Characterization of a novel liposome based therapy to reduce complement deposition on cell membranes

Abstract

Excessive complement activation following ischemia and reperfusion (IR) induces endothelial cell injury, altering vascular and endothelial barrier function causing tissue dysfunction. To mitigate IR response various systemic anti‐complement therapies have been tried. Recently, we developed a local therapy that uses biotinylated fusogenic lipid vesicles (BioFLVs) to incorporate biotin tethers onto cell membranes, which then bind to therapeutic fusion proteins containing streptavidin (SA) resulting in decoration of cell membranes. Alteration of formulation, concentration and duration of incubation of BioFLVs were conducted to demonstrate the ability of the system to modulate biotin tether incorporation. A rat hind limb model was used to demonstrate the efficacy of this system for 48 h of reperfusion. The feasibility of a BioFLV‐based anti‐complement therapy was tested in human ovarian carcinoma (SKOV3) cells using SA fused with vaccinia virus complement control protein (SA‐VCP), a C3 convertase inhibitor. To activate complement cells were treated with a SKOV‐3‐specific antibody (trastuzumab) and incubated in human serum. Decoration of cells with SA‐VCP effectively reduced complement deposition. We conclude that BioFLV‐mediated decoration of cell membranes with anti‐complement proteins has potential to reduce IR‐mediated complement injury in transplantated or replanted tissues.