School of Pharmacy, Henan University, Kaifeng 475004, China.
Department of Pharmacy, Shangqiu First People's Hospital, Shangqiu 476100, China.
J Mater Chem B. 2024 Jan 31;12(5):1317-1329. doi: 10.1039/d3tb02577b.
Bacterial biofilm infection is a serious obstacle to clinical therapeutics. Photodynamic therapy (PDT) plays a dynamic role in combating biofilm infection by utilizing reactive oxygen species (ROS)-induced bacterial oxidation injury, showing advantages of mild side effects, spatiotemporal controllability and little drug resistance. However, superfluous glutathione (GSH) present in biofilm and bacteria corporately reduces ROS levels and seriously affects PDT efficiency. Herein, we have constructed a Cu-infused porphyrin metal-organic framework (MOF@Cu) for the enhanced photodynamic combating of biofilm infection by the maximum depletion of GSH. Our results show that the released Cu from porphyrin MOF@Cu could not only oxidize GSH in biofilm but also consume GSH leaked from ROS-destroyed bacteria, thus greatly weakening the antioxidant system in biofilm and bacteria and dramatically improving the ROS levels. As expected, our dual-enhanced PDT nanoplatform exhibits a strong biofilm eradication ability both and in an biofilm-infected mouse model. In addition, Cu can promote biofilm-infected wound closing by provoking cell immigration, collagen sediment and angiogenesis. Besides, no apparent toxicity was detected after treatment with MOF@Cu. Overall, our design offers a new paradigm for photodynamic combating biofilm infection.
细菌生物膜感染是临床治疗的严重障碍。光动力疗法（PDT）通过利用活性氧（ROS）诱导的细菌氧化损伤在对抗生物膜感染方面发挥着重要作用，具有副作用轻微、时空可控性和耐药性小的优点。然而，生物膜和细菌中共存的过多谷胱甘肽（GSH）会降低 ROS 水平，严重影响 PDT 效率。在这里，我们构建了一种铜注入卟啉金属-有机骨架（MOF@Cu），通过最大限度地消耗 GSH 来增强光动力对抗生物膜感染。我们的结果表明，从卟啉 MOF@Cu 中释放的 Cu 不仅可以氧化生物膜中的 GSH，还可以消耗 ROS 破坏的细菌中泄漏的 GSH，从而大大削弱生物膜和细菌中的抗氧化系统，并显著提高 ROS 水平。正如预期的那样，我们的双重增强 PDT 纳米平台在 和 生物膜感染的小鼠模型中均表现出强大的生物膜清除能力。此外，Cu 可以通过引发细胞迁移、胶原蛋白沉淀和血管生成来促进生物膜感染伤口的闭合。此外，用 MOF@Cu 处理后未检测到明显的毒性。总的来说，我们的设计为光动力对抗生物膜感染提供了一种新的范例。
