Factor H inhibits complement activation induced by liposomal and micellar drugs and the therapeutic antibody rituximab in vitro

Tamás Mészáros, Ádám I. Csincsi, Barbara Uzonyi, Mario Hebecker, Tamás G. Fülöp, Anna Erdei, János Szebeni, Mihály Józsi

Research output: Article

13 Citations (Scopus)

Abstract

Hypersensitivity reactions to particulate drugs can partly be caused by complement activation and represent a major complication during intravenous application of nanomedicines. Several liposomal and micellar drugs and carriers, and therapeutic antibodies, were shown to activate complement and induce complement activation-related pseudoallergy (CARPA) in model animals. To explore the possible use of the natural complement inhibitor factor H (FH) against CARPA, we examined the effect of FH on complement activation induced by CARPAgenic drugs. Exogenous FH inhibited complement activation induced by the antifungal liposomal Amphotericin-B (AmBisome), the widely used solvent of anticancer drugs Cremophor EL, and the anticancer monoclonal antibody rituximab in vitro. An engineered form of FH (mini-FH) was more potent inhibitor of Ambisome-, Cremophor EL- and rituximab-induced complement activation than FH. The FH-related protein CFHR1 had no inhibitory effect. Our data suggest that FH or its derivatives may be considered in the pharmacological prevention of CARPA.

Original languageEnglish
Pages (from-to)1023-1031
Number of pages9
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume12
Issue number4
DOIs
Publication statusPublished - máj. 1 2016

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ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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