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

Lookup NU author(s): Professor Moein MoghimiORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2021, The Author(s).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 metadata

Author(s): Wu L-P, Ficker M, Christensen JB, Simberg D, Trohopoulos PN, Moghimi SM

Publication type: Article

Publication status: Published

Journal: Nature Communications

Year: 2021

Volume: 12

Issue: 1

Online publication date: 11/08/2021

Acceptance date: 06/07/2021

Date deposited: 25/08/2021

ISSN (electronic): 2041-1723

Publisher: Nature Research

URL: https://doi.org/10.1038/s41467-021-24960-6

DOI: 10.1038/s41467-021-24960-6

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