Dendrimer end-terminal motif-dependent evasion of complement activation

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

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.

Reference
Wu, L. P., Ficker, M., Christensen, J. B., Simberg, D., Trohopoulos, P. N., & Moghimi, S. M. (2021). Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking. Nature communications, 12(1), 1-13.

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