叶酸靶向负载索拉非尼的磁性纳米胶束的制备及其在体外对人肝癌细胞的靶向治疗作用  

In vitro targeted therapy on human hepatic carcinoma cells using folate-functionilazed sorafenibloaded magnetic polymeric micelles

作　　者：马靖[1] 张磊[1] 巩发明[3] 张芳[2] 张培东[1] 

机构地区：[1]中山大学孙逸仙纪念医院肝胆胰外科,广州510120 [2]中山大学孙逸仙纪念医院放射科,广州510120 [3]中山大学化学与化学工程学院

出　　处：《中华实验外科杂志》2013年第3期490-492,共3页Chinese Journal of Experimental Surgery

基　　金：广东省自然科学基金资助项目（$2012010009741）;北京市希思科I临床肿瘤学研究基金会资助项目（Y-B2012-001）

摘　　要：目的探讨叶酸修饰的负载索拉非尼及超顺磁性氧化铁（SPIO）的磁性纳米胶束的制备及其在体外对人肝癌细胞HepG2的靶向性、增殖抑制及促凋亡作用。方法制备由叶酸修饰及无叶酸修饰的负载索拉非尼的磁性纳米胶束，将不同浓度（10．0000、5．0000、2．5000、1．2500、0．6250、0．3125μmol／L）的纳米胶束分别与人肝癌细胞HepG2共孵育ih，以普鲁士蓝染色观察其靶向性，以噻唑蓝（MTT）法测定HepG2的增殖，以流式细胞仪检测细胞凋亡。结果叶酸靶向纳米胶束与HepG2细胞共孵育后行普鲁士蓝染色显示细胞内存在大量铁，非叶酸靶向纳米胶束及体外竞争抑制实验普鲁士蓝染色显示细胞内铁浓度极低；MTT法显示叶酸靶向药物组对HepG2细胞的总平均抑制率为38．13％，非叶酸靶向药物组为22．54％，两者差异有统计学意义（P〈0．05）；流式细胞术显示叶酸靶向药物组的平均细胞凋亡率为17．01％，非叶酸靶向药物组为11．04％，而对照组为7．89％，叶酸靶向药物组的细胞凋亡率较非叶酸靶向药物组升高更为明显，差异有统计学意义（P〈0．05）。结论叶酸修饰的负载索拉非尼的磁性纳米胶束在体外对人肝癌细胞HepG2具有良好的靶向性、增殖抑制及促凋亡作用。Objective To evaluate the tumor targeting characteristic and the inhibitory effect to human hepatic carcinoma cells （ HepG2 cells ） of the folate-superparamagnetic iron oxide （ SPIO ） -sor- afenib-micelles （ targeted ~nicelles） by in vitro studies. Methods First of all, the synthesis of targeted mi- celles was completed and the folate-free sorafenib-mieelles （non-targeted mieelles ） were used as control. Cell suspensions were incubated with the polymeri micelles with different sorafenib concentrations （ 10. 0000, 5.0000, 2. 5000, 1. 2500, 0. 6250, 0. 3125 μmol/L） for 1 h. Prussian blue staining was performed to show intracellular irons. The inhibitory effect on HepG2 cells proliferation in vitro was assessed by methyl thiazolyl tetrazolium （MTY） assay and the apoptotie rate of the treated cells were detected by flow cytometry. Results Prussian blue staining showed much more intracellular iron in cells incubated with targeted micelles than non- targeted micelles. MTI＂ assay showed that the average inhibitive ratio in the folate group and the folate-free group were 38. 13% and 22. 54% （P 〈0. 05）. The mean apoptotic rate of treated cells in the folate group, the folate-free group and the control group were 17.01%, 11.04% and 7.89% , and the apoptotic rate in the folate group was higher than the folate-free group （ P 〈 0. 05 ）. Conclusion Targeted micelles have better targeting tropism to the hepatic carcinoma ceils in vitro than non-targeted micelles and show the effect in in- hibiting the proliferation and inducing apopotisis of HepG2 cells in vitro.

关 键 词：叶酸 索拉非尼 纳米胶束 靶向治疗 

分 类 号：R9[医药卫生—药学]