Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital & Center for Molecular Imaging Probe & Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China; NHC Key Laboratory of Birth Defect Research and Prevention, MOE Key Lab of Rare Pediatric Disease & Institute of Cytology and Genetics, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital & Center for Molecular Imaging Probe & Hunan Engineering Research Center for Early Diagnosis and Treatment of Liver Cancer, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Int J Biol Macromol. 2024 Oct;277(Pt 4):134518. doi: 10.1016/j.ijbiomac.2024.134518. Epub 2024 Aug 5.
Bacterial biofilm-related infections have become a significant global concern in public health and economy. Extracellular DNA (eDNA) is regarded as one of the key elements of extracellular polymeric substances (EPS) in bacterial biofilm, providing robust support to maintain the stability of bacterial biofilms for fighting against environmental stresses (such as antibiotics, reactive oxygen species (ROS), and hyperthermia). In this study, ternary AuAgCu hydrogels nanozyme with porous network structures were utilized for the immobilization of DNase (AuAgCu@DNase hydrogels) to realize enhanced biofilm decomposition and antibacterial therapy of MRSA. The prepared AuAgCu@DNase hydrogels can efficiently hydrolyze eDNA in biofilms so that the generated ROS and hyperthermia by laser irradiation can permeate into the interior of the biofilm to achieve deep sterilization. The typical interface interactions between AuAgCu hydrogels and DNase and the excellent photothermal-boost peroxidase-like performances of AuAgCu hydrogels take responsibility for the enhanced antibacterial activity. In the MRSA-infected wounds model, the in vivo antibacterial results revealed that the AuAgCu@DNase hydrogels possess excellent drug-resistant bacteria-killing performance with superb biocompatibility. Meanwhile, the pathological analysis of collagen deposition and fibroblast proliferation of wounds demonstrate highly satisfactory wound healing. This work offers an innovative path for developing nanozyme-enzyme antibacterial composites against drug-resistant bacteria and their biofilms.
细菌生物膜相关感染已成为公共卫生和经济领域的重大全球关注问题。细胞外 DNA（eDNA）被认为是细菌生物膜中细胞外聚合物质（EPS）的关键要素之一，为维持细菌生物膜的稳定性提供了有力支持，以抵抗环境压力（如抗生素、活性氧（ROS）和高热）。在这项研究中，利用具有多孔网络结构的三元 AuAgCu 水凝胶纳米酶来固定 DNase（AuAgCu@DNase 水凝胶），以实现耐甲氧西林金黄色葡萄球菌（MRSA）生物膜的增强分解和抗菌治疗。所制备的 AuAgCu@DNase 水凝胶可以有效地水解生物膜中的 eDNA，从而使激光照射产生的 ROS 和高热能够渗透到生物膜内部，实现深层杀菌。AuAgCu 水凝胶与 DNase 之间的典型界面相互作用以及 AuAgCu 水凝胶优异的光热增强过氧化物酶样性能负责增强抗菌活性。在 MRSA 感染的伤口模型中，体内抗菌结果表明，AuAgCu@DNase 水凝胶具有出色的耐细菌杀伤性能和良好的生物相容性。同时，伤口胶原沉积和成纤维细胞增殖的病理分析表明，伤口愈合情况非常令人满意。这项工作为开发针对耐药细菌及其生物膜的纳米酶-酶抗菌复合材料提供了一条创新途径。
