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基于富含缺陷的多纳米酶的可注射水凝胶通过氧气自供应级联反应促进糖尿病伤口愈合。

Injectable Hydrogel Based on Defect-Rich Multi-Nanozymes for Diabetic Wound Healing via an Oxygen Self-Supplying Cascade Reaction.

机构信息

Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an, Shaanxi, 710069, China.

Shaanxi R&D Centre of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an, Shaanxi, 710069, China.

出版信息

Small. 2022 May;18(18):e2200165. doi: 10.1002/smll.202200165. Epub 2022 Apr 3.

DOI:10.1002/smll.202200165
PMID:35373522
Abstract

Diabetic wound healing remains challenging owing to the risk for bacterial infection, hypoxia, excessive glucose levels, and oxidative stress. Glucose-activated cascade reactions can consume glucose and eradicate bacteria, avoiding the direct use of hydrogen peroxide (H O ) and wound pH restriction on peroxidase-like activity. However, the anoxic microenvironment in diabetic wounds impedes the cascade reaction due to the oxygen (O ) dependence of glucose oxidation. Herein, defect-rich molybdenum disulfide nanosheets loaded with bovine serum albumin-modified gold nanoparticle (MoS @Au@BSA NSs) heterostructures are designed and anchored onto injectable hydrogels to promote diabetic wound healing through an O self-supplying cascade reaction. BSA decoration decreases the particle size of Au, increasing the activity of multiple enzymes. Glucose oxidase-like Au catalyzes the oxidation of glucose into gluconic acid and H O , which is transformed into a hydroxyl radical (•OH) catalyzed by peroxidase-like MoS @Au@BSA to eradicate bacteria. When the wound pH reaches an alkalescent condition, MoS @Au@BSA mimicks superoxide dismutase to transform superoxide anions into O and H O , and decomposes endogenous and exogenous H O into O via catalase-like mechanisms, reducing oxidative stress, alleviating hypoxia, and facilitating glucose oxidation. The MoS @Au@BSA nanozyme-anchored injectable hydrogel, composed of oxidized dextran and glycol chitosan crosslinked through a Schiff base, significantly accelerates diabetic wound healing.

摘要

由于存在细菌感染、缺氧、高葡萄糖水平和氧化应激的风险,糖尿病伤口愈合仍然具有挑战性。葡萄糖激活级联反应可以消耗葡萄糖并消灭细菌,避免直接使用过氧化氢 (H2O2) 和对过氧化物酶样活性的伤口 pH 限制。然而,糖尿病伤口中的缺氧微环境会阻碍级联反应,因为葡萄糖氧化需要氧气 (O2)。在此,设计并将富含缺陷的二硫化钼纳米片负载牛血清白蛋白修饰的金纳米粒子 (MoS@Au@BSA NSs) 杂化物锚定到可注射水凝胶上,通过 O 自供应级联反应促进糖尿病伤口愈合。BSA 修饰降低了 Au 的粒径,提高了多种酶的活性。过氧化物酶样 Au 催化葡萄糖氧化成葡萄糖酸和 H2O2,H2O2 被过氧化物酶样 MoS@Au@BSA 转化为羟基自由基 (•OH) 以消灭细菌。当伤口 pH 值达到碱性条件时,MoS@Au@BSA 模拟超氧化物歧化酶将超氧阴离子转化为 O2 和 H2O2,并通过类似过氧化氢酶的机制将内源性和外源性 H2O2 分解为 O2,从而减轻氧化应激、缓解缺氧并促进葡萄糖氧化。由氧化葡聚糖和通过席夫碱交联的乙二醇壳聚糖组成的 MoS@Au@BSA 纳米酶锚定的可注射水凝胶显著加速糖尿病伤口愈合。

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