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外泌体在肿瘤生长、化疗耐药和免疫中的作用:最新进展。

Role of exosomes in tumour growth, chemoresistance and immunity: state-of-the-art.

机构信息

Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

J Drug Target. 2023 Jan;31(1):32-50. doi: 10.1080/1061186X.2022.2114000. Epub 2022 Aug 21.

Abstract

Cancer is one of the most lethal diseases, and limited available treatment options contribute to its high mortality rate. Exosomes are considered membrane-bound nanovesicles that include different molecules such as lipids, proteins, and nucleic acids. Virtually most cells could release exosomes exocytosis in physiological and pathological conditions. Tumour-derived exosomes (TDEs) play essential roles in tumorigenesis, proliferation, progression, metastasis, immune escape, and chemoresistance by transferring functional biological cargos, triggering different autocrine, and paracrine signalling cascades. Due to their antigen-presenting properties, exosomes are widely used as biomarkers and drug carriers and have a prominent role in cancer immunotherapy. They offer various advantages in carrier systems (e.g. in chemotherapy, siRNA, and miRNA), delivery of diagnostic agents owing to their stability, loading of hydrophobic and hydrophilic agents, and drug targeting. Novel exosomes-based carriers can be generated as intelligent systems using various sources and crosslinking chemistry extracellular vesicles (EVs). Exosomes studded with targeting ligands, including peptides, can impart in targeted delivery of cargos to tumour cells. In this review, we comprehensively summarised the important role of tumour-derived exosomes in dictating cancer pathogenesis and resistance to therapy. We have therefore, investigated in further detail the pivotal role of tumour-derived exosomes in targeting various cancer cells and their applications, and prospects in cancer therapy and diagnosis. Additionally, we have implicated the potential utility and significance of tumour exosomes-based nanoparticles as an efficient and novel therapeutic carrier and their applications in treating advanced cancers.

摘要

癌症是最致命的疾病之一,有限的可用治疗选择导致其高死亡率。外泌体被认为是包含不同分子(如脂质、蛋白质和核酸)的膜结合纳米囊泡。实际上,大多数细胞在生理和病理条件下都可以通过胞吐作用释放外泌体。肿瘤来源的外泌体(TDEs)通过传递功能性生物货物,触发不同的自分泌和旁分泌信号级联,在肿瘤发生、增殖、进展、转移、免疫逃逸和化疗耐药中发挥重要作用。由于其抗原呈递特性,外泌体被广泛用作生物标志物和药物载体,并在癌症免疫治疗中发挥重要作用。它们在载体系统(如化疗、siRNA 和 miRNA)中具有各种优势,由于其稳定性、疏水性和亲水性药物的负载以及药物靶向性,可用于递送诊断剂。新型基于外泌体的载体可以使用各种来源和交联化学方法生成智能系统。外泌体上镶嵌有靶向配体,如肽,可将货物靶向递送到肿瘤细胞。在这篇综述中,我们全面总结了肿瘤来源的外泌体在决定癌症发病机制和对治疗的耐药性方面的重要作用。因此,我们进一步详细研究了肿瘤来源的外泌体在靶向各种癌细胞及其应用,以及在癌症治疗和诊断中的应用前景。此外,我们还暗示了基于肿瘤外泌体的纳米粒子作为一种有效和新型治疗载体的潜在应用和意义,及其在治疗晚期癌症中的应用。

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