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Lookup NU author(s): Professor Moein MoghimiORCiD
This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2019.
For re-use rights please refer to the publisher's terms and conditions.
© 2019, The Author(s), under exclusive licence to Springer Nature Limited. Deposition of complement factors (opsonization) on nanoparticles may promote clearance from the blood by macrophages and trigger proinflammatory responses, but the mechanisms regulating the efficiency of complement activation are poorly understood. We previously demonstrated that opsonization of superparamagnetic iron oxide (SPIO) nanoworms with the third complement protein (C3) was dependent on the biomolecule corona of the nanoparticles. Here we show that natural antibodies play a critical role in C3 opsonization of SPIO nanoworms and a range of clinically approved nanopharmaceuticals. The dependency of C3 opsonization on immunoglobulin binding is almost universal and is observed regardless of the complement activation pathway. Only a few surface-bound immunoglobulin molecules are needed to trigger complement activation and opsonization. Although the total amount of plasma proteins adsorbed on nanoparticles does not determine C3 deposition efficiency, the biomolecule corona per se enhances immunoglobulin binding to all nanoparticle types. We therefore show that natural antibodies represent a link between biomolecule corona and C3 opsonization, and may determine individual complement responses to nanomedicines.
Author(s): Vu VP, Gifford GB, Chen F, Benasutti H, Wang G, Groman EV, Scheinman R, Saba L, Moghimi SM, Simberg D
Publication type: Article
Publication status: Published
Journal: Nature Nanotechnology
Year: 2019
Volume: 14
Pages: 260-268
Online publication date: 14/01/2019
Acceptance date: 05/12/2018
Date deposited: 07/12/2020
ISSN (print): 1748-3387
ISSN (electronic): 1748-3395
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41565-018-0344-3
DOI: 10.1038/s41565-018-0344-3
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