Work

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

Year: 2021

Type: article

Abstract: 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.

Source: Nature Communications

DOI: 10.1038/s41467-021-24960-6

Authors: Lin-Ping Wu, Mario Ficker, Jørn B. Christensen, Dmitri Simberg, Panagiotis N. Trohopoulos, Seyed M. Moghimi