工程菌以铱(III)光敏剂标记,用于增强固体肿瘤的光动力免疫治疗。
Engineered Bacteria Labeled with Iridium(III) Photosensitizers for Enhanced Photodynamic Immunotherapy of Solid Tumors.
发表日期:2023 Sep 05
作者:
Wenkai Lin, Yu Liu, Jinhui Wang, Zhennan Zhao, Kai Lu, He Meng, Ruiqi Luoliu, Xiaojun He, Jianliang Shen, Zong-Wan Mao, Wei Xia
来源:
Cell Death & Disease
摘要:
尽管基于金属的光敏剂在肿瘤治疗的光动力疗法中显示出巨大潜力,但其应用因其对癌细胞的瞄准性能差而受到固有限制。在此,我们报道了一种金属基光敏剂和细菌的混合体,Ir-HEcN,通过将铱(III)光敏剂通过共价标记结合到基因工程菌表面。由于其固有的自运动机能和缺氧向性,Ir-HEcN可以选择性地瞄准和深入肿瘤组织。重要的是,Ir-HEcN能够在照射下诱导肿瘤细胞产生火焰状细胞死亡和免疫原性细胞死亡,从而在体内显著引发抗肿瘤的先天性和适应性免疫反应,并通过光动力免疫疗法的联合治疗导致实体肿瘤的退缩。据我们所知,Ir-HEcN是第一个用于增强光动力免疫疗法的金属配合物装饰细菌。© 2023 Wiley-VCH GmbH.
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.© 2023 Wiley-VCH GmbH.