Chemotherapy with hybrid liposomes for human breast tumors along with apoptosis in vivo.

Hybrid liposomes (HL-n) can be prepared by dissolving both vesicular and micellar molecules in buffer solution with ultrasonication. A clear solution of HL-n composed of 95 mol% dimyristoylphosphatidylcholine (DMPC) and 5 mol% polyoxyethylenedodecyl ether (C(12)(EO)(n), n=21 and 25) having hydrodynamic diameter of 100 nm could be kept over 1 month on the basis of dynamic light scattering measurements was obtained. (1) Increases of fusion and accumulation of HL-n including NBDPC as a fluorescence probe into human breast tumor (MDA-MB-453) cell membranes were observed. (2) Reduction of mitochondrial membrane potential and activation of caspase-8, caspase-9, and caspase-3 were observed, indicating that apoptotic signal by HL-n should pass through mitochondria and these caspases. (3) Remarkable reduction of tumor volume in a xenograft mice model intravenously treated with HL-n without drugs after the subcutaneously inoculation of MDA-MB-453 cells was verified in vivo. Induction of apoptosis in tumor of xenograft mice treated with HL-n was observed in micrographs on the basis of TUNEL method. It was noteworthy that the therapeutic effects of HL-n along with apoptosis were obtained for xenograft mice model of human breast tumor in vivo.