Chemotherapy using hybrid liposomes along with induction of apoptosis.

We have produced hybrid liposomes (HL) which can be prepared by ultrasonicating a mixture of dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene(23)dodecyl ether in a buffer solution. The fifty-percent inhibitory concentration (IC50) of HL on the growth of human B lymphoma (RAJI) cells in vitro was determined. The IC50 of HL on the growth of RAJI cells was one half of that of DMPC liposomes. Induction of apoptosis by HL in RAJI cells was verified on the basis of flow cytometric analysis, agarose gel electrophoresis and fluorescence microscopy. Apoptotic DNA was observed in RAJI cells treated with HL. Fluorescence micrographs of RAJI cells after adding HL indicated the induction of apoptosis. The therapeutic effects of HL in vivo were examined using SCID mice inoculated with RAJI cells. Markedly prolonged survival of mice was obtained after treatment with HL. No adverse effects were observed in normal rats in toxicity tests carried out with HL. Clinical applications of HL for patients were examined after the approval of the Bioethics Committee. Remarkable reduction of a solid tumor and prolonged survival for one patient with advanced lymphoma were attained after treatment using HL. Chemotherapy with drug-free HL was established without any side effects for the first time.