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

I. Hamad, A.C. Hunter, Ken Rutt, Z. Liu, H. Dai, S.M. Moghimi

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)3797-3803
Number of pages7
JournalMolecular Immunology
Volume45
Issue number14
DOIs
Publication statusPublished - Aug 2008

Keywords

  • Biomaterials
  • Carbon nanotubes
  • Complement system
  • C4
  • Drug delivery system
  • Nanomedicine
  • SC5b-9

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