Wan Xiuyan, Ge Yingli, Zhu Wanqi, Zhang Jie, Pan Wei, Li Na, Tang Bo
College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
Laoshan Laboratory, Qingdao, 266237, P. R. China.
Biomater Sci. 2025 May 13;13(10):2704-2712. doi: 10.1039/d5bm00363f.
Small interfering RNA (siRNA) is a potent method for silencing survivin mRNA within cells, offering a promising option for treating hepatocellular carcinoma (HCC) since survivin is specifically overexpressed in HCC cells. However, the clinical use of gene therapy with siRNA is limited by factors such as rapid enzyme degradation, low cell uptake, and non-specific distribution in the body. In this study, we investigate the use of a specially selected metal-organic framework (MOF) to encapsulate siRNA, with the aim of silencing survivin mRNA in HCC cells and reducing the survivin protein level. The MOF was functionalized with triantennary -acetylgalactosamine (GalNAc), which has high affinity for asialoglycoprotein receptors that are overexpressed in HCC cells. Both and experiments showed that the GalNAc-decorated MOF specifically accumulated in HCC tumor tissue and was effectively endocytosed by HCC cells. The protective properties of the MOF increased the stability of siRNA and allowed for significant downregulation of survivin expression in HCC tumors, contributing to tumor inhibition through the suppression of cell proliferation and the induction of apoptosis. These findings highlight the potential of MOF-based siRNA delivery systems for targeted cancer therapy.
小干扰RNA（siRNA）是一种在细胞内使生存素mRNA沉默的有效方法，由于生存素在肝癌（HCC）细胞中特异性过表达，为治疗肝癌提供了一个有前景的选择。然而，siRNA基因治疗的临床应用受到诸如快速酶降解、低细胞摄取和在体内非特异性分布等因素的限制。在本研究中，我们研究了使用一种特别选择的金属有机框架（MOF）来包裹siRNA，目的是使HCC细胞中的生存素mRNA沉默并降低生存素蛋白水平。该MOF用三触角 - 乙酰半乳糖胺（GalNAc）进行功能化，GalNAc对在HCC细胞中过表达的去唾液酸糖蛋白受体具有高亲和力。体内和体外实验均表明，GalNAc修饰的MOF特异性积聚在HCC肿瘤组织中，并被HCC细胞有效内吞。MOF的保护特性提高了siRNA的稳定性，并使HCC肿瘤中生存素表达显著下调，通过抑制细胞增殖和诱导凋亡促进肿瘤抑制。这些发现突出了基于MOF的siRNA递送系统在靶向癌症治疗中的潜力。
