多烯紫杉醇主动靶向脂质体对S180肉瘤细胞小鼠移植瘤生长的影响  

Inhibitory Effect of Active Targeting Docetaxel-loaded Liposomes on S180 Cell Transplanted Tumor in Mice

作　　者：李翔[1,2] 罗晓健[1] 王东凯[2] 潘卫三[2] 张婧[1] 

机构地区：[1]江西中医药大学中药固体制荆制造技术国家工程研究中心,南昌330006 [2]沈阳药科大学药学院,沈阳110016

出　　处：《中国实验方剂学杂志》2015年第12期77-80,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81202927);江西省教育厅青年基金项目(GJJ12536);江西省科技支撑计划项目(20123BBG70181);江西省青年科学基金项目(20132BAB215022,20122BAB215018);江西省卫生厅中医药科研计划项目(2012A157)

摘　　要：目的:研究叶酸受体多烯紫杉醇主动靶向脂质体(FA-PDCT-L)对S180肉瘤细胞小鼠移植瘤的抑制作用及体内毒性。方法:利用自制两亲性嵌段共聚物叶酸-聚乙二醇-聚胆固醇氰基丙烯酸脂(FA-PEG-PCHL)修饰FA-PDCT-L,采用激光共聚焦显微镜检测脂质体与MCF-7细胞的结合机制;建立S180肉瘤细胞小鼠皮下移植瘤动物模型,随机分为DCT注射液(DCT-I)、未修饰DCT脂质体(DCT-L)和FA-PDCT-L和模型组(生理盐水),按10 mg·kg-1·d-1尾静脉注射给药,观察小鼠移植瘤生长变化并计算抑瘤率;采用TUNEL法测定细胞凋亡;观察各组动物肝功能及骨髓抑制血液生化指标。结果:FA-PDCTL与MCF-7细胞的结合量明显高于其他试验组。与模型相比,DCT-I,DCT-L和FA-PDCT-L组小鼠瘤体积均减少,其中FAPDCT-L的作用最为显著,抑瘤率79.03%,凋亡指数(45.7±3.4)%。FA-PDCT-L组动物的肝功能及骨髓抑制生化指标均与空白组无显著差异。结论:FA-PDCT-L通过FA-PEG-PCHL介导的细胞内化使脂质体进入细胞,显示出了比市售DCT-I更好的抗肿瘤疗效和更低的毒性。Objective： To study inhibitory effect of folate receptor active targeting docetaxel-loaded liposomes （FA-PDCT-L） on S180 cell transplanted tumor and its in vivo toxicity in mice. Method： A self synthesized amphiphilic copolymer, folate-poly （ PEG-cyanoacrylate-co-cholesteryl cyanoacrylate ） （ FA-PEG- PCHL） was used as liposomal modifying material to form FA-PDCT-L. Confocal laser scanning microscopy was adopted to detect affinity between liposomes and MCF-7 cells. Subcutaneous transplanted model of S180 sarcoma was made. Tumor mice were randomized into 4 groups, such as docetaxel （DCT） injection （DCT-I） , unmodified DCT-loaded liposomes （DCT-L）, FA-PDCT-L and model group （saline）, dosages were 10 mg·kg^-1·d^-1 through tail vein. Tumor weight and inhibition rate of tumor were detected at the end of experiments, tumor cell apoptosis was analyzed by TUNEL. Hepatic function and hematology assay for myelosuppression were evaluated. Result：FA-PDCT-L had better affinity to cells than the other two reference preparation. Compared with model group, weight of tumor in DCT-I, DCT-L and FA-PDCT-L were decreased, especially for FA-PDCT-L, its inhibitory rates was 79.03% with apoptosis index at （45.7 ± 3.4） %. There was no significant difference of hepatic function and hematology assay between the FA-PDCT-L group and the blank group. Conclusion： FA-PDCT-L is internalized into cells by mediation of FA-PEG-PCHL with better anti-tumor activity and lower in vivo toxicity by compared with DCT-I.

关 键 词：多烯紫杉醇 主动靶向脂质体 抗肿瘤活性 毒性 香豆素6 

分 类 号：R283.6[医药卫生—中药学] R945[医药卫生—中医学]