State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha 410081, China.
Central Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academic of Medical Sciences & Peking Union Medical College, Shenzhen 518116, China.
J Mater Chem B. 2022 Oct 5;10(38):7744-7759. doi: 10.1039/d2tb01200f.
Multimodal synergistic bactericidal agents display great potential for fighting biofilm infections. However, the rational design of biofilm microenvironment (BME)-activatable therapeutic agents with excellent specificities, effective eradications and minimal side effects remains a great challenge. Herein, we show a BME-responsive one-for-all bactericidal nanoplatform consisting of Fe-doped polydopamine (Fe/PDA)-capped ZnO nanoparticles with a successive assembly of methylene blue (MB) and poly(ethylene glycol) (PEG). In an acidic BME (pH 5.5), the constructed nanoagent (ZnPMp) can realize the co-delivery of dual metal ions (Zn and Fe) and MB, and the latter shows an activated photodynamic antibacterial activity when irradiated with 635 nm laser. Zn produced from acid-sensitive dissolution of ZnO is an effective chemical antibacterial agent. Additionally, the released Fe is reduced to Fe by glutathione (GSH) overexpressed in the BME to generate Fe/Fe redox couples, which exhibit Fenton catalytic activity to convert endogenous HO to hydroxyl radicals (˙OH) for chemodynamic sterilization and GSH depletion ability to improve ˙OH-induced oxidative damage. Interestingly, the hyperthermia caused by the Fe/PDA layer assisted with 808 nm laser can damage directly bacterial cells, accelerate the release of Zn, Feand MB, and promote the catalytic activity of Fe/Fe redox couples for photothermal-augmented multimodal antibiofilm therapy. With the help of dual lasers, ZnPMp displays the broad-spectrum antibacterial effect, inhibits effectively the formation of biofilms, and more importantly eliminates bacteria deep in mature biofilms. In addition, ZnPMp can be used to treat biofilm-related infections with excellent therapeutic performance and minimal toxicity. Overall, the developed ZnPMp may serve as a potential nano-antibacterial agent for intensive anti-infective therapy.
多模态协同杀菌剂在对抗生物膜感染方面具有巨大的潜力。然而，合理设计具有优异特异性、有效根除和最小副作用的生物膜微环境 (BME) 激活治疗剂仍然是一个巨大的挑战。在此，我们展示了一种由掺杂铁的聚多巴胺 (Fe/PDA) 包裹的 ZnO 纳米粒子组成的 BME 响应型全杀型杀菌纳米平台，其具有亚甲蓝 (MB) 和聚乙二醇 (PEG) 的连续组装。在酸性 BME (pH 5.5) 中，构建的纳米制剂 (ZnPMp) 可以实现双金属离子 (Zn 和 Fe) 和 MB 的共递送，当用 635nm 激光照射时，后者表现出激活的光动力抗菌活性。由 ZnO 的酸敏溶解产生的 Zn 是一种有效的化学抗菌剂。此外，在 BME 中过表达的谷胱甘肽 (GSH) 将释放的 Fe 还原为 Fe，生成 Fe/Fe 氧化还原对，其表现出芬顿催化活性，将内源性 HO 转化为羟基自由基 (˙OH) 进行化学动力学杀菌，并具有 GSH 耗竭能力，以增强 ˙OH 诱导的氧化损伤。有趣的是，由 Fe/PDA 层辅助 808nm 激光产生的热疗可以直接损伤细菌细胞，加速 Zn、Fe 和 MB 的释放，并促进 Fe/Fe 氧化还原对的催化活性，用于光热增强多模态抗生物膜治疗。在双激光的帮助下，ZnPMp 表现出广谱抗菌作用，有效抑制生物膜的形成，更重要的是可以消除成熟生物膜中的深层细菌。此外，ZnPMp 可用于治疗生物膜相关感染，具有优异的治疗效果和最小的毒性。总的来说，所开发的 ZnPMp 可能成为一种用于强化抗感染治疗的潜在纳米抗菌剂。
