Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, 410082, China.
Faculty of Science and Technology, University of Macau, Taipa, Macau, 999078, China.
Adv Sci (Weinh). 2022 Feb;9(6):e2104576. doi: 10.1002/advs.202104576. Epub 2022 Jan 6.
Increasing antibiotic resistance becomes a serious threat to public health. Photothermal therapy (PTT) and antibacterial enzyme-based therapy are promising nonresistant strategies for efficiently killing drug-resistant bacteria. However, the poor thermostability of enzymes in PTT hinders their synergistic therapy. Herein, antibacterial glucose oxidase (GOx) is embedded in a Ag graphitic nanocapsule (Ag@G) arrayed silk film to fabricate a GOx-synergistic PTT system (named silk-GOx-Ag@G, SGA). The SGA system can stabilize GOx by a vitrification process through the restriction of hydrogen bond and rigid β-sheet, and keep the antibacterial activity in the hyperthermal PTT environment. Moreover, the arrayed Ag@G possesses excellent chemical stability due to the protection of graphitic shell, providing stable plasmonic effect for integrating PTT and surface enhanced Raman scattering (SERS) analysis even in the GOx-produced H O environment. With in situ SERS identification of bacterial intrinsic signals in the mouse wound model, such SGA realizes superior synergistic antibacterial effect on the infected Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus in vivo, while without causing significant biotoxicity. This system provides a therapeutic method with low resistance and in situ diagnosis capability for efficiently eliminating bacteria.
抗生素耐药性的增加对公共卫生构成了严重威胁。光热疗法(PTT)和基于抗菌酶的疗法是一种有前途的非耐药策略,可以有效地杀死耐药细菌。然而,酶在 PTT 中的耐热性差阻碍了它们的协同治疗。在此,将抗菌葡萄糖氧化酶(GOx)嵌入到 Ag 石墨纳米胶囊(Ag@G)排列的丝膜中,以构建 GOx 协同 PTT 系统(命名为丝-GOx-Ag@G,SGA)。SGA 系统通过氢键和刚性β-折叠的限制,通过玻璃化过程稳定 GOx,并在过热的 PTT 环境中保持抗菌活性。此外,由于石墨壳的保护,排列的 Ag@G 具有优异的化学稳定性,为整合 PTT 和表面增强拉曼散射(SERS)分析提供了稳定的等离子体效应,即使在 GOx 产生的 H2O 环境中也是如此。通过在小鼠伤口模型中对细菌固有信号进行原位 SERS 鉴定,该 SGA 在体内对感染的大肠杆菌、金黄色葡萄球菌和耐甲氧西林金黄色葡萄球菌实现了优异的协同抗菌效果,而没有引起明显的生物毒性。该系统提供了一种具有低耐药性和原位诊断能力的治疗方法,可有效消除细菌。