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明胶酶响应型可生物降解靶向微针贴片用于金黄色葡萄球菌感染脓肿伤口治疗。

Gelatinase-responsive biodegradable targeted microneedle patch for abscess wound treatment of S. aureus infection.

机构信息

Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, PR China.

Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei, PR China; Key Laboratory of Biomedical Photonics (HUST), Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074, Hubei, PR China.

出版信息

Int J Biol Macromol. 2023 Dec 31;253(Pt 8):127548. doi: 10.1016/j.ijbiomac.2023.127548. Epub 2023 Oct 19.

Abstract

Abscess wound caused by bacterial infection is usually difficult to heal, thus greatly affect people's quality of life. In this study, a biodegradable drug-loaded microneedle patch (MN) is designed for targeted eradication of S. aureus infection and repair of abscess wound. Firstly, the bacterial responsive composite nanoparticle (Ce6@GNP-Van) with a size of about 182.6 nm is constructed by loading the photosensitizer Ce6 into gelatin nanoparticle (GNP) and coupling vancomycin (Van), which can specifically target S. aureus and effectively shield the phototoxicity of photosensitizer during delivery. When Ce6@GNP-Van is targeted and enriched in the infected regions, the gelatinase secreted by the bacteria can degrade GNP in situ and release Ce6, which can kill the bacteria by generating ROS under laser irradiation. In vivo experiments show that the microneedle is basically degraded in 10 min after inserting into skin, and the abscess wound is completely healed within 13 d after applying Ce6@GNP-Van-loaded MN patch to the abscess wound of the bacterial infected mice with laser irradiation, which can simultaneously achieve the eradication of biofilm and subsequent wound healing cascade activation, showing excellent synergistic antibacterial effect. In conclusion, this work establishes a synergistic treatment strategy to facilitate the repair of chronic abscess wound.

摘要

由细菌感染引起的脓肿伤口通常难以愈合,从而极大地影响了人们的生活质量。在本研究中,设计了一种可生物降解的载药微针贴片(MN),用于靶向消除金黄色葡萄球菌感染和修复脓肿伤口。首先,构建了尺寸约为 182.6nm 的细菌响应型复合纳米颗粒(Ce6@GNP-Van),将光敏剂 Ce6 装载到明胶纳米颗粒(GNP)中,并偶联万古霉素(Van),可以特异性靶向金黄色葡萄球菌,并在递药过程中有效屏蔽光敏剂的光毒性。当 Ce6@GNP-Van 被靶向并在感染区域富集时,细菌分泌的明胶酶可以原位降解 GNP 并释放 Ce6,在激光照射下产生 ROS 杀死细菌。体内实验表明,微针插入皮肤后基本在 10min 内完全降解,在激光照射下将载有 Ce6@GNP-Van 的 MN 贴片应用于金黄色葡萄球菌感染小鼠的脓肿伤口后,脓肿伤口在 13d 内完全愈合,同时实现了生物膜的消除和随后的伤口愈合级联激活,表现出优异的协同抗菌作用。总之,这项工作建立了一种协同治疗策略,有助于慢性脓肿伤口的修复。

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