乳糖脂修饰的阿霉素脂质体体外杀伤肝癌细胞的实验研究

Experimental study on antitumor activity of neo-lactolipid modified adriamycin liposome on SMMC-7721

在ＮａＢＨ４还原作用下制备乳糖酰磷脂酸乙醇胺（Ｌａｃ－ＰＥ），反应４００ｈ测定仍联率为４８．６％，硅酸柱纯化得纯品。用该脂质修饰阿霉素脂质体表面，观察体外对人肝癌细胞系ＳＭＭＣ－７７２１的杀伤作用。方法乳糖和磷脂酰乙醇胺经化学反应制备Ｌａｃ－ＰＥ，用１０％摩尔的糖脂整合到超声法制备的小单层阿霉素脂质体脂膜上进行体外杀瘤研究，ＮＴＴ法检测杀瘤活性。结果４８小时细胞毒试验糖脂阿霉素脂质体对人肝癌细胞系ＳＭＭＣ－７７２１的杀伤作用优于无糖脂阿霉素脂质体（Ｐ＜０．０１），而对非靶细胞（Ｂ１６黑色素瘤细胞）的杀伤作用优于无糖脂阿霉素脂质体两者相近。０．５ｈ预处理实验表明：缩短药物与细胞接触时间后，糖脂阿霉素脂质体仍保持较强的杀伤肝癌细胞作用。结论乳糖脂阿霉素脂质体的杀伤作用来自乳糖中的半乳糖基配体的特异性介导和人肝癌细胞上肝半乳糖受体的识别内吞作用。

Aim Experimental study on antitumor activity of neolactolipi d- modifi ed adri amyc in (ADM ) liposomes onSMMC-7721 in vitro was carried out in older to observe the targeting effect of lacto-ligang to hepatic galactose receptors onSMMC-7721 cell line. Method Lacto- Phosphatidylethanoldrine (Lac- PE ) was synthesized by a series Of reaction from lac tose and Phosphatidylethamine ne, and incorpothed into Small Unilamellar Ves teles (SUV ) whi oh was preped by sonicationat the ratio of L-a-PC: CHOL: L-a-PE(7: 2: 1 molar ratio) with or without 10 mol % be-PE. Cytotoxicity assay on SMMC-7721 in vitro was Performed with Mrs methods and corn^d with free ADM or control liposome. Results Results of 48h cytotoxicity assay with MTT method showed that speCific cytotoxicity of lactolipid groups tO SMMC-7721 was 24 fold more effectivethan the conttrol group, but with very similax cytotoxicity to non-act B16 melanoma cells. 0. 5h pretreatment assay demonstratedthat cytototicity of free ADM on SMMC-7721 decreased relnarkably (IC50 = 80.9μmol/L), but lactolipid ADM liposomes remained higher (IC50 = 4 .27μmol/L) than control group IC50 > 100μmol/L) after reducing the contact time between drugs andcells. Conclusions Results indicated that higher cytotoxicity of lactolipid-mwhfied ADM liposome is due to receptor-mediatedendocytosis of hepatic galactose receptor on SMMC-7721, this method has high potency, speCificity, minimal dosage etc.