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工程化的生物异质结,具有感染触发的 H<sub>2</sub>S 释放,用于增强血管生成和感染性皮肤再生。

Engineered Bio-Heterojunction with Infection-Primed H S Liberation for Boosted Angiogenesis and Infectious Cutaneous Regeneration.

机构信息

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, School of Chemical Engineering, Sichuan University, Chengdu, 610065, China.

Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.

出版信息

Small. 2023 Nov;19(45):e2304324. doi: 10.1002/smll.202304324. Epub 2023 Jul 11.

DOI:10.1002/smll.202304324
PMID:37434331
Abstract

Photodynamic therapy (PDT) acts as a powerful weapon against infectious diseases for its enormous antimicrobial activity that quickly elicits storms of reactive oxygen species (ROS). Nevertheless, redundant ROS during treatment inevitably bring detriments in revascularization. To address this dilemma, an innovative P-N bio-heterojunction (bio-HJ) material consisting of p-type copper sulfide (p-CuS), n-type bismuth sulfide (n-Bi S ), and lactate oxidase (LOx) for effective treatment of recalcitrant infectious wounds by promoting angiogenesis is devised. LOx exhausts lactic acid accumulated in infection environment and converts it to hydrogen peroxide (H O ), which subsequently yields bactericidal hydroxyl radicals (·OH) via Fenton-like reactions. Ultimately, the P-N bio-HJs exert synergistic photothermal, photodynamic, and chemodynamic effects for rapid bacterial annihilation. Moreover, in vitro and RNA-seq analyses reveal that the crafted bio-HJs dramatically expedite the proliferation of L929 cells and promote angiogenesis by up-regulating angiogenic gene expression in hypoxia-inducible factor-1 (HIF-1) signaling pathway, which may ascribe to the evolution of H S in response to the infection microenvironment. Critically, results of in vivo experiments have authenticated that the bio-HJs significantly boost healing rates of full-thickness wounds by slaughtering bacteria, elevating angiogenesis, and promoting cytothesis. As envisioned, this work furnishes a novel tactic for the effective treatment of bacteria-invaded wound using H S-liberating P-N bio-HJs.

摘要

光动力疗法(PDT)因其强大的抗菌活性而成为对抗传染病的有力武器,这种活性会迅速引发活性氧(ROS)的爆发。然而,治疗过程中多余的 ROS 不可避免地会对再血管化造成损害。为了解决这一困境,设计了一种创新的 P-N 生物异质结(bio-HJ)材料,由 p 型硫化铜(p-CuS)、n 型硫化铋(n-Bi S )和乳酸氧化酶(LOx)组成,用于通过促进血管生成来有效治疗顽固感染性伤口。LOx 耗尽感染环境中积累的乳酸,并将其转化为过氧化氢(H O ),随后通过芬顿样反应生成杀菌的羟基自由基(·OH)。最终,P-N bio-HJs 发挥协同的光热、光动力和化学动力学效应,实现快速细菌杀灭。此外,体外和 RNA-seq 分析表明,所制备的 bio-HJs 通过上调缺氧诱导因子-1(HIF-1)信号通路中的血管生成基因表达,显著促进 L929 细胞的增殖和血管生成,这可能归因于 H S 对感染微环境的响应而发生的演变。至关重要的是,体内实验结果证实,bio-HJs 通过杀灭细菌、促进血管生成和促进细胞假说,显著提高全层伤口的愈合率。可以预见,这项工作为使用释放 H S 的 P-N bio-HJs 有效治疗细菌感染伤口提供了一种新策略。

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