Complement activation by PEGylated single-walled carbon nanotubes is independent of C1q and alternative pathway turnover

Hamad, I., Hunter, A.C., Rutt, Ken, Liu, Z., Dai, H. and Moghimi, S.M. (2008) Complement activation by PEGylated single-walled carbon nanotubes is independent of C1q and alternative pathway turnover Molecular Immunology, 45 (14). pp. 3797-3803. ISSN 0161-5890

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We have investigated the interaction between long circulating poly(ethylene glycol)-stabilized single-walled carbon nanotubes (SWNTs) and the complement system. Aminopoly(ethylene glycol)5000–distearoylphosphatidylethanolamine (aminoPEG5000–DSPE) and methoxyPEG5000–DSPE coated as-grown HIPco SWNTs activated complement in undiluted normal human serum as reflected in significant rises in C4d and SC5b-9 levels, but not the alternative pathway split-product Bb, thus indicating activation exclusively through C4 cleavage. Studies in C2-depleted serum confirmed that PEGylated nanotube-mediated elevation of SC5b-9 was C4b2a convertase-dependent. With the aid of monoclonal antibodies against C1s and human serum depleted from C1q, nanotube-mediated complement activation in C1q-depleted serum was also shown to be independent of classical pathway. Nanotube-mediated C4d elevation in C1q-depleted serum, however, was inhibited by N-acetylglucosamine, Futhan (a broad-spectrum serine protease inhibitor capable of preventing complement activation through all three pathways) and anti-MASP-2 antibodies; this strongly suggests a role for activation of MASP-2 in subsequent C4 cleavage and assembly of C4b2a covertases. Intravenous injection of PEGylated nanotubes in some rats was associated with a significant rise in plasma thromboxane B2 levels, indicative of in vivo nanotube-mediated complement activation. The clinical implications of these observations are discussed.

Item Type: Journal article
Uncontrolled Keywords: Biomaterials; Carbon nanotubes; Complement system; C4; Drug delivery system; Nanomedicine; SC5b-9
Subjects: C000 Biological and Biomedical Sciences > C700 Molecular Biology, Biophysics and Biochemistry
DOI (a stable link to the resource): 10.1016/j.molimm.2008.05.020
Faculties: Faculty of Science and Engineering > School of Pharmacy and Biomolecular Sciences > Chemical Biology
Depositing User: editor spbs
Date Deposited: 04 Aug 2008
Last Modified: 15 Apr 2015 09:40

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