Chemotherapy with Hybrid Liposomes Along with Induction of Apoptosis

混合脂质体可以通过简单地超声处理缓冲溶液中的囊泡和胶束分子的混合物来制备。通过改变脂质体的组成，可以控制脂质体的大小、膜流动性、相变温度和疏水性等物理性质，并研究了由亲水性头部基团（磷脂酰胆碱基团）相同、疏水性烷基链不同的磷脂（L-α-二月桂酰磷脂酰胆碱（C<12>_：DLPC）、L-α-二肉豆蔻酰磷脂酰胆碱（C_：DMPC）、L<14>-α-二棕榈酰磷脂酰胆碱（C_<16>：DPPC））和聚氧乙烯十二烷基醚（C_<12>（EO）_<23>）组成的杂化脂质体对人白血病（HL 60）细胞体外生长的抑制作用。由DMPC和聚氧乙烯（10）十二烷基醚（C_<12>（EO）_<10>）组成的杂化脂质体在不使用任何药物的情况下对人早幼粒细胞白血病（HL-60）细胞有明显的抑制作用，通过荧光显微镜和流式细胞仪分析，证实了杂化脂质体在HL-60细胞中的诱导凋亡作用。阐明了脂质体诱导细胞凋亡的途径。细胞凋亡信号首先通过线粒体、caspase-9和caspase-3，再通过Fas、caspase-8和caspase-3到达细胞核。DMPC/C_（EO）_2杂化脂质体本身能沿着诱导人肿瘤细胞凋亡，并对肿瘤细胞生长有明显的抑制作用，本文研究了DMPC/C_<12>（EO）_2<23>杂化脂质体对小鼠肿瘤的治疗作用。DMPC/C_（EO）_2复合脂质体可使小鼠存活率提高150%<12>，且<23>无任何毒副作用。

Hybrid liposomes can be prepared by simply ultrasonicating a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of these liposomes, such as size, membrane fluidity, phase transition temperature, and hydrophobicity can be controlled by changing the composition.The inhibitory effects of hybrid liposomes composed of phospholipids having the same hydrophilic head group (phosphatidylcholine group) and different hydrophobic alkyl chains (L-α-dilauroylphosphatidylcholine (C_<12>: DLPC), L-α-dimyristoylphosphatidylcholine (C_<14>: DMPC), L-α-dipal-mitoylphosphatidylcholine (C_<16>:DPPC)) and polyoxyethylene-dodecyl ether (C_<12>(EO)_<23>) on the growth of human leukemia (HL60) cells in vitro were examined. Hybrid liposomes composed of DMPC and polyoxyethylene (10) dodecyl ether (C_<12>(EO)_<10>) were found to inhibit the growth of human promyelocytic leukemia (HL-60) cells without using any drugs.Induction of apoptosis by hybrid liposomes in HL-60 cells was verified on the basis of fluorescence microscopy and flow cytometry analysis, after fusion and accumulation of hybrid liposomes which was revealed on the basis of microphysiometer. We elucidated the pathways of apoptosis induced by the hybrid liposomes. That is, hybrid liposomes fused and accumulated in tumor cell membranes, and the apoptosis signal first passed through mitochondria, caspase-9 and caspase-3, second through Fas, caspase-8, caspase-3 and then reached the nucleus. Hybrid liposomes themselves can induce apoptosis in human tumor cells along with high inhibitory effects on the growth of tumor cells.We examined therapeutic effects of DMPC/C_<12>(EO)_<23> hybrid liposomes on mice model of carcinoma in vitro. The prolonged survival ratio of 150% was obtained in the treated with hybrid liposomes of DMPC/C_<12>(EO)_<23> without any side effects.