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Published on: July 21, 2017
Tumor Microenvironment Responsive RNA Drug Delivery Systems: Intelligent Platforms for Sophisticated Release
Guihua Wang1,2, Mengxia Zhang2,3, Weiwei Lai1,2
1Institute of Pharmacy & Pharmacology, University of South China, Hengyang 421001, China.
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.
Insights
This review explores using tumor microenvironment-responsive nanocarriers for RNA gene therapy. These advanced systems improve drug delivery, enhancing cancer treatment effectiveness and safety.
Area of Science:
- Oncology
- Nanotechnology
- Gene Therapy
Background:
- Cancer treatment faces challenges with drug resistance, necessitating novel therapeutic strategies.
- Ribonucleic acid (RNA) gene therapy shows promise for cancer treatment by modulating gene expression, but faces delivery barriers.
- The tumor microenvironment (TME) presents unique characteristics that can be exploited for targeted drug delivery.
Purpose of the Study:
- To review the abnormal components of the TME and their role in tumor survival.
- To discuss the therapeutic potential and mechanisms of RNA-based drugs in cancer.
- To highlight the development and advantages of TME-responsive nanocarriers for RNA delivery in cancer therapy.
Main Methods:
- Discussion of TME characteristics: acidity, hypoxia, enzyme overexpression, glutathione (GSH), and reactive oxygen species (ROS).
- Review of therapeutic RNA roles and underlying mechanisms in cancer.
- Analysis of recent advancements in TME-responsive nanocarrier systems for RNA drug delivery.
Main Results:
- TME-responsive nanocarriers demonstrate effective tumor targeting and reduced toxicity.
- These systems overcome RNA's poor membrane permeability and stability issues.
- Intelligent drug delivery systems can leverage TME features for enhanced therapeutic outcomes.
Conclusions:
- TME-responsive nanocarriers offer a promising strategy for improving RNA gene therapy efficacy in cancer treatment.
- Optimizing these delivery vectors is crucial for overcoming current limitations.
- Further research in this area can lead to safer and more practical cancer treatment options.
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