Molecular Design of Monochromophore-Based Bifunctional Photosensitizers for Simultaneous Ratiometric Oxygen Reporting and Photodynamic Cancer Therapy

Monitoring the tumor oxygen level when implementing photodynamic therapy (PDT) on malignant cancer has vital significance but remains challenging yet. Herein, by structurally manipulating a 2,4-dimethylpyrrole-engineered asymmetric BODIPY scaffold with different kinds, numbers, and positions of halogen atoms, we rationally designed several monochromophore-based bifunctional photosensitizers, named BDPs ( BDP-I , BDP-II , and BDP-III ), with self-sensitized photooxidation characteristics for accurate oxygen reporting and photodynamic tumor ablation. We show that different ways of halogen regulation allow available tuning of BDPs ’ oxygen-dependent ratiometric fluorescence turn-ons upon light irradiation as well as type-II PDT efficiencies before and after self-sensitized photooxidation. Encouragingly, measuring the specific ratiometric signals of the most promising BDP-II enabled the direct observation of initial oxygen concentration in both living 4T1 cells and a tumor-bearing mice model, affording an alternative way for evaluating oxygen supplementation strategies. Meanwhile, the “always on” PDT effect of BDP-II ensured efficient tumor ablation via apoptosis. Our research was thus believed to be of instructive significance for future application of oxygen-related auxiliary strategies and the design of unimolecular multifunctional PDT agents for cancer precision therapy.