Metallacage-based enhanced PDT strategy for bacterial elimination via inhibiting endogenous NO production

Author:

Huang Kai1,Wang Jinbing2,Zhuang Ai3,Liu Qian4,Li Fupeng1,Yuan Kai1ORCID,Yang Yiqi1,Liu Yihao1ORCID,Chang Haishuang5,Liang Yakun5,Sun Yan6,Yan Xuzhou7ORCID,Tang Tingting1,Stang Peter J.6ORCID,Yang Shengbing1

Affiliation:

1. 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

2. 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

3. Department of Ophthalmology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China

4. Department of Laboratory Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China

5. Shanghai Institute of Precision Medicine, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China

6. Department of Chemistry, University of Utah, Salt Lake City, UT 84112

7. School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Key Laboratory of Electrical Insulation and Thermal Aging, Shanghai Jiao Tong University, Shanghai, 200240, China

Abstract

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.

Funder

MOST | National Natural Science Foundation of China

Shanghai Science and Technology Development Fund

Shanghai Sailing Program

the Interdisciplinary Program of Shanghai JiaoTong University

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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