Photo-Facilitated Nitric Oxide-Triggered Turn-on Photodynamic Therapy for Precise Antitumor Application

• Published in: Advanced healthcare materials 2025-01, p.e2404265
• Main Authors: Qin, Yiliang, Gao, Hanyi, Yin, Yuting, Li, Jiayi, He, Xia, Gao, Meng, Sun, Liying, Yuan, Yi, Tian, Ying, Zhou, Yizhao, Zeng, Zebing, Zhang, Xiaodong, Hu, Rong
• Format: Article
• Language: English
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.202404265

Photodynamic therapy (PDT) is a powerful strategy for tumor therapy with noninvasiveness and desirable efficacy. However, the phototoxicity of photosensitizer after the post-PDT is the major obstacle limiting the clinic applications. Herein, a nitric oxide (NO)-activatable photosensitizer is reported with turn-on PDT behavior and endoplasmic reticulum (ER) targeting ability for precise tumor therapy. Four o-thiophenediamine derivatives with reaction-tunable donor/acceptor push-pull electronic effect are established, and the systematic structure and property relationship observation reveals the following features: 1) the reactivity against NO can be improved by enhancing the electron density and further facilitated upon photo-irradiation. 2) the reactivity with NO enables the improved intramolecular charge transfer process with the evoking of photosensitizing effect. 3) only o-thiophenediamine derivative with ER enrichment behavior exhibited cancer cell ablation effect compared to photosensitizers localized in lysosome and lipid droplet. Thus, the efficient inhibition of cancer cells both in vitro and in vivo is realized based on the photo-controlled PDT strategy. This work provides more insights into developing promising activatable photosensitizers for advanced therapy based on tumor microenvironment trigger.