Combating Complement's Deleterious Effects on Nanomedicine by Conjugating Complement Regulatory Proteins to Nanoparticles

Bibliographische Detailangaben
Veröffentlicht in:	Advanced materials (Deerfield Beach, Fla.). - 1998. - 34(2022), 8 vom: 19. Feb., Seite e2107070
1. Verfasser:	Wang, Zhicheng (VerfasserIn)
Weitere Verfasser:	Hood, Elizabeth D, Nong, Jia, Ding, Jing, Marcos-Contreras, Oscar A, Glassman, Patrick M, Rubey, Kathryn M, Zaleski, Michael, Espy, Carolann L, Gullipali, Damodara, Miwa, Takashi, Muzykantov, Vladimir R, Song, Wen-Chao, Myerson, Jacob W, Brenner, Jacob S
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2022
Zugriff auf das übergeordnete Werk:	Advanced materials (Deerfield Beach, Fla.)
Schlagworte:	Journal Article C3 CARPA anaphylaxis complement nanomedicine nanoparticles opsonization reticulo-endothelial system Complement C3 mehr... Complement Factor H 80295-65-4 Fibrinogen 9001-32-5

Beschreibung
Zusammenfassung:	© 2022 Wiley-VCH GmbH. Complement opsonization is among the biggest challenges facing nanomedicine. Nearly instantly after injection into blood, nanoparticles are opsonized by the complement protein C3, leading to clearance by phagocytes, fouling of targeting moieties, and release of anaphylatoxins. While surface polymers such as poly(ethylene glycol) (PEG) partially decrease complement opsonization, most nanoparticles still suffer from extensive complement opsonization, especially when linked to targeting moieties. To ameliorate the deleterious effects of complement, two of mammals' natural regulators of complement activation (RCAs), Factors H and I, are here conjugated to the surface of nanoparticles. In vitro, Factor H or I conjugation to PEG-coated nanoparticles decrease their C3 opsonization, and markedly reduce nanoparticle uptake by phagocytes. In an in vivo mouse model of sepsis-induced lung injury, Factor I conjugation abrogates nanoparticle uptake by intravascular phagocytes in the lungs, allowing the blood concentration of the nanoparticle to remain elevated much longer. For nanoparticles targeted to the lung's endothelium by conjugation to anti-ICAM antibodies, Factor I conjugation shifts the cell-type distribution away from phagocytes and toward endothelial cells. Finally, Factor I conjugation abrogates the severe anaphylactoid responses common to many nanoparticles, preventing systemic capillary leak and preserving blood flow to visceral organs and the brain. Thus, conjugation of RCAs, like Factor I, to nanoparticles is likely to help in nanomedicine's long battle against complement, improving several key parameters critical for clinical success
Beschreibung:	Date Completed 31.03.2022 Date Revised 16.09.2023 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-4095
DOI:	10.1002/adma.202107070