Se-sensitized NIR hot band absorption photosensitizer for anti-Stokes excitation deep photodynamic therapy

Conventional anti-Stokes materials-involved deep photodynamic therapy (dPDT) requires much high-intensity irradiance due to low photosensitization efficiency. Herein, we proposed a “booster effector” approach to construct highly efficient hot band absorption phototherapeutics for low/biosafety power anti-Stokes light-triggered dPDT. Se, as “booster effector”, was introduced into hot band absorption luminophores (HBAs), which not only significantly facilitated intersystem crossing, but also simultaneously enhanced hot band excitation efficiency at v808, as a result successfully enabling excellent photogenerated singlet oxygen capability of HBAs under ultra-low power anti-Stokes excitation (10 mW cm−2in vitro). As far as we know, such low laser power-initiated photosensitization activity has never been reported in the existing anti-Stokes material systems. Importantly, FUC-SeME can self-assemble into uniform nanospheres in water, greatly boosting cellular uptake (>25-fold larger than FUC-Se), and achieve superior cancer-killing effect (808 nm, 10 mW cm−2, 5 min, the half-maximal inhibitory concentration IC50 = 1.36 µM). After further PEGylation with folate-attached polymer, the resultant FUC-SeME@FA can effectively enrich at the tumor (signal-to-background ratio, 10). Under safety irradiation (330 mW cm−2), FUC-SeME@FA effectively inhibits deep-seated tumor progression (the tumor growth inhibition rate, 84%). This work provides a successful paradigm, possibly being more clinically beneficial than conventional anti-Stokes materials.