Zuo Yunfei, Li Pei, Wang Wen-Jin, Xu Changhuo, Xu Shuting, Sung Herman H Y, Sun Jianwei, Jin Guorui, Wang Weiping, Kwok Ryan T K, Lam Jacky W Y, Tang Ben Zhong
Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, Division of Life Science, State Key Laboratory of Molecular Neuroscience, and Department of Chemical and Biological Engineering, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, 999077, P. R. China.
National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, 518112, China.
Adv Sci (Weinh). 2025 Jan;12(4):e2409506. doi: 10.1002/advs.202409506. Epub 2024 Nov 29.
Precise tumor diagnosis and treatment remain complex challenges. While numerous fluorescent probes have been developed for tumor-specific imaging and therapy, few exhibit effective function in vivo. Herein, a probe called TQ-H is designed that can realize robust theranostic effects both in vitro and in vivo. In vitro, TQ-H specifically targets the lysosome and reacts with hydroxyl radical (·OH) to generate TQ-HA, which lights up the cells. TQ-HA generates reactive oxygen species (ROS) under light irradiation, enabling the simultaneous induction and monitoring of apoptosis and ferroptosis in tumor cells. Remarkably, TQ-HA also acts as a self-amplifier, autocatalytically activating TQ-H by generating ·OH under light exposure. This self-amplification aligns with the tumor microenvironment, where TQ-H undergoes chemical transformation, distinguishing tumors from healthy tissue via near-infrared (NIR) fluorescence imaging. Furthermore, ROS generated by TQ-HA effectively kills tumor cells and inhibits tumor growth without harming normal cells. This study offers a promising strategy for targeted tumor theranostics using self-amplifying microenvironment-responsive fluorescent probes.
精确的肿瘤诊断和治疗仍然是复杂的挑战。虽然已经开发出许多用于肿瘤特异性成像和治疗的荧光探针，但很少有在体内表现出有效功能的。在此，设计了一种名为TQ-H的探针，它可以在体外和体内实现强大的诊疗效果。在体外，TQ-H特异性靶向溶酶体并与羟基自由基(·OH)反应生成TQ-HA，从而使细胞发光。TQ-HA在光照下产生活性氧(ROS)，能够同时诱导和监测肿瘤细胞中的细胞凋亡和铁死亡。值得注意的是，TQ-HA还充当自放大器，通过在光照下产生·OH来自动催化激活TQ-H。这种自放大与肿瘤微环境相匹配，在肿瘤微环境中TQ-H会发生化学转化，通过近红外(NIR)荧光成像将肿瘤与健康组织区分开来。此外，TQ-HA产生的ROS能有效杀死肿瘤细胞并抑制肿瘤生长，而不会损害正常细胞。这项研究为使用自放大微环境响应荧光探针进行靶向肿瘤诊疗提供了一种有前景的策略。
