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负载血管内皮生长因子的活性氧响应性纳米点改善II型糖尿病性周围神经病变中坐骨神经损伤的结构和功能。

VEGF-loaded ROS-responsive nanodots improve the structure and function of sciatic nerve lesions in type II diabetic peripheral neuropathy.

作者信息

Ou Xiaolan, Wang Ze, Yu Daojiang, Guo Wenlai, Zvyagin Andrei V, Lin Quan, Qu Wenrui

机构信息

Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, Jilin, 130041, China; Department of Plastic and Burn Surgery, the Second Affiliated Hospital of Chengdu Medical College, Nuclear Industry 416 Hospital, Chengdu, 610051, China.

State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, 130000, China.

出版信息

Biomaterials. 2025 Apr;315:122906. doi: 10.1016/j.biomaterials.2024.122906. Epub 2024 Oct 26.

Abstract

Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus (DM), significantly contributing to the risk of amputation and mortality. Reactive oxygen species (ROS) can induce both neurological and structural harm through direct impact and pyroptosis, underscoring the critical role of ROS regulation in mitigating DPN. In this research endeavor, we propose harnessing the inherent antioxidant properties of sulfhydryl groups by grafting them onto gold nanodots through an amidation reaction, resulting in the creation of ROS-responsive AuNDs. Additionally, we aim to synthesize AuNDs-VEGF, wherein VEGF is attached to AuNDs via electrostatic interactions, as a therapeutic strategy for addressing DPN in rat models. The results of in vivo experiments showed that AuNDs and AuNDs-VEGF nanoparticles could increase the nerve conduction velocity, shorten the latency of nerve conduction in the sciatic nerve, promote the regeneration of nerve trophectodermal vessels, improve the structure and function of the sciatic nerve, reduce the apoptosis of neural cells, and alleviate the atrophy of the gastrocnemius muscle. Thus, VEGF-loaded ROS-responsive nanodots present a promising avenue for ameliorating diabetic peripheral neuropathy. This innovative approach not only extends the application possibilities of nanodots but also introduces a novel avenue for the treatment of diabetic neuropathy.

摘要

糖尿病周围神经病变(DPN)是糖尿病(DM)的一种常见并发症,显著增加了截肢和死亡风险。活性氧(ROS)可通过直接影响和细胞焦亡诱导神经和结构损伤,凸显了ROS调节在减轻DPN中的关键作用。在本研究中,我们提议通过酰胺化反应将巯基的固有抗氧化特性接枝到金纳米点上,从而制备对ROS有响应的金纳米点(AuNDs)。此外,我们旨在合成AuNDs-VEGF,其中血管内皮生长因子(VEGF)通过静电相互作用附着于AuNDs,作为治疗大鼠模型中DPN的一种策略。体内实验结果表明,AuNDs和AuNDs-VEGF纳米颗粒可提高神经传导速度,缩短坐骨神经神经传导潜伏期,促进神经滋养血管再生,改善坐骨神经的结构和功能,减少神经细胞凋亡,并减轻腓肠肌萎缩。因此,负载VEGF的对ROS有响应的纳米点为改善糖尿病周围神经病变提供了一条有前景的途径。这种创新方法不仅扩展了纳米点的应用可能性,还为糖尿病神经病变的治疗引入了一条新途径。

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