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用于 siRNA 递送和基因治疗的智能物理化学触发的壳聚糖基纳米凝胶:聚焦癌症治疗的新兴策略和范例

Smart Physicochemical-triggered Chitosan-based Nanogels for siRNA Delivery and Gene Therapy: A Focus on Emerging Strategies and Paradigms for Cancer Therapy.

作者信息

Naghib Seyed Morteza, Ahmadi Bahar, Mozafari M R

机构信息

Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology (IUST), Tehran, 1684613114, Iran.

Biomaterials and Tissue Engineering Research Group, Interdisciplinary Technologies Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.

出版信息

Curr Med Chem. 2024 Jun 5. doi: 10.2174/0109298673286052240426044945.

DOI:10.2174/0109298673286052240426044945
PMID:38847253
Abstract

Cancer therapy has seen significant advancements in recent years, with the emergence of RNA interference (RNAi) as a promising strategy for targeted gene silencing. However, the successful delivery of small interfering RNA (siRNA) to cancer cells remains a challenge. Chitosan nanoparticles (CSNPs) can be derived from the natural polysaccharide chitin sources. CSNPs have gained considerable attention as a potential solution to encapsulate siRNA due to their biocompatibility, and biodegradability. This article explores the application of CSNPs for siRNA delivery in cancer therapy. Firstly, it discusses the significance of siRNA in gene regulation and highlights its potential to selectively silence oncogenes or tumor suppressor genes, making it a powerful tool in cancer treatment. The obstacles associated with effective siRNA delivery, such as degradation by nucleases and poor cellular uptake, are also addressed. Next, the focus shifts to the unique properties of CSNPs that make them attractive for siRNA delivery. The discussion revolves around how chitosan can interact electrostatically with siRNA to create stable complexes, as well as the controlled release of siRNA from CSNPs. This controlled release ensures sustained and efficient delivery of siRNA to cancer cells, maximizing therapeutic efficacy. Moreover, the biocompatibility and biodegradability of CSNPs make them ideal for in vivo applications. Different approaches to modifying and functionalizing surfaces are investigated by emphasizing on enhancement of stability and targeting abilities of CSNPs in cancer treatment. Registered trials for CS and siRNA are summarized, along with ongoing investigations into various applications of chitosan in medical treatments. Overall, the application of CSNPs in siRNA delivery for cancer therapy holds great promise and offers a potential solution to overcome the challenges associated with RNAi-based treatments. Continued advancements in this field will likely lead to improved targeted therapies with reduced side effects, ultimately benefitting cancer patients worldwide.

摘要

近年来,癌症治疗取得了显著进展,RNA干扰(RNAi)作为一种有前景的靶向基因沉默策略应运而生。然而,将小干扰RNA(siRNA)成功递送至癌细胞仍然是一项挑战。壳聚糖纳米颗粒(CSNPs)可从天然多糖几丁质来源获得。由于其生物相容性和可生物降解性,CSNPs作为封装siRNA的潜在解决方案受到了广泛关注。本文探讨了CSNPs在癌症治疗中用于siRNA递送的应用。首先,讨论了siRNA在基因调控中的重要性,并强调了其选择性沉默癌基因或肿瘤抑制基因的潜力,使其成为癌症治疗中的有力工具。还讨论了与有效siRNA递送相关的障碍,如被核酸酶降解和细胞摄取不良。接下来,重点转向CSNPs使其对siRNA递送具有吸引力的独特性质。讨论围绕壳聚糖如何与siRNA静电相互作用以形成稳定复合物,以及siRNA从CSNPs中的控释。这种控释确保了siRNA持续有效地递送至癌细胞,从而使治疗效果最大化。此外,CSNPs的生物相容性和可生物降解性使其非常适合体内应用。通过强调增强CSNPs在癌症治疗中的稳定性和靶向能力,研究了不同的表面修饰和功能化方法。总结了壳聚糖和siRNA的注册试验,以及对壳聚糖在医学治疗中各种应用的 ongoing investigations。总体而言,CSNPs在癌症治疗的siRNA递送中的应用具有很大潜力,并为克服基于RNAi的治疗相关挑战提供了潜在解决方案。该领域的持续进展可能会带来副作用减少的改进靶向疗法,最终使全球癌症患者受益。

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Modification of BCLX pre-mRNA splicing has antitumor efficacy alone or in combination with radiotherapy in human glioblastoma cells.BCLX 前体 mRNA 剪接的修饰单独或联合放疗在人胶质母细胞瘤细胞中具有抗肿瘤疗效。
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Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy.通过靶向 CD44 的纳米载体抑制 iRhom1 以改善癌症免疫化疗。
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Straight to the point: targeted mRNA-delivery to immune cells for improved vaccine design.
直切要点:靶向免疫细胞的 mRNA 递送,用于改良疫苗设计。
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Chitosan and Its Structural Modifications for siRNA Delivery.用于小干扰RNA递送的壳聚糖及其结构修饰
Adv Pharm Bull. 2023 Mar;13(2):275-282. doi: 10.34172/apb.2023.030. Epub 2022 Jan 8.
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Recent Advances in Chitosan-Based Applications-A Review.基于壳聚糖应用的最新进展——综述
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Nanomedicine for Cancer.癌症的纳米医学
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