An integrated "Engage & Evasion" approach for mononuclear phagocyte system escape and efficient extracellular vesicle therapy.

IF 10.6 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Hongman Liu, Mengting Li, Bing Xiang, Ziying Yang, Shiyu Cao, Wen Gong, Jingjing Li, Wenjing Zhou, Liang Ding, Qingsong Tang, Shengnan Wang, Jin Tang, Zixuan Fan, Ke He, Xuan Jiang, Zhenya Shen, Weiqian Chen, Jie Hui
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引用次数: 0

Abstract

Ischemic diseases are major contributors to global morbidity and mortality, posing a substantial threat to human health. Extracellular vesicles (EVs) play an essential role in enhancing neovascularization in ischemic tissues, thereby facilitating tissue repair and regeneration. However, the utilization of EVs is hindered by their rapid uptake and clearance by the mononuclear phagocyte system (MPS), which markedly impedes their therapeutic efficacy and organ-specific accumulation. Notably, CD47, upon binding to signal regulatory protein alpha, initiates a "don't eat me" signal, enabling immune evasion from the MPS. Our research has demonstrated that phagocytes predominantly engulf CD47low dendritic DC2.4 cell-derived EVs (DV), while engineered CD47high EVs (MV47) experience minimal ingestion. Leveraging these findings, we have developed a dual-faceted "Engage & Evasion" strategy. Initially, DVs were employed to saturate the MPS, serving as the "engage" component. Subsequently, MV47, fortified with CD47, was introduced for "evasion" purposes. This approach effectively minimized entrapment by the liver and spleen, boosted serum concentration, and enhanced final accumulation in non-MPS organs. In summary, our "Engage & Evasion" therapeutic strategy offers a promising avenue to enhance EV therapeutic potential against ischemic challenges through improved systemic distribution.

单核吞噬细胞系统逃逸和高效细胞外囊泡治疗的综合“介入&逃避”方法。
缺血性疾病是全球发病率和死亡率的主要原因,对人类健康构成重大威胁。细胞外囊泡(Extracellular vesicles, EVs)在促进缺血组织的新生血管形成,从而促进组织修复和再生方面发挥着重要作用。然而,ev的利用受到其被单核吞噬细胞系统(MPS)快速摄取和清除的阻碍,这明显阻碍了其治疗效果和器官特异性积累。值得注意的是,CD47与信号调节蛋白α结合后,启动“不要吃我”信号,使免疫逃避MPS。我们的研究表明,吞噬细胞主要吞噬cd47低的树突状DC2.4细胞源性ev (DV),而工程化cd47高的ev (MV47)则被最小的摄入。利用这些发现,我们制定了一个双重的“参与与逃避”战略。最初,使用DVs来饱和MPS,作为“接合”组件。随后,加入CD47的MV47被引入以“逃避”。这种方法有效地减少了肝脏和脾脏的夹带,提高了血清浓度,并增强了非mps器官的最终积累。总之,我们的“参与&逃避”治疗策略提供了一个有希望的途径,通过改善全身分布来增强EV治疗缺血性挑战的潜力。
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
Journal of Nanobiotechnology
Journal of Nanobiotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-NANOSCIENCE & NANOTECHNOLOGY
CiteScore
13.90
自引率
4.90%
发文量
493
审稿时长
16 weeks
期刊介绍: Journal of Nanobiotechnology is an open access peer-reviewed journal communicating scientific and technological advances in the fields of medicine and biology, with an emphasis in their interface with nanoscale sciences. The journal provides biomedical scientists and the international biotechnology business community with the latest developments in the growing field of Nanobiotechnology.
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