新型靶向性表阿霉素复方脂质体的研制及其对侵袭性乳腺癌细胞的抑制效应  

Preparation of targeted epirubicin plus curcumin liposomes modified with DSPE-PEG_(2000)-raltitrexed and their inhibitory effect on invasive breast cancer

作　　者：孙梦舸 石继凤 李秀英[1] 赵曜[1] 吕万良[1] 

机构地区：[1]北京大学天然药物及仿生药物国家重点实验室药学院药剂学系,北京100191

出　　处：《中国新药杂志》2014年第19期2291-2297,共7页Chinese Journal of New Drugs

基　　金：国家自然科学基金(81373343);北京市自然科学基金重点项目(7131009);教育部创新团队基金(BMU20110263)

摘　　要：目的:构建新型靶向性载药脂质体、并考察其对侵袭性乳腺癌细胞的抑制效应。方法:以叶酸类似物雷替曲塞为靶向分子,通过与长循环磷脂材料进行化学合成,制备针对乳腺癌叶酸受体的靶向性功能材料;并将之修饰到脂质体上,以表阿霉素为抗癌药、姜黄素为抗耐药调控剂,制备靶向性表阿霉素复方脂质体;对该脂质体进行理化表征;在人源性低侵袭性乳腺癌MCF-7细胞和高侵袭性乳腺癌MDA-MB-231细胞中,考察其摄取情况和抑制效应。结果:由MALDI-TOF-MS分析证实,成功的制备了DSPE-PEG_(2000)-raltitrexed靶向材料。构建的靶向性表阿霉素复方脂质体粒径约100 nm、分散均一、呈电中性。表阿霉素包封率约为95%,姜黄素包封率约为80%。流式细胞仪测定结果显示,相对于对照制剂,靶向性表阿霉素复方脂质体在2种癌细胞中摄取率均显著提高、对癌细胞抑制效果明显增强。结论:本研究合成了一种新的靶向性功能材料DSPE-PEG_(2000)-raltitrexed,构建的新型靶向性表阿霉素复方脂质体可以明显抑制乳腺癌增殖,表现出抗高侵袭性乳腺癌的潜能。Objective ： To develop a new kind of targeted epirubicin plus curcumin liposomes and to determine their inhibitory effect on the invasive breast cancer. Methods： Raltitrexed was used as a targeting molecule and conjugated with DSPE-PEG2000-NH2 for obtaining a targeting functional material. To prepare targeted epirubicin plus curcumin liposomes, the targeting functional material was modified onto the liposomal vesicle, and epirubicin was loaded into the liposomes as the anticancer drug by incorporating curcumin as the anti-resistant regulating agent. The encapsulation efficiency, particle size, and zeta potential values of the constructed liposomes were charaeterized, and their cellular uptakes and inhibitory effects were performed on the less invasive human breast cancer MCF-7 cells and the high invasive human breast cancer MDA-MB-231 cells. Results： The analysis by MALDI- TOF-MS demonstrated that the targeting material DSPE-PEG2000-rahitrexed was successfully synthesized. The targe- ted epirubicin plus curcumin liposomes were uniformly dispersed and neutrally charged. Their average particle size was approximately 100 nm. The encapsulation efficiencies of epirubicin and curcumin were about 95% and 80% ,respectively. Results from flow cytometric and cytotoxic studies showed that the targeted epirubicin plus curcumin liposomes had the highest cellular uptake and the highest inhibitory effect compared with non-targeted drug liposomes in the two kinds of breast cancer cells. Conclusion： A new compound DSPE-PEG2000-rahitrexed is synthesized as the folate-receptor targeting functional material. The targeted epirubicin plus curcumin liposomes demonstrate a strong potential in inhibiting both invasive and less invasive breast cancer cells.

关 键 词：雷替曲塞 靶向性表阿霉素复方脂质体 表阿霉素 姜黄素 侵袭性乳腺癌 

分 类 号：R979.1[医药卫生—药品]