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外泌体介导的siRNA分子在癌症治疗中的应用:成就与挑战

Exosome-mediated delivery of siRNA molecules in cancer therapy: triumphs and challenges.

作者信息

Ubanako Philemon, Mirza Sheefa, Ruff Paul, Penny Clement

机构信息

Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

出版信息

Front Mol Biosci. 2024 Sep 17;11:1447953. doi: 10.3389/fmolb.2024.1447953. eCollection 2024.

Abstract

The discovery of novel and innovative therapeutic strategies for cancer treatment and management remains a major global challenge. Exosomes are endogenous nanoscale extracellular vesicles that have garnered increasing attention as innovative vehicles for advanced drug delivery and targeted therapy. The attractive physicochemical and biological properties of exosomes, including increased permeability, biocompatibility, extended half-life in circulation, reduced toxicity and immunogenicity, and multiple functionalization strategies, have made them preferred drug delivery vehicles in cancer and other diseases. Small interfering RNAs (siRNAs) are remarkably able to target any known gene: an attribute harnessed to knock down cancer-associated genes as a viable strategy in cancer management. Extensive research on exosome-mediated delivery of siRNAs for targeting diverse types of cancer has yielded promising results for anticancer therapy, with some formulations progressing through clinical trials. This review catalogs recent advances in exosome-mediated siRNA delivery in several types of cancer, including the manifold benefits and minimal drawbacks of such innovative delivery systems. Additionally, we have highlighted the potential of plant-derived exosomes as innovative drug delivery systems for cancer treatment, offering numerous advantages such as biocompatibility, scalability, and reduced toxicity compared to traditional methods. These exosomes, with their unique characteristics and potential for effective siRNA delivery, represent a significant advancement in nanomedicine and cancer therapeutics. Further exploration of their manufacturing processes and biological mechanisms could significantly advance natural medicine and enhance the efficacy of exosome-based therapies.

摘要

发现用于癌症治疗和管理的新颖创新治疗策略仍然是一项重大的全球挑战。外泌体是内源性纳米级细胞外囊泡,作为先进药物递送和靶向治疗的创新载体,已受到越来越多的关注。外泌体具有吸引人的物理化学和生物学特性,包括通透性增加、生物相容性好、循环半衰期延长、毒性和免疫原性降低以及多种功能化策略,使其成为癌症和其他疾病中首选的药物递送载体。小干扰RNA(siRNAs)能够显著靶向任何已知基因:这一特性被用于敲低癌症相关基因,作为癌症管理中的一种可行策略。对外泌体介导的siRNAs递送用于靶向多种类型癌症的广泛研究已在抗癌治疗中取得了有希望的结果,一些制剂已进入临床试验阶段。本综述列举了外泌体介导的siRNAs递送至几种癌症类型的最新进展,包括此类创新递送系统的诸多益处和极小的缺点。此外,我们强调了植物来源的外泌体作为癌症治疗创新药物递送系统的潜力,与传统方法相比,它具有生物相容性、可扩展性和毒性降低等诸多优势。这些外泌体具有独特的特性和有效递送siRNAs的潜力,代表了纳米医学和癌症治疗学的重大进展。对其制造过程和生物学机制的进一步探索可能会显著推动天然药物的发展,并提高基于外泌体疗法的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c40f/11442288/45b694caa7dd/fmolb-11-1447953-g001.jpg

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