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磁性阳离子直链淀粉纳米颗粒用于体外递送生存素小干扰RNA进行肝细胞癌基因治疗

Magnetic Cationic Amylose Nanoparticles Used to Deliver Survivin-Small Interfering RNA for Gene Therapy of Hepatocellular Carcinoma In Vitro.

作者信息

Wu Zhuo, Xu Xiao-Lin, Zhang Jun-Zhao, Mao Xu-Hong, Xie Ming-Wei, Cheng Zi-Liang, Lu Lie-Jing, Duan Xiao-Hui, Zhang Li-Ming, Shen Jun

机构信息

Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.

Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.

出版信息

Nanomaterials (Basel). 2017 May 11;7(5):110. doi: 10.3390/nano7050110.

Abstract

Amylose is a promising nanocarrier for gene delivery in terms of its good biocompatibility and high transfection efficiency. Small interfering RNA against survivin (survivin-siRNA) can cause tumor apoptosis by silencing a hepatocellular carcinoma (HCC)-specific gene at the messenger RNA level. In this study, we developed a new class of folate-functionalized, superparamagnetic iron oxide (SPIO)-loaded cationic amylose nanoparticles to deliver survivin-siRNA to HCC cells. The cellular uptake of nanocomplexes, cytotoxicity, cell apoptosis, and gene suppression mediated by siRNA-complexed nanoparticles were tested. The results demonstrated that folate-functionalized, SPIO-loaded cationic amylose nanoparticles can mediate a specific and safe cellular uptake of survivin-siRNA with high transfection efficiency, resulting in a robust survivin gene downregulation in HCC cells. The biocompatible complex of cationic amylose could be used as an efficient, rapid, and safe gene delivery vector. Upon SPIO loading, it holds a great promise as a theranostic carrier for gene therapy of HCC.

摘要

就其良好的生物相容性和高转染效率而言,直链淀粉是一种很有前景的基因递送纳米载体。针对生存素的小干扰RNA(生存素-siRNA)可通过在信使核糖核酸水平沉默一种肝细胞癌(HCC)特异性基因来诱导肿瘤细胞凋亡。在本研究中,我们开发了一类新型的叶酸功能化、负载超顺磁性氧化铁(SPIO)的阳离子直链淀粉纳米颗粒,用于将生存素-siRNA递送至肝癌细胞。测试了纳米复合物的细胞摄取、细胞毒性、细胞凋亡以及由与siRNA复合的纳米颗粒介导的基因抑制作用。结果表明,叶酸功能化、负载SPIO的阳离子直链淀粉纳米颗粒能够以高转染效率介导生存素-siRNA的特异性和安全的细胞摄取,从而导致肝癌细胞中生存素基因的显著下调。阳离子直链淀粉的生物相容性复合物可作为一种高效、快速且安全的基因递送载体。负载SPIO后,它作为肝癌基因治疗的诊疗载体具有巨大的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be5/5449991/05d6d6b98f5c/nanomaterials-07-00110-g001.jpg

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