Wang Hanjie, Guo Xinqi, Tan Ying, Yang Junxu, Ye Yuting, Mo Miao, Liang Yanling, Li Guanhua, Huang Zhangrui, Zheng Li, Ding Xiaofei, Zhong Jingping, Zhao Jinmin
Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Coconstructed By the Province and Ministry, Guangxi Key Laboratory of Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, PR China.
Life Sciences Institute, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, Guangxi, 530021, PR China.
Mater Today Bio. 2025 Jul 16;34:102097. doi: 10.1016/j.mtbio.2025.102097. eCollection 2025 Oct.
Bacterial and drug-resistant bacterial infections pose significant challenges to the treatment of skin wounds. Among various non-antibiotic strategies, nanozymes which mimic the activities of natural bioenzymes and possess broad-spectrum antibacterial properties, hold promise for antibacterial therapy in infected wounds. However, the catalytic activity and biosafety of most current nanozymes remain insufficient to meet clinical requirements. Herein, we innovatively synthesized novel heterostructured nanozymes (HNiZn) comprising NiN/NiZnC embedded in accordion-shaped nitrogen-doped carbon using a simple molten-salt pyrolysis method. Combined with injectable hyaluronic acid (HA) as a carrier, these nanozymes facilitate low-temperature (43.5 °C) photocatalytic and photothermal therapy for bacterially infected wounds. Based on density functional theory (DFT) calculations, the NiN/NiZnC. heterostructured nanozymes exhibit richer electron cloud distribution, stronger interactions between heterogeneous atoms, lower electron escape work function, stronger adsorption energy for free radicals, and electron transfer efficiency than individual NiN or NiZnC phases, resulting in efficient peroxidase (POD)-like and glutathione peroxidase (GPx)-like activities. Additionally, HNiZn exhibits a high photothermal conversion efficiency (51.01 %) under near infrared (NIR) irradiation. Through combined photocatalytic and photothermal effects, it effectively kills (), clinically isolated methicillin-resistant (MRSA), and their biofilms. Mechanistic studies using metabolomics analysis revealed that HNiZn induces bacterial apoptosis by disrupting bacterial biosynthesis and metabolism, affecting the cell cycle, and perturbing redox balance. In vivo experiments further confirmed the favorable biosafety and antibacterial efficacy of HNiZn, which promoted skin wound healing. This study provides a novel strategy for constructing effective nanozymes and treating bacterial infections.
细菌感染和耐药性细菌感染对皮肤伤口的治疗构成了重大挑战。在各种非抗生素策略中,纳米酶模仿天然生物酶的活性并具有广谱抗菌特性,有望用于感染伤口的抗菌治疗。然而,目前大多数纳米酶的催化活性和生物安全性仍不足以满足临床需求。在此,我们创新性地采用简单的熔盐热解法合成了新型异质结构纳米酶(HNiZn),其由嵌入手风琴状氮掺杂碳中的NiN/NiZnC组成。这些纳米酶与可注射的透明质酸(HA)作为载体相结合,有助于对细菌感染伤口进行低温(43.5°C)光催化和光热治疗。基于密度泛函理论(DFT)计算,与单个NiN或NiZnC相相比,NiN/NiZnC异质结构纳米酶表现出更丰富的电子云分布、更强的异质原子间相互作用、更低的电子逸出功函数、更强的自由基吸附能和电子转移效率,从而产生高效的类过氧化物酶(POD)和类谷胱甘肽过氧化物酶(GPx)活性。此外,HNiZn在近红外(NIR)照射下表现出高光热转换效率(51.01%)。通过光催化和光热效应的联合作用,它能有效杀灭临床分离的耐甲氧西林金黄色葡萄球菌(MRSA)及其生物膜。使用代谢组学分析的机制研究表明,HNiZn通过破坏细菌的生物合成和代谢、影响细胞周期以及扰乱氧化还原平衡来诱导细菌凋亡。体内实验进一步证实了HNiZn良好的生物安全性和抗菌效果,其促进了皮肤伤口愈合。本研究为构建有效的纳米酶和治疗细菌感染提供了一种新策略。