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Updated: Dec 18, 2025
Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy
Francesco Mainini1, Michael R Eccles1
1Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand.
Abstract:
RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient's therapeutic response.
Insights
RNA interference (RNAi) therapy uses small interfering RNAs (siRNAs) to silence genes for cancer treatment. Nanoparticle delivery systems are crucial for overcoming biological barriers and enabling effective siRNA delivery in vivo.
Area of Science:
- Biomedical Engineering
- Oncology
- Molecular Biology
Background:
- RNA interference (RNAi) utilizes small interfering RNAs (siRNAs) for gene silencing, presenting a promising avenue for cancer therapy.
- Efficient in vivo delivery of siRNAs into tumor cells and the tumor micro-environment (TME) faces significant physiological barriers.
- Nanoparticle-based delivery systems, utilizing lipids and polymers, are key to overcoming these barriers for effective RNAi therapy.
Purpose of the Study:
- To review strategies for overcoming physiological barriers in siRNA delivery for cancer therapy.
- To discuss various lipid and polymer-based carriers used in nanoparticle siRNA delivery systems.
- To examine current clinical trials and future prospects of siRNA-based cancer therapeutics.
Main Methods:
- Review of literature on siRNA delivery systems and their application in cancer therapy.
- Analysis of strategies for enhancing siRNA stability, tissue penetration, and cellular uptake.
- Discussion of nanoparticle formulations, including lipid and polymer-based carriers.
- Examination of anti-tumor nanovaccines and clinical trial data.
Main Results:
- Nanoparticle systems effectively enhance siRNA survival, facilitate tumor targeting, and promote cellular uptake.
- Lipid and polymer-based carriers demonstrate versatility in delivering siRNAs for cancer treatment.
- Emerging strategies include siRNA-enhanced nanovaccines and combination therapies with immune checkpoint inhibitors.
Conclusions:
- Nanoparticle-mediated siRNA delivery is critical for advancing RNAi-based cancer therapeutics.
- Continued research and clinical trials are essential for realizing the full potential of siRNA therapy.
- Precision cancer medicine may integrate gene-targeting siRNAs with other therapies for personalized treatment outcomes.
