Microtubule polymerization induced by iridium‐fullerene photosensitizers for cancer immunotherapy via dual‐reactive oxygen species regulation strategy
Xiaoxiao Chen, Kun Peng, Xi Chen, Zhengyin Pan, Qing‐Hua Shen, Yu‐Yi Ling, Jianzhang Zhao, Cai‐Ping Tan
Abstract
Abstract Microtubules (MTs) are key players in cell division, migration, and signaling, and they are regarded as important targets for cancer treatment. In this work, two fullerene (C 60 )‐functionalized Ir(III) complexes ( Ir‐C 60 1 and Ir‐C 60 2 ) are rationally designed as dual reactive oxygen species (ROS) regulators and MT‐targeted Type I/II photosensitizers. In the dark, Ir‐C 60 1 and Ir ‐C 60 2 serve as ROS scavengers to eliminate O 2 • − and •OH, consequently reducing the dark cytotoxicity and reversing dysfunctional T cells. Due to the efficiently populated C 60 ‐localized intraligand triplet state, Ir‐C 60 1 and I r ‐C 60 2 can be excited by green light (525 nm) to produce O 2 • − and •OONO − (Type I) and 1 O 2 (Type II) to overcome tumor hypoxia. Moreover, Ir‐C 60 1 is also able to photooxidize tubulin, consequently interfering with the cellular cytoskeleton structures, inducing immunogenic cell death and inhibiting cell proliferation and migration. Finally, Ir‐C 60 1 exhibits promising photo‐immunotherapeutic effects both in vitro and in vivo. In all, we report here the first MT stabilizing photosensitizer performing through Type I/II photodynamic therapy pathways, which provides insights into the rational design of new photo‐immunotherapeutic agents targeting specific biomolecules.