Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking

Nat Commun. 2021 Aug 11;12(1):4858. doi: 10.1038/s41467-021-24960-6.


Complement is an enzymatic humoral pattern-recognition defence system of the body. Non-specific deposition of blood biomolecules on nanomedicines triggers complement activation through the alternative pathway, but complement-triggering mechanisms of nanomaterials with dimensions comparable to or smaller than many globular blood proteins are unknown. Here we study this using a library of <6 nm poly(amido amine) dendrimers bearing different end-terminal functional groups. Dendrimers are not sensed by C1q and mannan-binding lectin, and hence do not trigger complement activation through these pattern-recognition molecules. While, pyrrolidone- and carboxylic acid-terminated dendrimers fully evade complement response, and independent of factor H modulation, binding of amine-terminated dendrimers to a subset of natural IgM glycoforms triggers complement activation through lectin pathway-IgM axis. These findings contribute to mechanistic understanding of complement surveillance of dendrimeric materials, and provide opportunities for dendrimer-driven engineering of complement-safe nanomedicines and medical devices.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Complement Activation* / drug effects
  • Complement C1q / metabolism
  • Complement System Proteins / metabolism*
  • Dendrimers / chemistry
  • Dendrimers / metabolism*
  • Dendrimers / pharmacology
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism
  • Drug Carriers / pharmacology
  • Humans
  • Immunoglobulin M / metabolism*
  • Mannose-Binding Lectin / metabolism
  • Mannose-Binding Protein-Associated Serine Proteases
  • Polyamines / chemistry
  • Polyamines / metabolism
  • Polyamines / pharmacology


  • Dendrimers
  • Drug Carriers
  • Immunoglobulin M
  • Mannose-Binding Lectin
  • Poly(amidoamine)
  • Polyamines
  • Complement C1q
  • Complement System Proteins
  • Mannose-Binding Protein-Associated Serine Proteases