人工膜および細胞膜の揺らぎとがん治療

Abstract

“Molecular science of fluctuations toward biological functions ” should be important for understanding the origin of life. Membrane-fluctuations of tumor cells are very different from those of normal cells. In general, the membranes of tumor cells are more fluid as compared with normal cells. We have produced hybrid liposomes (HL) which can be prepared by sonication of vesicular and micellar molecules in a buffer solution. The physical properties of HL such as size, shape, membrane fluidity, and the temperature of phase separation can be controlled by changing the constituents and compositional ratio. The uniform and stable structure of HL-n composed of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenedodecyl ether (C12(EO)n : n = 21~25) with a diameter of 80 nm was revealed. The remarkable inhibitory effects of HL on the growth of various tumor cells were attained in vitro. The induction of apoptosis by HL was obtained and the pathway was elucidated. Hybirid liposomes fused and accumulated in tumor cell membranes, and the apoptotic signal firstly pathed through mitochondria, caspase-9, and caspase-3, secondly through Fas, caspase-8, caspase-3 and then reached the nucleus. A good correlation between the membrane fluidity of HL and inhibitory effects of HL for tumor cells was obtained. Significantly chemotherapeutic effects were obtained using mice model of carcinoma after the treatment with HL without any drug in vivo. There were no abnormal findings on normal rats after administering HL on the basis of chronic toxicity tests. In clinical applications, prolonged survival was attained in patients with lymphoma after the intravenous injection of HL without any side effect after the approval of the bioethics committee. The membrane targeted chemotherapy with drug-free HL was established without any side effects for the first time.