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使用磁响应趋化纳米马达增强外泌体向腹主动脉瘤的递送以进行弹性基质再生修复

Enhancing Exosomal Delivery to Abdominal Aortic Aneurysms using Magnetically Responsive Chemotactic Nanomotors for Elastic Matrix Regenerative Repair.

作者信息

Wang Lulu, Zhang Yao, Mao Chun, Li Xiaoqiang

机构信息

Department of Vascular Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, 210008, China.

National and Local Joint Engineering Research Center of Biomedical Functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, Jiangsu, 210023, China.

出版信息

Adv Sci (Weinh). 2024 Dec;11(46):e2405085. doi: 10.1002/advs.202405085. Epub 2024 Oct 21.

Abstract

Abdominal aortic aneurysms (AAAs) involve localized dilation of the abdominal aorta, with the reversal of this condition being significantly limited by the inherently poor and abnormal regenerative repair of the aortic elastic matrix. Mesenchymal stem cell exosomes (MSCEs) are promising regenerative tools; however, achieving precise targeting of AAA with MSCEs is challenging owing to the high blood flow in the arterial system. In this study, an engineered exosomal nanomotor is developed for magnetic and chemical propulsion. The results demonstrate that this nanomotor effectively enhances the delivery of MSCEs to the AAA through magnetic field navigation and catalase-induced chemotaxis. The nanomotor significantly enhances the elastic matrix repair, reduces oxidative stress, and activates the PI3K/Akt pathway, leading to aneurysm shrinkage and reversal. In addition, the nanomotor possesses magnetic resonance imaging capabilities. The use of this nanomotor offers a novel, targeted drug delivery system in a rat model of AAA and holds promise as a potential therapeutic option for this condition.

摘要

腹主动脉瘤(AAA)涉及腹主动脉的局部扩张,而由于主动脉弹性基质固有的不良和异常再生修复,这种情况的逆转受到显著限制。间充质干细胞外泌体(MSCEs)是很有前景的再生工具;然而,由于动脉系统中血流速度快,利用MSCEs实现对AAA的精准靶向具有挑战性。在本研究中,开发了一种用于磁驱动和化学驱动的工程化外泌体纳米马达。结果表明,这种纳米马达通过磁场导航和过氧化氢酶诱导的趋化作用有效地增强了MSCEs向AAA的递送。该纳米马达显著增强了弹性基质修复,降低了氧化应激,并激活了PI3K/Akt通路,导致动脉瘤缩小和逆转。此外,该纳米马达具有磁共振成像能力。在AAA大鼠模型中使用这种纳米马达提供了一种新型的靶向给药系统,有望成为治疗这种疾病的潜在选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6acd/11633499/8c7343c529c7/ADVS-11-2405085-g003.jpg

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