Hanafi-Bojd Mohammad Yahya, Jaafari Mahmoud Reza, Ramezanian Navid, Abnous Khalil, Malaekeh-Nikouei Bizhan
School of Pharmacy, Mashhad University of Medical Sciences, P.O. Box 91775-1365, Mashhad, Iran.
Curr Drug Deliv. 2016;13(7):1176-1182. doi: 10.2174/1567201813666151231094056.
Development of drug resistance to anticancer drugs is an important challenge for cancer treatment. Recent studies focus on co-delivery of anticancer drugs and siRNA to overcome this challenge. Mesoporous silica nanoparticles (MSNs) are one of the promising nanoparticles that enable the delivery of drugs and siRNA simultaneously. MSNs coated with copolymer capable of co-delivery of drug and siRNA were prepared and characterized. In the present study, MSNs functionalized with polyethylenimine-polyethylene glycol (PEI-PEG) copolymer were prepared. MSNs were characterized using dynamic light scattering (DLS), Transmission Electron Microscopy (TEM) and elemental analysis. Nanoparticles were loaded with epirubicin hydrochloride (EPI) and anti B-cell lymphoma 2 (BCL-2) siRNA. The in vitro cytotoxicity and in vivo efficacy of different formulations were evaluated. Mean size of MSNs ranged from 98 to 247 nm. EPI release from MSNs was pH-dependent. MSNs loaded with EPI and siRNA showed better in vitro cytotoxicity with 1 μg/mL EPI and 50-400 ng/mL siRNA, besides MSNs loaded with 9 mg/kg EPI and 1.2 mg/kg siRNA resulted in improved in vivo effects compared to EPI or MSNs containing EPI or siRNA alone. The results of in vitro and in vivo studies indicated the synergistic effect of EPI and anti BCL-2 siRNA. This formulation could be a promising nanoparticle for codelivery of drug and siRNA in cancer cells.
抗癌药物耐药性的产生是癌症治疗面临的一项重大挑战。近期研究聚焦于同时递送抗癌药物和小干扰RNA（siRNA）以克服这一挑战。介孔二氧化硅纳米颗粒（MSNs）是有望实现药物和siRNA同时递送的纳米颗粒之一。制备并表征了涂覆有能够同时递送药物和siRNA的共聚物的MSNs。在本研究中，制备了用聚乙烯亚胺-聚乙二醇（PEI-PEG）共聚物功能化的MSNs。使用动态光散射（DLS）、透射电子显微镜（TEM）和元素分析对MSNs进行了表征。纳米颗粒负载了盐酸表柔比星（EPI）和抗B细胞淋巴瘤2（BCL-2）siRNA。评估了不同制剂的体外细胞毒性和体内疗效。MSNs的平均粒径范围为98至247nm。EPI从MSNs中的释放呈pH依赖性。负载EPI和siRNA的MSNs在1μg/mL EPI和50 - 400ng/mL siRNA时表现出更好的体外细胞毒性，此外，负载9mg/kg EPI和1.2mg/kg siRNA的MSNs与单独的EPI或含有EPI或siRNA的MSNs相比，体内效果有所改善。体外和体内研究结果表明了EPI和抗BCL-2 siRNA的协同作用。这种制剂可能是一种在癌细胞中同时递送药物和siRNA的有前景的纳米颗粒。
