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用新型多肽修饰纳米颗粒靶向递送HES5-siRNA用于肝细胞癌治疗

Targeted delivery of HES5-siRNA with novel polypeptide-modified nanoparticles for hepatocellular carcinoma therapy.

作者信息

Xia Yu, Wang Changbing, Xu Tiantian, Li Yinghua, Guo Min, Lin Zhengfang, Zhao Mingqi, Zhu Bing

机构信息

Guangzhou Women and children's Medical center No 318 Renminzhong road Yuexiu District Guangzhou Guangdong 510120 P. R. China

出版信息

RSC Adv. 2018 Jan 9;8(4):1917-1926. doi: 10.1039/c7ra12461a. eCollection 2018 Jan 5.

DOI:10.1039/c7ra12461a
PMID:35542585
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9077277/
Abstract

For actively targeted delivery of small interfering RNA (siRNA) to solid tumors, we fabricated functionalized selenium nanoparticles (SeNPs) decorated with the polypeptide RGDfC. Herein, RGDfC was used as tumor-targeted moiety and installed onto the surface of SeNPs to enhance the cellular uptake. RGDfC-SeNPs@siRNA were internalized into the HepG2 cell mainly through clathrin-mediated endocytosis. The active efficacy of the RGDfC-SeNPs@siRNA was confirmed gene silencing assay, MTT assay and flow cytometry analysis. Owing to the tumor-targeting effect of RGDfC, RGDfC-SeNPs@siRNA achieved an obvious improvement in gene silencing ability, which led to significant growth inhibition of HepG2 cells. Furthermore, treatment with RGDfC-SeNPs@siRNA resulted in greater antitumor efficacy than lipofectamine 2000@siRNA and . In addition, the RGDfC-SeNPs@siRNA was almost non-toxic to the key organs of mice. In sum, these findings provide an alternative therapeutic route for targeted cancer treatments.

摘要

为了将小干扰RNA（siRNA）主动靶向递送至实体瘤，我们制备了用多肽RGDfC修饰的功能化硒纳米颗粒（SeNPs）。在此，RGDfC用作肿瘤靶向部分，并安装在SeNPs表面以增强细胞摄取。RGDfC-SeNPs@siRNA主要通过网格蛋白介导的内吞作用内化到HepG2细胞中。通过基因沉默实验、MTT实验和流式细胞术分析证实了RGDfC-SeNPs@siRNA的活性功效。由于RGDfC的肿瘤靶向作用，RGDfC-SeNPs@siRNA在基因沉默能力方面有明显提高，这导致HepG2细胞的生长受到显著抑制。此外，用RGDfC-SeNPs@siRNA处理比用脂质体2000@siRNA处理具有更高的抗肿瘤功效。此外，RGDfC-SeNPs@siRNA对小鼠的关键器官几乎无毒。总之，这些发现为靶向癌症治疗提供了一条替代治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/f8d6d1e6825b/c7ra12461a-f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/8dfd2cf15a83/c7ra12461a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/1b5dbc19e182/c7ra12461a-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/6a4a62f36e1f/c7ra12461a-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/f8d6d1e6825b/c7ra12461a-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/63af5e589299/c7ra12461a-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/56cbe1eb85cb/c7ra12461a-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/fede2ed3b50b/c7ra12461a-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/8dfd2cf15a83/c7ra12461a-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/1b5dbc19e182/c7ra12461a-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e96/9077277/6a4a62f36e1f/c7ra12461a-f6.jpg
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