M-MSNs作为基因载体应用于卵巢癌的可行性研究The feasibility study of M-MSNs used as gene carrier in ovarian cancer
王欣然;陈一杰;王云飞;刘婷;古宏晨;狄文;
摘要(Abstract):
目的:研究磁性介孔二氧化硅纳米粒(M-MSN)作为小干扰RNA(siRNA)载体应用于卵巢癌的可行性,并初步探讨其作用机制。方法:CCK-8试剂盒检测M-MSN对SKOV3的细胞毒作用,共聚焦显微镜下观察SKOV3细胞对M-MSN的摄取以及M-MSN的溶酶体逃逸并释放siRNA的过程。磁共振成像(MRI)观察纳米粒对原位SKOV3肿瘤的靶向性。结果:与M-MSN共培养24h后,SKOV3细胞的生长未受影响。与细胞共培养后,M-MSN颗粒可被SKOV3细胞大量摄取,保护siRNA免被溶酶体内的水解酶溶解,并在细胞内与功能完整的siRNA成功分离。SKOV3原位荷瘤体内实验发现,静脉注射MMSN纳米粒后,M-MSN可成功到达卵巢原位,并在肿瘤组织中积聚。结论:M-MSN是siRNA的良好载体,具有很好的生物安全性,可成功保护siRNA免被破坏,并释放到卵巢癌细胞质内。同时由于M-MSN颗粒的T2负增强造影剂作用,可同时实现肿瘤部位显像,其作为新型诊疗一体纳米颗粒具有极大的应用价值。
关键词(KeyWords): 卵巢癌;小干扰RNA;介孔无机颗粒;磁共振成像
基金项目(Foundation): 卵巢癌物理治疗临床转化研究示范基地(No:11DZ2211002);; 上海市科委纳米专项基金(No:11nm0503000);; 上海市高等学校科学技术发展基金(No:zzjdyx13060)
作者(Authors): 王欣然;陈一杰;王云飞;刘婷;古宏晨;狄文;
DOI: 10.13283/j.cnki.xdfckjz.2014.07.006
参考文献(References):
- [1]Wang Zh,Rao DD,Senzer N,et al.RNA interference and cancer therapy[J].Pharm Res,2011,28(12):2983-2995
- [2]Fathabadi EG,Shelling AN,Al-Kassas R.Nanocarrier systems for delivery of siRNA to ovarian cancer tissues[J].Expert Opin Drug Deliv,2012,9(7):743-754
- [3]Tang F,Li L,Chen D.Mesoporous silica nanoparticles:synthesis,biocompatibility and drug delivery[J].Adv Mater,2012,24(12):1504-1534
- [4]Vaughan S,Coward JI,Bast RC,et al.Rethinking ovarian cancer:Recommendations for improving outcomes[J].Nat Rev Cancer,2011,11(10):719-725
- [5]Disaia PJ,Bloss JD.Treatment of ovarian cancer:new strategies[J].Gynecol Oncol,2003,90(2 Pt 2):S24-32
- [6]Tanaka K,Kanazawa T,Ogaw T,et al.Disulfide crosslinked stearoyl carrier peptides containing arginine and histidine enhance siRNA uptake and gene silencing[J].Int J Pharm,2010,398(1-2):219-224
- [7]Burnett JC,Rossi JJ,Tiemann K.Current progress of siRNA/shRNA therapeutics in clinical trials[J].Biotechnol,2011,6(9):1130-1146
- [8]Carlee EA,Eric CC,Genevieve KP,et al.The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers[J].Nat Mater,2011,10(5):389-397
- [9]Halas NJ.Nanoscience under Glass:the Versatile Chemistry of Silica Nanostructures[J].ACS Nano,2008,2(2):179-183
- [10]Liu Q,Zhang J,Xia W,et al.Towards magnetic-enhanced celluar uptake,MRI and chemotherapeutics delivery by magnetic mesoporous silica nanoparticles[J].Nanosic Nanotechnol,2012,10(12):7709-7715