Nanometer- and angstrom-scale characteristics that modulate complement responses to nanoparticles

J Control Release. 2022 Nov:351:432-443. doi: 10.1016/j.jconrel.2022.09.039. Epub 2022 Sep 27.

Abstract

The contribution of the complement system to non-specific host defence and maintenance of homeostasis is well appreciated. Many particulate systems trigger complement activation but the underlying mechanisms are still poorly understood. Activation of the complement cascade could lead to particle opsonisation by the cleavage products of the third complement protein and might promote inflammatory reactions. Antibody binding in a controlled manner and/or sensing of particles by the complement pattern-recognition molecules such as C1q and mannose-binding lectin can trigger complement activation. Particle curvature and spacing arrangement/periodicity of surface functional groups/ligands are two important parameters that modulate complement responses through multivalent engagement with and conformational regulation of surface-bound antibodies and complement pattern-recognition molecules. Thus, a better fundamental understanding of nanometer- and angstrom-scale parameters that modulate particle interaction with antibodies and complement proteins could portend new possibilities for engineering of particulate drug carriers and biomedical platforms with tuneable complement responses and is discussed here.

Keywords: Antibodies; C1q; Complement system; Dendrimers; Factor H; Mannose-binding lectin; Nanoparticles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Complement Activation
  • Complement C1q*
  • Complement System Proteins / metabolism
  • Humans
  • Inflammation
  • Nanoparticles*

Substances

  • Complement C1q
  • Complement System Proteins