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Updated: Jul 26, 2025
Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Chitosan and Its Structural Modifications for siRNA Delivery
Mona Y Al-Absi1, Anna Eleonora Caprifico1, Gianpiero Calabrese1
1School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Penrhyn Road, Kingston upon Thames, KT1 2EE, United Kingdom.
Abstract:
The use of RNA interference mechanism and small interfering RNA (siRNA) in cancer gene therapy is a very promising approach. However, the success of gene silencing is underpinned by the efficient delivery of intact siRNA into the targeted cell. Nowadays, chitosan is one of the most widely studied non-viral vectors for siRNA delivery, since it is a biodegradable, biocompatible and positively charged polymer able to bind to the negatively charged siRNA forming nanoparticles (NPs) that will act as siRNA delivery system. However, chitosan shows several limitations such as low transfection efficiency and low solubility at physiological pH. Therefore, a variety of chemical and non-chemical structural modifications of chitosan were investigated in the attempt to develop a chitosan derivative showing the features of an ideal siRNA carrier. In this review, the most recently proposed chemical modifications of chitosan are outlined. The type of modification, chemical structure, physicochemical properties, siRNA binding affinity and complexation efficiency of the modified chitosan are discussed. Moreover, the resulting NPs characteristics, cellular uptake, serum stability, cytotoxicity and gene transfection efficiency in vitro and/or in vivo are described and compared to the unmodified chitosan. Finally, a critical analysis of a selection of modifications is included, highlighting the most promising ones for this purpose in the future.
Insights
Modified chitosan shows promise as an efficient carrier for small interfering RNA (siRNA) in cancer gene therapy. Chemical modifications enhance chitosan
Area of Science:
- Biomaterials Science
- Nanotechnology
- Gene Therapy
Background:
- RNA interference (RNAi) using small interfering RNA (siRNA) is a potent strategy for cancer gene therapy.
- Efficient delivery of intact siRNA into target cells is crucial for successful gene silencing.
- Chitosan, a biodegradable polymer, is explored as a non-viral vector for siRNA delivery, but faces limitations like low transfection efficiency and solubility.
Purpose of the Study:
- To review recent chemical modifications of chitosan aimed at improving its properties as an siRNA delivery vector.
- To analyze the impact of these modifications on physicochemical properties, siRNA binding, and nanoparticle characteristics.
- To evaluate the in vitro and in vivo performance of modified chitosan-based siRNA delivery systems.
Main Methods:
- Literature review of recent chemical modifications applied to chitosan for siRNA delivery.
- Discussion of the chemical structures and resulting physicochemical properties of modified chitosans.
- Comparison of modified chitosan-based nanoparticles with unmodified chitosan in terms of complexation, cellular uptake, stability, cytotoxicity, and transfection efficiency.
Main Results:
- Various chemical modifications have been investigated to overcome chitosan's limitations for siRNA delivery.
- Modified chitosans exhibit altered physicochemical properties, influencing siRNA binding and nanoparticle formation.
- Performance evaluations show significant improvements in cellular uptake, serum stability, and gene transfection efficiency for certain modified chitosan derivatives.
Conclusions:
- Chemical modification of chitosan is essential for developing effective siRNA delivery systems for cancer gene therapy.
- Specific modifications offer enhanced properties, leading to improved gene silencing efficacy.
- Further critical analysis is needed to identify the most promising chitosan derivatives for future clinical applications.
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