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目的 研究长循环免疫脂质体 (immunoliposomes,IML)的制备方法 ,体外靶细胞杀伤活性和在小鼠体内的组织分布。方法 合成和纯化了 1个带末端羧基的磷脂酰乙醇胺 (PE)的聚乙二醇衍生物 (DPPE PEG30 0 0 COOH) ,掺入脂质体中制成长循环脂质体 ;通过羧基活泼酯化 ,将膀胱癌单克隆抗体BDI 1或小鼠IgG共价连接到该脂质体表面制成免疫脂质体 ,体外肿瘤细胞杀伤实验检测载阿霉素免疫脂质体 (ADM BDI 1 IML)特异杀伤靶细胞的能力。用同位素氚示踪法测量免疫脂质体在小鼠的组织分布。结果 抗体在脂质体上的结合率可达 30 %。体外肿瘤细胞杀伤实验证明载阿霉素免疫脂质体有选择性杀伤靶细胞人膀胱癌细胞EJ的能力。和普通脂质体相比 ,免疫脂质体在血中的滞留时间明显延长 ,并减少了在肝、脾的聚集。结论 长循环免疫脂质体在血中有较长的滞留时间 ,在体外有特异寻靶活性 ,载阿霉素免疫脂质体有选择性杀伤靶细胞的活性 ,这些性质为其在体内主动寻靶和选择性杀伤靶肿瘤细胞提供了必要条件
Objective To study the preparation of long circulating immunoliposomes (IML), target cell killing activity in vitro and tissue distribution in mice. Methods A polyethylene glycol derivative (DPPE PEG30 0 0 COOH) with terminal carboxyl groups of phosphatidylethanolamine (PE) was synthesized and purified and incorporated into liposomes to form long circulating liposomes. , The bladder cancer monoclonal antibody BDI 1 or mouse IgG covalently linked to the surface of the liposome liposomes made in vitro tumor cell killing experiments detect doxorubicin immunoliposome (ADM BDI 1 IML) specific The ability to kill target cells. Tissue distribution of immunoliposomes in mice was measured by isotope tritium tracing. Results The binding rate of antibodies on liposomes can reach 30%. In vitro tumor cell killing experiments demonstrated that doxorubicin-immunized liposomes selectively kill target cells in human bladder cancer cells EJ. Compared with ordinary liposomes, immunoliposomes in the blood retention time was significantly extended, and reduce the aggregation in the liver and spleen. Conclusion Long circulating immunoliposomes have longer residence time in the blood and specific target activity in vitro. Adriamycin-loaded immunoliposomes selectively kill the target cells. These properties are active in vivo Targets and selective killing of target tumor cells provide the necessary conditions