Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Orthopaedic Implants, Shanghai 200011, China.
Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Center for Oral Disease, Shanghai 200011, China.
Proc Natl Acad Sci U S A. 2023 Jul 18;120(29):e2218973120. doi: 10.1073/pnas.2218973120. Epub 2023 Jul 10.
Antibiotics are among the most used weapons in fighting microbial infections and have greatly improved the quality of human life. However, bacteria can eventually evolve to exhibit antibiotic resistance to almost all prescribed antibiotic drugs. Photodynamic therapy (PDT) develops little antibiotic resistance and has become a promising strategy in fighting bacterial infection. To augment the killing effect of PDT, the conventional strategy is introducing excess ROS in various ways, such as applying high light doses, high photosensitizer concentrations, and exogenous oxygen. In this study, we report a metallacage-based PDT strategy that minimizes the use of ROS by jointly using gallium-metal organic framework rods to inhibit the production of bacterial endogenous NO, amplify ROS stress, and enhance the killing effect. The augmented bactericidal effect was demonstrated both in vitro and in vivo. This proposed enhanced PDT strategy will provide a new option for bacterial ablation.
抗生素是对抗微生物感染最常用的武器之一，极大地提高了人类的生活质量。然而，细菌最终可能会进化到对几乎所有规定的抗生素药物都产生抗药性。光动力疗法（PDT）产生的抗生素耐药性很小，已成为对抗细菌感染的一种有前途的策略。为了增强 PDT 的杀伤效果，常规策略是通过各种方式引入过量的 ROS，例如应用高剂量的光、高浓度的光敏剂和外源性氧气。在这项研究中，我们报告了一种基于金属笼的 PDT 策略，该策略通过联合使用镓金属有机骨架棒来抑制细菌内源性 NO 的产生、放大 ROS 应激，从而最小化 ROS 的使用，增强杀伤效果。在体外和体内都证明了增强的杀菌效果。这种增强的 PDT 策略将为细菌消融提供新的选择。
