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工程化介孔硅纳米颗粒:有效癌症基因治疗的新纳米平台。

Engineered mesoporous silica nanoparticles, new insight nanoplatforms into effective cancer gene therapy.

机构信息

Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Department of Tissue Engineering & Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran.

出版信息

Int J Biol Macromol. 2023 Dec 31;253(Pt 4):127060. doi: 10.1016/j.ijbiomac.2023.127060. Epub 2023 Sep 27.

Abstract

The use of nucleic acid to control the expression of genes relevant to tumor progression is a key therapeutic approach in cancer research. Therapeutics based on nucleic acid provide novel concepts for untreatable targets. Nucleic acids as molecular medications must enter the target cell to be effective and obstacles in the systemic delivery of DNA or RNA limit their use in a clinical setting. The creation of nucleic acid delivery systems based on nanoparticles in order to circumvent biological constraints is advancing quickly. The ease of synthesis and surface modification, biocompatibility, biodegradability, cost-effectiveness and high loading capability of nucleic acids have prompted the use of mesoporous silica nanoparticles (MSNs) in gene therapy. The unique surface features of MSNs facilitate their design and decoration for high loading of nucleic acids, immune system evasion, cancer cell targeting, controlled cargo release, and endosomal escape. Reports have demonstrated successful therapeutic outcomes with the administration of a variety of engineered MSNs capable of delivering genes to tumor sites in laboratory animals. This comprehensive review of studies about siRNA, miRNA, shRNA, lncRNA and CRISPR/Cas9 delivery by MSNs reveals engineered MSNs as a safe and efficient system for gene transfer to cancer cells and cancer mouse models.

摘要

利用核酸来控制与肿瘤进展相关的基因表达是癌症研究中的一个关键治疗方法。基于核酸的治疗为不可治疗的靶点提供了新的概念。核酸作为分子药物,必须进入靶细胞才能发挥作用,而 DNA 或 RNA 的系统递送中的障碍限制了它们在临床环境中的应用。为了克服生物学限制而创建基于纳米粒子的核酸递药系统正在迅速发展。核酸易于合成和表面修饰、生物相容性、可生物降解性、成本效益和高载药能力促使人们将介孔硅纳米粒子(MSNs)用于基因治疗。MSNs 的独特表面特性使其能够进行设计和修饰,以实现核酸的高载药量、免疫系统逃逸、癌细胞靶向、受控货物释放和内涵体逃逸。有报道表明,通过给实验动物的肿瘤部位给予各种能够递送基因的工程化 MSNs,已经取得了成功的治疗效果。本综述详细讨论了通过 MSNs 递送 siRNA、miRNA、shRNA、lncRNA 和 CRISPR/Cas9 的研究,揭示了工程化 MSNs 是一种将基因转移到癌细胞和癌症小鼠模型中的安全有效的系统。

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