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.
Division of Applied Life Science, Graduate School of Engineering, Sojo University, 4-22-1 Ikeda, Kumamoto, Japan.
Shinya
S
Shimoda
Hideaki
H
Ichihara
Yoko
Y
Matsumoto
Ryuichi
R
Ueoka
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D006801:Humans; D008081:Liposomes / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D008081:Liposomes