Immunoglobulin deposition on biomolecule corona determines complement opsonization efficiency of preclinical and clinical nanoparticles

Nat Nanotechnol. 2019 Mar;14(3):260-268. doi: 10.1038/s41565-018-0344-3. Epub 2019 Jan 14.


Deposition of complement factors (opsonization) on nanoparticles may promote clearance from the blood by macrophages and trigger proinflammatory responses, but the mechanisms regulating the efficiency of complement activation are poorly understood. We previously demonstrated that opsonization of superparamagnetic iron oxide (SPIO) nanoworms with the third complement protein (C3) was dependent on the biomolecule corona of the nanoparticles. Here we show that natural antibodies play a critical role in C3 opsonization of SPIO nanoworms and a range of clinically approved nanopharmaceuticals. The dependency of C3 opsonization on immunoglobulin binding is almost universal and is observed regardless of the complement activation pathway. Only a few surface-bound immunoglobulin molecules are needed to trigger complement activation and opsonization. Although the total amount of plasma proteins adsorbed on nanoparticles does not determine C3 deposition efficiency, the biomolecule corona per se enhances immunoglobulin binding to all nanoparticle types. We therefore show that natural antibodies represent a link between biomolecule corona and C3 opsonization, and may determine individual complement responses to nanomedicines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Complement C3 / metabolism
  • Complement System Proteins / metabolism*
  • Female
  • Humans
  • Immunoglobulin G / metabolism
  • Immunoglobulins / metabolism*
  • Liposomes
  • Male
  • Middle Aged
  • Models, Biological
  • Nanoparticles / chemistry*
  • Opsonin Proteins / metabolism*
  • Protein Binding
  • Protein Corona / chemistry*


  • Complement C3
  • Immunoglobulin G
  • Immunoglobulins
  • Liposomes
  • Opsonin Proteins
  • Protein Corona
  • Complement System Proteins