Targeting Tetraspanins at Cell Interfaces: Functional Modulation and Exosome-Based Drug Delivery for Precise Disease Treatment.

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2024-10-16 DOI:10.1002/cmdc.202400664

Kun Xu, Huixia Feng, Rui Zhao, Yanyan Huang

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Abstract

Tetraspanins are key players in various physiological and pathological processes, including malignancy, immune response, fertilization, and infectious disease. Affinity ligands targeting the interactions between tetraspanins and partner proteins are promising for modulating downstream signaling pathways, thus emerging as attractive candidates for interfering related biological functions. Due to the involvement in vesicle biogenesis and cargo trafficking, tetraspanins are also regarded as exosome markers, and become molecular targets for drug loading and delivery. Given the rapid development in these areas, this minireview focuses on recent advances in design and engineering of affinity binders toward tetraspanins including CD63, CD81, and CD9. Their mechanism of actions in modulating protein interactions at cell interfaces and treatment of malignant diseases are discussed. Strategies for constructing exosome-based drug delivery platforms are also reviewed, with emphasis on the important roles of tetraspanins and the affinity ligands. Finally, challenges and future development of tetraspanin-targeting therapy and exosomal drug delivery platforms are also discussed.

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在细胞界面靶向四泛素：功能调节和基于外泌体的药物输送，实现精准疾病治疗。

四跨蛋白是恶性肿瘤、免疫反应、受精和传染病等各种生理和病理过程中的关键角色。针对四跨蛋白与伙伴蛋白之间相互作用的亲和配体有望调节下游信号通路，因此成为干扰相关生物功能的有吸引力的候选药物。由于参与囊泡生物生成和货物运输，四跨蛋白还被视为外泌体标志物，并成为药物装载和递送的分子靶标。鉴于这些领域的飞速发展，本微综述将重点介绍与 CD63、CD81 和 CD9 等四跨蛋白亲和结合剂的设计和工程方面的最新进展。讨论了它们在调节细胞界面蛋白质相互作用和治疗恶性疾病方面的作用机制。此外，还综述了构建基于外泌体的药物递送平台的策略，重点介绍了四跨蛋白和亲和配体的重要作用。最后，还讨论了四泛素靶向疗法和外泌体给药平台面临的挑战和未来的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.