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Lookup NU author(s): Professor Moein MoghimiORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.Effective inhibition of the complement system is needed to prevent the accelerated clearance of nanomaterials by complement cascade and inflammatory responses. Here we show that a fusion construct consisting of human complement receptor 2 (CR2) (which recognizes nanosurface-deposited complement 3 (C3)) and complement receptor 1 (CR1) (which blocks C3 convertases) inhibits complement activation with picomolar to low nanomolar efficacy on many types of nanomaterial. We demonstrate that only a small percentage of nanoparticles are randomly opsonized with C3 both in vitro and in vivo, and CR2-CR1 immediately homes in on this subpopulation. Despite rapid in vivo clearance, the co-injection of CR2-CR1 in rats, or its mouse orthologue CR2-Crry in mice, with superparamagnetic iron oxide nanoparticles nearly completely blocks complement opsonization and unwanted granulocyte/monocyte uptake. Furthermore, the inhibitor completely prevents lethargy caused by bolus-injected nanoparticles, without inducing long-lasting complement suppression. These findings suggest the potential of the targeted complement regulators for clinical evaluation.
Author(s): Li Y, Jacques S, Gaikwad H, Wang G, Banda NK, Holers VM, Scheinman RI, Tomlinson S, Moghimi SM, Simberg D
Publication type: Article
Publication status: Published
Journal: Nature Nanotechnology
Year: 2023
Pages: epub ahead of print
Online publication date: 05/10/2023
Acceptance date: 25/08/2023
Date deposited: 25/01/2024
ISSN (print): 1748-3387
ISSN (electronic): 1748-3395
Publisher: Nature Research
URL: https://doi.org/10.1038/s41565-023-01514-z
DOI: 10.1038/s41565-023-01514-z
ePrints DOI: 10.57711/nnr1-2k52
PubMed id: 37798566
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