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Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Research Progress on Polymer-Based Nanocarriers for Tumor-Targeted Delivery of Survivin siRNA
Luya Ren1,2, Shaoxia Wang2, Bin-Chun Li1
1Institute of Biotechnology, Shanxi University, Taiyuan 030006, China.
Abstract:
Survivin, a pivotal member of the inhibitor of apoptosis proteins (IAP) family, plays critical roles in cell cycle regulation and division. Survivin is overexpressed in most malignancies, making it an attractive therapeutic target. Due to its high specificity and potency, siRNA-based RNA interference (RNAi) has emerged as a powerful therapeutic strategy for effectively downregulating disease-related genes such as survivin in cancer therapy. However, naked siRNA suffers from rapid enzymatic degradation, poor cellular uptake, and off-target effects, severely limiting its therapeutic efficacy in vivo. Development of polymer-based nanocarriers for tumor-targeted delivery of survivin siRNA (siSurvivin) holds great potential to address these challenges. In this review, we first described the structure and function of survivin and summarized the survivin-targeted therapeutic strategy. Then, the siRNA delivery systems, particularly the polymeric nanocarriers, were introduced. Furthermore, a plethora of polymer-based nanocarriers for tumor-targeted siSurvivin delivery, including synthetic polymers (branched polymers, dendritic polymers, polymeric micelles), natural polymers (polysaccharides, proteins, and others), lipid-polymer hybrid nanoparticles, and polymer composite nanoparticles, were elaborated. Promising results underscore the potential of polymer-based nanocarriers for survivin siRNA delivery to enhance cancer therapy, providing a roadmap for future clinical translation.
Insights
Polymer-based nanocarriers show promise for delivering survivin siRNA (siSurvivin) to tumors. This approach overcomes naked siRNA limitations, enhancing cancer therapy and paving the way for clinical translation.
Area of Science:
- Biomedical Engineering
- Cancer Therapeutics
- Molecular Biology
Background:
- Survivin, an inhibitor of apoptosis protein, is overexpressed in many cancers, making it a key therapeutic target.
- Small interfering RNA (siRNA) offers specific gene silencing but faces challenges like degradation and poor delivery in vivo.
- Polymer-based nanocarriers are being developed to enhance the delivery and efficacy of survivin siRNA (siSurvivin).
Purpose of the Study:
- To review the role of survivin in cancer and its therapeutic targeting.
- To explore the potential of polymer-based nanocarriers for tumor-targeted delivery of siSurvivin.
- To provide a roadmap for the clinical translation of this cancer therapy strategy.
Main Methods:
- Review of literature on survivin structure, function, and targeted therapies.
- Introduction to siRNA delivery systems, focusing on polymeric nanocarriers.
- Elaboration on various polymer-based nanocarriers for siSurvivin delivery, including synthetic, natural, hybrid, and composite types.
Main Results:
- Polymer-based nanocarriers demonstrate potential for overcoming naked siSurvivin limitations.
- Various nanocarrier systems (synthetic, natural, hybrid, composite) show promise for tumor-targeted delivery.
- Promising preclinical results highlight the therapeutic potential of these delivery systems.
Conclusions:
- Polymer-based nanocarriers represent a promising strategy for enhancing cancer therapy via survivin siRNA delivery.
- This approach addresses key challenges associated with naked siRNA, improving therapeutic efficacy.
- Further development and clinical translation of these nanocarrier systems are warranted.
