Lin Wenkai, Liu Yu, Wang Jinhui, Zhao Zhennan, Lu Kai, Meng He, Luoliu Ruiqi, He Xiaojun, Shen Jianliang, Mao Zong-Wan, Xia Wei
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, IGCME, Sun Yat-Sen University, Guangzhou, 510275, China.
National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Angew Chem Int Ed Engl. 2023 Oct 23;62(43):e202310158. doi: 10.1002/anie.202310158. Epub 2023 Sep 14.
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.
尽管基于金属的光敏剂在肿瘤光动力治疗中显示出巨大潜力,但这些光敏剂的应用因其较差的癌症靶向特性而受到内在限制。在此,我们报道了一种基于金属的光敏剂-细菌杂交体Ir-HEcN,它是通过将铱(III)光敏剂共价标记到基因工程细菌表面而构建的。由于其固有的自推进运动性和缺氧趋向性,Ir-HEcN能选择性地靶向并深入渗透到肿瘤组织中。重要的是,Ir-HEcN在光照下能够诱导肿瘤细胞发生焦亡和免疫原性细胞死亡,从而在体内显著激发抗肿瘤固有免疫和适应性免疫反应,并通过联合光动力治疗和免疫治疗导致实体瘤消退。据我们所知,Ir-HEcN是第一种用于增强光动力免疫治疗的金属配合物修饰细菌。