Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking
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Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking. / Wu, Lin Ping; Ficker, Mario; Christensen, Jørn B.; Simberg, Dmitri; Trohopoulos, Panagiotis N.; Moghimi, Seyed M.
I: Nature Communications, Bind 12, Nr. 1, 4858, 12.2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking
AU - Wu, Lin Ping
AU - Ficker, Mario
AU - Christensen, Jørn B.
AU - Simberg, Dmitri
AU - Trohopoulos, Panagiotis N.
AU - Moghimi, Seyed M.
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-021-24960-6
DO - 10.1038/s41467-021-24960-6
M3 - Journal article
C2 - 34381048
AN - SCOPUS:85112345371
VL - 12
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4858
ER -
ID: 279126591