Microtubule polymerization induced by iridium-fullerene photosensitizers for cancer immunotherapy via dual-reactive oxygen species regulation strategy  

作　　者：Xiao-Xiao Chen Kun Peng Xi Chen Zheng-Yin Pan Qing-Hua Shen Yu-Yi Ling Jian-Zhang Zhao Cai-Ping Tan 

机构地区：[1]MOE Key Laboratory of Bioinorganic and Synthetic Chemistry,School of Chemistry,Sun Yat-Sen University,Guangzhou,P.R.China [2]Guangdong Basic Research Center of Excellence for Functional Molecular Engineering,Sun Yat-Sen University,Guangzhou,P.R.China [3]State Key Laboratory of Fine Chemicals,Frontiers Science Center for Smart Materials,School of Chemical Engineering,Dalian University of Technology,Dalian,P.R.China

出　　处：《Aggregate》2024年第6期272-283,共12页聚集体(英文)

基　　金：National Natural Science Foundation of China,Grant/Award Number:22177142;Basic and Applied Basic Research Foundation of Guangdong Province,Grant/Award Numbers:2022A1515111089,2023A1515010625,2024B1515040028。

摘　　要：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 Ir-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.

关 键 词：ANTICANCER FULLERENE iridium complexes MICROTUBULE photo-immunotherapy 

分 类 号：R73[医药卫生—肿瘤]