Al-Absi Mona Y, Caprifico Anna Eleonora, Calabrese Gianpiero
School of Life Sciences, Pharmacy and Chemistry, Kingston University London, Penrhyn Road, Kingston upon Thames, KT1 2EE, United Kingdom.
Adv Pharm Bull. 2023 Mar;13(2):275-282. doi: 10.34172/apb.2023.030. Epub 2022 Jan 8.
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 and/or 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.
在癌症基因治疗中使用RNA干扰机制和小干扰RNA（siRNA）是一种非常有前景的方法。然而，基因沉默的成功取决于完整的siRNA有效递送至靶细胞。如今，壳聚糖是用于siRNA递送研究最广泛的非病毒载体之一，因为它是一种可生物降解、生物相容且带正电荷的聚合物，能够与带负电荷的siRNA结合形成纳米颗粒（NP），这些纳米颗粒将作为siRNA递送系统。然而，壳聚糖存在一些局限性，如转染效率低和在生理pH下溶解度低。因此，人们研究了壳聚糖的各种化学和非化学结构修饰，试图开发出一种具有理想siRNA载体特性的壳聚糖衍生物。在这篇综述中，概述了最近提出的壳聚糖化学修饰。讨论了修饰类型、化学结构、物理化学性质、siRNA结合亲和力和修饰壳聚糖的络合效率。此外，还描述了所得纳米颗粒的特性、细胞摄取、血清稳定性、细胞毒性和基因转染效率，并与未修饰的壳聚糖进行了比较。最后，对一系列修饰进行了批判性分析，突出了未来在此方面最有前景的修饰。
