[Application of novel drug delivery system, fusogenic liposome, for cancer therapy]

Over the past decade, many studies concerning novel anti-cancer therapies have been reported. It has been occasionally noted that a powerful anti-cancer drug, especially one whose target is the cytoplasm or cell nucleus, does not work due to the low permeability across a plasma membrane, degradation by lysosomal enzymes through an endocytosis-dependent pathway, and other reasons. Thus, several approaches using drug delivery systems (DDS) are focused on overcoming these difficulties, eventually leading to the induction of maximal ability of anti-cancer drug. In this respect, we have developed a new paradigm for cancer therapy using a novel drug delivery system, fusogenic liposome. Fusogenic liposomes are composed of the ultraviolet-inactivated Sendai virus and conventional liposomes. Fusogenic liposomes effectively and directly deliver their encapsulated contents into the cytoplasm using a fusion mechanism of the Sendai virus, whereas conventional liposomes are taken up by endocytosis. Thus, fusogenic liposome is a good candidate as a vehicle to deliver drugs into the cytoplasm in an endocytosis-independent manner. In this report, we show the feasibility of fusogenic liposome as a delivery vehicle for anti-cancer drugs using a fragment A of diphtheria toxin as an anti-cancer reagent. We also demonstrate the application of fusogenic liposome for cancer gene therapy and cancer vaccines using a TNF-alpha-expression plasmid and a chicken egg ovalbumin, respectively.