Heavy-atom engineered hypoxia-responsive probes for precisive photoacoustic imaging and cancer therapy

作     者：Ling-Ling Wu Xiangchuan Meng Qingyang Zhang Xiaowan Han Feiya Yang Qinghua Wang Hai-Yu Hu Nianzeng Xing Ling-Ling Wu;Xiangchuan Meng;Qingyang Zhang;Xiaowan Han;Feiya Yang;Qinghua Wang;Hai-Yu Hu;Nianzeng Xing

作者机构：Department of UrologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Bioactive Substances and Function of Natural MedicineInstitute of Materia MedicaPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100050China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2024年第35卷第4期

页      面：316-320页

核心收录：

学科分类：1002[医学-临床医学] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070302[理学-分析化学] 0703[理学-化学] 100214[医学-肿瘤学] 10[医学] 

基　　金：partially supported by the National Key R&D Program of China (No.2022YFE0199700) the National Natural Science Foundation of China (NSFC) projects (Nos.22077139and 22122705) CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2022-I2M-2–002) 

主　　题：Heavy-atom effect Phototherapy Photoacoustic imaging Hypoxia-responsive Prostate cancer 

摘      要：Photoacoustic agents combining photodynamic therapy(PDT) and photothermal therapy(PTT) functions have emerged as potent theranostic agents for combating cancer. The molecular approaches for enhancing the near-infrared(NIR)-absorption and maximizing non-radiative energy transfer are essential for effective photoacoustic imaging(PAI) and therapy applications. In addition, such molecules with high specificity and affinity to cancer cells are urgently needed, which would further decrease the side effect during treatments. In this study, we applied a heavy-atom engineering strategy and introduced p-aminophenol,-thio, and-seleno moieties into NIR heptamethine cyanine(Cy7) skeleton(Cy7-X-NH_(2), X = O, S, Se) to significantly increase photothermal conversion efficiency for PTT and promote intersystem crossing for ***, we designed a series of nitroreductase(NTR)-activated photoacoustic probes(Cy7-X-NO_(2),X = O, S, Se), and target hypoxic tumors with NTR overexpression. Our prostate cancer targeting probe,Cy7-Se-NO_(2)-KUE, exhibited specific tumor photoacoustic signals and effective tumor killing through outstanding synergistic PTT/PDT in vivo. These findings highlighted a versatile strategy for cancer photoacoustic diagnosis and enhanced phototherapy.