Tumor Microenvironment Responsive RNA Drug Delivery Systems: Intelligent Platforms for Sophisticated Release.

IF 4.5 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Pharmaceutics Pub Date : 2024-09-02 Epub Date: 2024-07-26 DOI:10.1021/acs.molpharmaceut.4c00334

Guihua Wang, Mengxia Zhang, Weiwei Lai, Yuan Gao, Shuxian Liao, Qian Ning, Shengsong Tang

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Abstract

Cancer is a significant health concern, increasingly showing insensitivity to traditional treatments, highlighting the urgent need for safer and more practical treatment options. Ribonucleic acid (RNA) gene therapy drugs have demonstrated promising potential in preclinical and clinical trials for antitumor therapy by regulating tumor-related gene expression. However, RNA's poor membrane permeability and stability restrict its effectiveness in entering and being utilized in cells. An appropriate delivery system is crucial for achieving targeted tumor effects. The tumor microenvironment (TME), characterized by acidity, hypoxia, enzyme overexpression, elevated glutathione (GSH) concentration, and excessive reactive oxygen species (ROS), is essential for tumor survival. Furthermore, these distinctive features can also be harnessed to develop intelligent drug delivery systems. Various nanocarriers that respond to the TME have been designed for RNA drug delivery, showing the advantages of tumor targeting and low toxicity. This Review discusses the abnormal changes of components in TME, therapeutic RNAs' roles, underlying mechanisms, and the latest developments in utilizing vectors that respond to microenvironments for treating tumors. We hope it provides insight into creating and optimizing RNA delivery vectors to improve their effectiveness.

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肿瘤微环境响应 RNA 给药系统：复杂释放的智能平台。

癌症是一个重大的健康问题，对传统疗法越来越不敏感，因此迫切需要更安全、更实用的治疗方案。核糖核酸（RNA）基因治疗药物通过调节肿瘤相关基因的表达，在临床前和临床试验中显示出抗肿瘤治疗的巨大潜力。然而，由于 RNA 的膜渗透性和稳定性较差，限制了其进入细胞并在细胞内被利用的有效性。适当的递送系统对于实现肿瘤靶向效应至关重要。肿瘤微环境（TME）以酸性、缺氧、酶过表达、谷胱甘肽（GSH）浓度升高和活性氧（ROS）过多为特征，对肿瘤的生存至关重要。此外，还可以利用这些独特的特征来开发智能给药系统。目前已设计出多种响应 TME 的纳米载体用于 RNA 药物递送，显示出肿瘤靶向性和低毒性的优势。本综述探讨了肿瘤微环境中各成分的异常变化、治疗 RNA 的作用、内在机制以及利用响应微环境的载体治疗肿瘤的最新进展。我们希望这篇综述能为创建和优化 RNA 运送载体以提高其有效性提供启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Pharmaceutics 医学-药学

CiteScore

8.00

自引率

6.10%

发文量

391

审稿时长

2 months

期刊介绍： Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.