Chen Si, Zhang Shuang, Wang Yifan, Yang Xin, Yang Hong, Cui Chunying
School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.
Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing 10069, China.
Asian J Pharm Sci. 2021 Sep;16(5):598-611. doi: 10.1016/j.ajps.2021.04.002. Epub 2021 Jul 22.
Graphene oxide (GO) has emerged as a potential drug delivery vector. For siRNA delivery, GO should be modified to endow it with gene delivery ability and targeting effect. However, the cationic materials used previously usually had greater toxicity. In this study, GO was modified with a non-toxicity cationic material (chitosan) and a tumor specific monoclonal antibody (anti-EpCAM) for the delivery of survivin-siRNA (GCE/siRNA). And the vector (GCE) prepared was proved with excellent biosafety and tumor targeting effect. The GCE exhibited superior performance in loading siRNA, maintained stability in different solutions and showed excellent protection effect for survivin-siRNA . The gene silencing results showed that the mRNA level and protein level were down-regulated by 48.24% ± 2.50% and 44.12% ± 3.03%, respectively, which was equal with positive control ( > 0.05). It was also demonstrated that GCE/siRNA had a strong antitumor effect , which was attributed to the efficient antiproliferation, and migration and invasion inhibition effect of GCE/siRNA. The results indicated that GCE could accumulate siRNA in tumor tissues. The tumor inhibition rate of GCE/siRNA 54.74% ± 5.51% was significantly higher than control 4.87% ± 8.49%. Moreover, GCE/siRNA showed no toxicity for blood and main organs, suggesting that it is a biosafety carrier for gene delivery. Taken together, this study provides a novel design strategy for gene delivery system and siRNA formulation.
氧化石墨烯（GO）已成为一种潜在的药物递送载体。对于小干扰RNA（siRNA）递送而言，GO需要进行修饰以赋予其基因递送能力和靶向作用。然而，此前使用的阳离子材料通常具有较大的毒性。在本研究中，采用无毒阳离子材料（壳聚糖）和肿瘤特异性单克隆抗体（抗上皮细胞黏附分子，anti-EpCAM）对GO进行修饰，用于递送生存素小干扰RNA（GCE/siRNA）。所制备的载体（GCE）具有优异的生物安全性和肿瘤靶向作用。GCE在装载siRNA方面表现出卓越性能，在不同溶液中保持稳定，并且对生存素小干扰RNA显示出优异的保护作用。基因沉默结果表明，mRNA水平和蛋白质水平分别下调了48.24%±2.50%和44.12%±3.03%，与阳性对照相当（>0.05）。还证明了GCE/siRNA具有强大的抗肿瘤作用，这归因于GCE/siRNA有效的抗增殖以及迁移和侵袭抑制作用。结果表明，GCE能够使siRNA在肿瘤组织中蓄积。GCE/siRNA的肿瘤抑制率为54.74%±5.51%，显著高于对照组的4.87%±8.49%。此外，GCE/siRNA对血液和主要器官无毒性，表明它是一种用于基因递送的生物安全载体。综上所述，本研究为基因递送系统和siRNA制剂提供了一种新颖的设计策略。
