Engineered Bacteria Labeled with Iridium(III) Photosensitizers for Enhanced Photodynamic Immunotherapy of Solid Tumors
Wenkai Lin
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
These authors contributed equally to this work.
Search for more papers by this authorYu Liu
National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027 China
These authors contributed equally to this work.
Search for more papers by this authorJinhui Wang
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorZhennan Zhao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorKai Lu
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorHe Meng
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorRuiqi Luoliu
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorXiaojun He
National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027 China
Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325001 China
Search for more papers by this authorCorresponding Author
Jianliang Shen
National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027 China
Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325001 China
Search for more papers by this authorCorresponding Author
Zong-Wan Mao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorCorresponding Author
Wei Xia
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorWenkai Lin
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
These authors contributed equally to this work.
Search for more papers by this authorYu Liu
National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027 China
These authors contributed equally to this work.
Search for more papers by this authorJinhui Wang
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorZhennan Zhao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorKai Lu
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorHe Meng
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorRuiqi Luoliu
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorXiaojun He
National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027 China
Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325001 China
Search for more papers by this authorCorresponding Author
Jianliang Shen
National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027 China
Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325001 China
Search for more papers by this authorCorresponding Author
Zong-Wan Mao
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorCorresponding Author
Wei Xia
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275 China
Search for more papers by this authorGraphical Abstract
An iridium (III) photosensitizer-bacteria hybrid (Ir-HEcN) targets the solid tumors and produces reactive oxygen species in situ upon photoirradiation, which induces pyroptosis of tumor cells and spontaneous self-elimination of Ir-HEcN. The resulting debris further evokes innate and adaptive anti-tumor immune responses. Therefore, Ir-HEcN-mediated treatment remarkably eradicates solid tumors via enhanced photodynamic immunotherapy.
Abstract
Despite metal-based photosensitizers showing great potential in photodynamic therapy for tumor treatment, the application of the photosensitizers is intrinsically limited by their poor cancer-targeting properties. Herein, we reported a metal-based photosensitizer-bacteria hybrid, Ir-HEcN, via covalent labeling of an iridium(III) photosensitizer to the surface of genetically engineered bacteria. Due to its intrinsic self-propelled motility and hypoxia tropism, Ir-HEcN selectively targets and penetrates deeply into tumor tissues. Importantly, Ir-HEcN is capable of inducing pyroptosis and immunogenic cell death of tumor cells under irradiation, thereby remarkably evoking anti-tumor innate and adaptive immune responses in vivo and leading to the regression of solid tumors via combinational photodynamic therapy and immunotherapy. To the best of our knowledge, Ir-HEcN is the first metal complex decorated bacteria for enhanced photodynamic immunotherapy.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
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