発がんと突然変異誘発のジャーナル

概要

Negatively Charged Cell Membranes-Targeted Highly Selective Chemotherapy with Cationic Hybrid Liposomes against Colorectal Cancer In Vitro and In Vivo

Ichihara H, Motomura M and Matsumoto Y

Cationic hybrid liposomes (CHL) composed of 87 mol% L-α-dimyristoylphosphatidylcholine (DMPC), 5 mol% polyoxyethylene (21) dodecyl ether (C12(EO)21) and 8 mol% O,O’-ditetradecanoyl-N-(α–trimethylammonioacetyl) diethanolamine chloride (2C14ECl) were prepared by the method of sonication. A clear solution of CHL having a hydrodynamic diameter of 100 nm could be maintained over 4 weeks. The IC50 value of CHL on the growth of human colorectal cancer (CRC; HCT116) cells was remarkably smaller than that of the DMPC liposomes. Immediate fusion of CHL including NBDPC into HCT116 cell membranes was confirmed using a confocal laser and total internal reflection fluorescence (TIRF) microscope without affecting normal colon (CCD-33Co) cells. Activation of caspases for apoptosis of HCT116 cells induced by CHL was verified on the basis of fluorescence microscopy. Carcinoma HCT116 cells have lower membrane potential compared to normal CCD-33Co cells, since negatively charged PS and GM1 in HCT116 cells increased compared with that of normal CCD-33Co. Therapeutic effects of CHL were obtained in xenograft mouse models of CRC in vivo. Induction of apoptosis in tumor of xenograft mouse model of human CRC treated with CHL was observed in micrographs of tissue section on the basis of TUNEL method. Furthermore, no severe side effects of CHL were observed in toxicity tests using normal mice.