Hypoxia-triggered photothermal/drug combination therapy of tumors using a perylene diimide molecular capsule  

作　　者：Fei Yang Guo Wang Kecheng Huang Yanqing Xu Xiao Feng Weizhi Wang Wei Wei 

机构地区：[1]Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering,Ministry of Industry and Information Technology,School of Chemistry and Chemical Engineering,Beijing Institute of Technology,Beijing 100081,China [2]Beijing Key Laboratory for Optical Materials and Photonic Devices,Department of Chemistry,Capital Normal University,Beijing 100048,China

出　　处：《Science China Chemistry》2025年第3期1009-1017,共9页中国科学(化学英文版)

基　　金：supported by the National Natural Science Foundation of China (22171021 and 22322403);the Beijing Natural Science Foundation (2232027 and 2242004);the China Postdoctoral Science Foundation (2023M730245)。

摘　　要：Hypoxia is a common characteristic of tumors and associated with poor outcome in most cancer types,thus hypoxia-triggered combined therapeutic systems with well-defined structure hold significant promise for achieving specific and effective tumor destruction.Herein,a water-soluble perylene diimide(PDI)cyclophane“Gemini Box”(GBox-1^(4+))is demonstrated as both a hypoxia-responsive photothermal agent and a drug capsule for tumor-specific combination therapy.First,owing to the covalent enclosure of PDI chromophore by double-sided molecular straps,GBox-1^(4+)can significantly stabilize labile PDI radical anions generated through bioreduction at the lesion site of hypoxic tumors,leading to high-efficiency near-infrared photothermal ablation of tumors.Meanwhile,GBox-1^(4+)can act as a molecular capsule to bind water-insoluble antitumor drugs camptothecin and hydroxycamptothecin in 1:1 host-guest stoichiometry with high affinities,greatly enhancing the water solubility of drugs.Eventually,such drug-loading cyclophane system as a hypoxia-activated photothermal/drug combined therapeutic platform exhibits more effective inhibition of tumor growth than the single treatment under identical conditions.This study significantly extends the application range of host-guest cyclophane systems and opens a promising avenue to structurally uniform combined therapeutic agents against hypoxic tumors with improved specificity.

关 键 词：hypoxia-responsive photothermal agent CYCLOPHANES host-guest system NEAR-INFRARED combination therapy 

分 类 号：R730.5[医药卫生—肿瘤] TQ460.1[医药卫生—临床医学]