Functionalized graphene oxide for anti-VEGF siRNA delivery: preparation, characterization and evaluation in vitro and in vivo
Functionalized graphene oxide for anti-VEGF siRNA delivery: preparation, characterization and evaluation in vitro and in vivo
复制标题
用于抗 VEGF siRNA 递送的功能化氧化石墨烯：体外和体内的制备、表征和评估
DOI：
10.1039/c7ra00810d
复制
发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Xu Ge
中科院分区：
文献类型：
--
作者：
lulu Ren;Yifan Zhang;Chunying Cui;Yanzhao Bi;Xu Ge
RNA干扰（RNA interference, RNAi）治疗是一种很有前途和有效的癌症基因治疗方法。小干扰RNA （Small interference RNA, siRNA）在RNAi过程中起着不可或缺的作用，导致基因沉默。然而，裸siRNA很难穿过细胞膜，并且很容易被酶解失活。为了克服这些缺点，siRNA的传递需要一种理想的载体。本研究制备并表征了一种活性靶向肿瘤的氧化石墨烯载体GO - pll - sdgr（聚l -赖氨酸和精氨酸-甘氨酸- asp -丝氨酸功能化氧化石墨烯）。琼脂糖凝胶阻滞实验结果表明，10 μg的GO-PLL-SDGR可负载1 μg的VEGF-siRNA。我们发现GO-PLL-SDGR /VEGF-siRNA的VEGF-siRNA释放缓慢且持续。采用RT-qPCR、ELISA和S180荷瘤小鼠模型研究了GO-PLL-SDGR /VEGF-siRNA的体外和体内基因沉默效率和肿瘤生长抑制活性。RT-qPCR和ELISA检测结果显示，体外培养大鼠VEGF- mrna和VEGF蛋白表达分别下调40.86%和51.71%。体内观察到Cy-3标记的VEGF-siRNA在肿瘤组织中聚集，GO-PLL-SDGR /VEGF-siRNA的抑瘤率为51.74%。此外，在MTT试验中，GO-PLL-SDGR表现出较低的细胞毒性。如上所述，GO-PLL-SDGR可以作为非病毒肿瘤靶向载体用于siRNA递送系统。
RNA interference (RNAi) treatment is a promising and effective method for gene therapy in cancer treatments. Small interference RNA (siRNA) plays an indispensable role in the process of RNAi, resulting in gene silencing. However, naked siRNA has difficulty in crossing the cell membrane and can easily be deactivated by enzymolysis. An ideal carrier is required for siRNA delivery to overcome these disadvantages. In this study, GO–PLL–SDGR (poly-L-lysine and Arg-Gly-Asp-Ser functionalized graphene oxide), a graphene oxide (GO)-based carrier that can actively target tumors, was prepared and characterized. Results of an agarose gel retardation assay indicated that 10 μg of GO–PLL–SDGR could load 1 μg of VEGF-siRNA. It was found that the release of VEGF-siRNA from GO–PLL–SDGR/VEGF-siRNA was slow and sustained. The efficiency of gene silencing and the tumor growth inhibitory activity of GO–PLL–SDGR/VEGF-siRNA were investigated both in vitro and in vivo by RT-qPCR, ELISA and an S180 tumor-bearing mice model. RT-qPCR and ELISA assays revealed that the expressions of VEGF-mRNA and VEGF protein were down-regulated by 40.86% and 51.71%, respectively, in vitro. In vivo, the Cy-3 labeled VEGF-siRNA was observed to assemble in tumor tissues, and the tumor inhibitory rate of GO–PLL–SDGR/VEGF-siRNA was 51.74%. What's more, GO–PLL–SDGR exhibited low cytotoxicity in the MTT assay. As all the evidence shows above, GO–PLL–SDGR could be used in siRNA delivery systems as a non-viral tumor targeting carrier.
登录
查看更多内容
影响因子：
4.6
作者：
C. Wei;Ming Chen;Feng-Er Yu
通讯作者：
C. Wei;Ming Chen;Feng-Er Yu
基于聚赖氨酸功能化石墨烯的光和化学响应纳米制剂的协同抗癌活性
影响因子：
9.5
作者：
Wu Chunhui;He Qiuming;Zhu Anni;Li Dan;Xu Min;Yang Hong;Liu Yiyao
通讯作者：
Liu Yiyao
使用可激活荧光素酶报告基因对树枝状聚合物接枝氧化石墨烯介导的抗 miR-21 递送进行成像
影响因子：
9.5
作者：
Wang Fu;Zhang Beilei;Zhou Lin;Shi Yaru;Li Zhiqiang;Xia Yuqiong;Tian Jie
通讯作者：
Tian Jie
聚乙二醇化纳米氧化石墨烯中设计的氧化还原响应性 PEG 分离机制，用于细胞内药物输送。
影响因子：
13.3
作者：
Song, Yanyan;Li, Xuequan;Li, Yongyong;Shi, Donglu
通讯作者：
Shi, Donglu
影响因子：
64.8
作者：
Stankovich, Sasha;Dikin, Dmitriy A.;Ruoff, Rodney S.
通讯作者：
Ruoff, Rodney S.