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利用外泌体作为下一代生物穿梭载体:对抗 Th17 细胞灾难的下一个最大方法。

Leveraging Exosomes as the Next-Generation Bio-Shuttles: The Next Biggest Approach against Th17 Cell Catastrophe.

机构信息

Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.

出版信息

Int J Mol Sci. 2023 Apr 21;24(8):7647. doi: 10.3390/ijms24087647.

Abstract

In recent years, the launch of clinical-grade exosomes is rising expeditiously, as they represent a new powerful approach for the delivery of advanced therapies and for diagnostic purposes for various diseases. Exosomes are membrane-bound extracellular vesicles that can act as biological messengers between cells, in the context of health and disease. In comparison to several lab-based drug carriers, exosome exhibits high stability, accommodates diverse cargo loads, elicits low immunogenicity and toxicity, and therefore manifests tremendous perspectives in the development of therapeutics. The efforts made to spur exosomes in drugging the untreatable targets are encouraging. Currently, T helper (Th) 17 cells are considered the most prominent factor in the establishment of autoimmunity and several genetic disorders. Current reports have indicated the importance of targeting the development of Th17 cells and the secretion of its paracrine molecule, interleukin (IL)-17. However, the present-day targeted approaches exhibit drawbacks, such as high cost of production, rapid transformation, poor bioavailability, and importantly, causing opportunistic infections that ultimately hamper their clinical applications. To overcome this hurdle, the potential use of exosomes as vectors seem to be a promising approach for Th17 cell-targeted therapies. With this standpoint, this review discusses this new concept by providing a snapshot of exosome biogenesis, summarizes the current clinical trials of exosomes in several diseases, analyzes the prospect of exosomes as an established drug carrier and delineates the present challenges, with an emphasis on their practical applications in targeting Th17 cells in diseases. We further decode the possible future scope of exosome bioengineering for targeted drug delivery against Th17 cells and its catastrophe.

摘要

近年来,临床级别的外泌体迅速问世,因为它们为各种疾病的先进治疗方法和诊断目的提供了一种新的强大方法。外泌体是一种膜结合的细胞外囊泡,在健康和疾病的背景下,可以作为细胞间的生物信使。与几种基于实验室的药物载体相比,外泌体具有高稳定性、可容纳多种货物负载、引起低免疫原性和毒性,因此在治疗学的发展中具有巨大的潜力。为了推动外泌体在治疗不可治疗的靶点方面所做的努力是令人鼓舞的。目前,辅助性 T 细胞(Th)17 细胞被认为是自身免疫和几种遗传疾病建立的最显著因素。目前的报告表明,靶向 Th17 细胞的发展和其旁分泌分子白细胞介素(IL)-17 的分泌的重要性。然而,目前的靶向方法存在一些缺点,如生产成本高、转化迅速、生物利用度差,重要的是,会导致机会性感染,最终阻碍其临床应用。为了克服这一障碍,外泌体作为载体的潜在用途似乎是 Th17 细胞靶向治疗的一种很有前途的方法。基于这一观点,本文通过提供外泌体生物发生的概述,讨论了这一新概念,总结了外泌体在几种疾病中的临床研究,分析了外泌体作为一种已建立的药物载体的前景,并阐述了目前的挑战,重点是它们在疾病中靶向 Th17 细胞的实际应用。我们进一步解码了针对 Th17 细胞的外泌体生物工程靶向药物传递的可能未来范围及其灾难。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c450/10142210/54357ac5e7ff/ijms-24-07647-g001.jpg

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