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Published on: May 2, 2019
Nanoparticles-Based Strategies to Improve the Delivery of Therapeutic Small Interfering RNA in Precision Oncology
Jinxing Huang1,2, Kai Xiao1,2
1Precision Medicine Research Center, Sichuan Provincial Key Laboratory of Precision Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China.
Abstract:
Small interfering RNA (siRNA) can selectively suppress the expression of disease-causing genes, holding great promise in the treatment of human diseases, including malignant cancers. In recent years, with the development of chemical modification and delivery technology, several siRNA-based therapeutic drugs have been approved for the treatment of non-cancerous liver diseases. Nevertheless, the clinical development of siRNA-based cancer therapeutics remains a major translational challenge. The main obstacles of siRNA therapeutics in oncology include both extracellular and intracellular barriers, such as instability under physiological conditions, insufficient tumor targeting and permeability (particularly for extrahepatic tumors), off-target effects, poor cellular uptake, and inefficient endosomal escape. The development of clinically suitable and effective siRNA delivery systems is expected to overcome these challenges. Herein, we mainly discuss recent strategies to improve the delivery and efficacy of therapeutic siRNA in cancer, including the application of non-viral nanoparticle-based carriers, the selection of target genes for therapeutic silencing, and the combination with other therapeutic modalities. In addition, we also provide an outlook on the ongoing challenges and possible future developments of siRNA-based cancer therapeutics during clinical translation.
Insights
Small interfering RNA (siRNA) offers promise for cancer treatment by silencing disease genes. Overcoming delivery barriers with advanced systems is key to advancing siRNA cancer therapeutics.
Area of Science:
- Biotechnology
- Molecular Biology
- Oncology
Background:
- Small interfering RNA (siRNA) selectively suppresses gene expression, showing therapeutic potential for diseases, including cancer.
- Approved siRNA drugs exist for non-cancerous liver diseases, but clinical translation for cancer remains challenging.
- Key obstacles for siRNA cancer therapeutics include instability, poor tumor targeting, off-target effects, and inefficient cellular delivery.
Purpose of the Study:
- To review recent strategies for enhancing siRNA delivery and efficacy in cancer treatment.
- To discuss the role of nanoparticle carriers, target gene selection, and combination therapies.
- To provide an outlook on challenges and future directions for clinical translation of siRNA cancer therapeutics.
Main Methods:
- Review of recent literature on siRNA delivery systems for cancer.
- Analysis of strategies involving non-viral nanoparticle carriers.
- Discussion of target gene selection and combination therapeutic approaches.
Main Results:
- Nanoparticle-based carriers show potential for improving siRNA delivery and overcoming biological barriers.
- Strategic selection of target genes and combination therapies can enhance therapeutic outcomes.
- Significant progress has been made in addressing delivery challenges, though clinical translation requires further development.
Conclusions:
- Effective siRNA delivery systems are crucial for overcoming extracellular and intracellular barriers in cancer therapy.
- Continued innovation in delivery technology, target identification, and combination strategies is essential for advancing siRNA cancer therapeutics.
- Addressing current challenges will pave the way for successful clinical translation of siRNA-based cancer treatments.
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