Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking.
Complement Activation
/ drug effects
Complement C1q
/ metabolism
Complement System Proteins
/ metabolism
Dendrimers
/ chemistry
Drug Carriers
/ chemistry
Humans
Immunoglobulin M
/ metabolism
Mannose-Binding Lectin
/ metabolism
Mannose-Binding Protein-Associated Serine Proteases
Polyamines
/ chemistry
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 08 2021
11 08 2021
Historique:
received:
08
01
2021
accepted:
06
07
2021
entrez:
12
8
2021
pubmed:
13
8
2021
medline:
24
8
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34381048
doi: 10.1038/s41467-021-24960-6
pii: 10.1038/s41467-021-24960-6
pmc: PMC8357934
doi:
Substances chimiques
Dendrimers
0
Drug Carriers
0
Immunoglobulin M
0
Mannose-Binding Lectin
0
Poly(amidoamine)
0
Polyamines
0
Complement C1q
80295-33-6
Complement System Proteins
9007-36-7
Mannose-Binding Protein-Associated Serine Proteases
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4858Subventions
Organisme : NIAID NIH HHS
ID : R01 AI154959
Pays : United States
Informations de copyright
© 2021. The Author(s).
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