肺癌是一种高度流行且致命的癌症，通常与氧化应激有关。光动力疗法（PDT）已成为癌症治疗中一种有前途的替代治疗工具，但其疗效与产生活性氧（ROS）的光敏剂和肿瘤细胞的抗氧化能力密切相关。特别是，谷胱甘肽 (GSH) 会减少 ROS，从而损害 PDT 疗效。在这项研究中，开发了一种基于聚集诱导发射的GSH响应性近红外光敏剂（TBPPN），用于实时监测GSH水平和增强PDT用于肺癌治疗。 TBPPN 的战略设计由供体-受体结构和二硝基苯的掺入组成，不仅可以通过 GSH 激活荧光，还可以消耗 GSH 以增强 PDT 的细胞毒性作用，从而实现双重功能。 TBPPN 通过特异性靶向不同的细胞区室并消耗细胞内 GSH，在体外展示了针对 A549 肺癌细胞的协同 PDT 功效。体内研究进一步证实TBBPN可以有效抑制肺癌小鼠模型中的肿瘤生长，凸显了其作为肺癌诊断和治疗综合药物的潜力。这种方法增强了 PDT 对肺癌的有效性，值得进一步探索其临床应用潜力。© 2024 Wiley‐VCH GmbH。

Lung cancer, a highly prevalent and lethal form of cancer, is often associated with oxidative stress. Photodynamic therapy (PDT) has emerged as a promising alternative therapeutic tool in cancer treatments, but its efficacy is closely correlated to the photosensitizers generating reactive oxygen species (ROS) and the antioxidant capacity of tumor cells. In particular, glutathione (GSH) can reduce the ROS and thus compromise PDT efficacy. In this study, a GSH-responsive near-infrared photosensitizer (TBPPN) based on aggregation-induced emission for real-time monitoring of GSH levels and enhanced PDT for lung cancer treatment is developed. The strategic design of TBPPN, consisting of a donor-acceptor structure and incorporation of dinitrobenzene, enables dual functionality by not only the fluorescence being activated by GSH but also depleting GSH to enhance the cytotoxic effect of PDT. TBPPN demonstrates synergistic PDT efficacy in vitro against A549 lung cancer cells by specifically targeting different cellular compartments and depleting intracellular GSH. In vivo studies further confirm that TBPPN can effectively inhibit tumor growth in a mouse model with lung cancer, highlighting its potential as an integrated agent for the diagnosis and treatment of lung cancer. This approach enhances the effectiveness of PDT for lung cancer and deserves further exploration of its potential for clinical application.© 2024 Wiley‐VCH GmbH.