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壳聚糖基纳米递药系统在生物医学中的应用:在癌症治疗中siRNA 递呈的潜在用途。

Biomedical application of chitosan-based nanoscale delivery systems: Potential usefulness in siRNA delivery for cancer therapy.

机构信息

Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956 Istanbul, Turkey; Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Üniversite Caddesi No. 27, Orhanlı, Tuzla, 34956 Istanbul, Turkey.

Department of Chemical Sciences, University of Naples "Federico II", Complesso Universitario Monte S. Angelo, Via Cintia, 80126 Naples, Italy.

出版信息

Carbohydr Polym. 2021 May 15;260:117809. doi: 10.1016/j.carbpol.2021.117809. Epub 2021 Feb 16.

Abstract

Gene therapy is an emerging and promising strategy in cancer therapy where small interfering RNA (siRNA) system has been deployed for down-regulation of targeted gene and subsequent inhibition in cancer progression; some issues with siRNA, however, linger namely, its off-targeting property and degradation by enzymes. Nanoparticles can be applied for the encapsulation of siRNA thus enhancing its efficacy in gene silencing where chitosan (CS), a linear alkaline polysaccharide derived from chitin, with superb properties such as biodegradability, biocompatibility, stability and solubility, can play a vital role. Herein, the potential of CS nanoparticles has been discussed for the delivery of siRNA in cancer therapy; proliferation, metastasis and chemoresistance are suppressed by siRNA-loaded CS nanoparticles, especially the usage of pH-sensitive CS nanoparticles. CS nanoparticles can provide a platform for the co-delivery of siRNA and anti-tumor agents with their enhanced stability via chemical modifications. As pre-clinical experiments are in agreement with potential of CS-based nanoparticles for siRNA delivery, and these carriers possess biocompatibiliy and are safe, further studies can focus on evaluating their utilization in cancer patients.

摘要

基因治疗是癌症治疗中一种新兴且有前途的策略,其中小干扰 RNA (siRNA) 系统已被用于下调靶向基因,并随后抑制癌症进展;然而,siRNA 存在一些问题,例如脱靶效应和被酶降解。纳米粒子可用于封装 siRNA,从而提高其基因沉默的功效,其中壳聚糖 (CS) 是一种源自几丁质的线性碱性多糖,具有生物降解性、生物相容性、稳定性和溶解性等优异性能,可发挥重要作用。本文讨论了 CS 纳米粒子在癌症治疗中递送 siRNA 的潜力;负载 siRNA 的 CS 纳米粒子可抑制细胞增殖、转移和化疗耐药性,尤其是使用 pH 敏感的 CS 纳米粒子。CS 纳米粒子可通过化学修饰提供一个平台,用于共递送 siRNA 和抗肿瘤药物,并增强其稳定性。由于临床前实验与基于 CS 的纳米粒子在 siRNA 递送上的潜力一致,并且这些载体具有生物相容性和安全性,因此可以进一步研究其在癌症患者中的应用。

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