complement proteins deposit on the surface of nanoparticles in a process called opsonization. These proteins prime the particle for removal by immune cells and may contribute toward infusion-related adverse effects such as allergic responses. The ways complement proteins assemble on nanoparticles have remained unclear. Here, we show that dextran-coated superparamagnetic iron oxide core-shell nanoworms incubated in human serum and plasma are rapidly opsonized with the third complement component (C3) via the alternative pathway. Serum and plasma proteins bound to the nanoworms are mostly intercalated into the nanoworm shell. We show that C3 covalently binds to these absorbed proteins rather than the dextran shell and the protein-bound C3 undergoes dynamic exchange in vitro. Surface-bound proteins accelerate the assembly of the complement components of the alternative pathway on the nanoworm surface. When nanoworms pre-coated with human plasma were injected into mice, C3 and other adsorbed proteins undergo rapid loss. Our results provide important insight into dynamics of protein adsorption and complement opsonization of nanomedicines.

Original languageEnglish (US)
Pages (from-to)387-393
Number of pages7
JournalNature Nanotechnology
Volume12
Issue number4
DOIs
StatePublished - May 1 2017

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrical and Electronic Engineering

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