Exploration of Thermally Activated Delayed Fluorescence (TADF)-Based Photoredox Catalyst To Establish the Mechanisms of Action for Photodynamic Therapy.

The mechanisms of action (MoA) have been proposed to further reduce the O 2 dependence of photodynamic therapy (PDT) significantly. However, the triplet states of traditional photosensitizers are relatively short and also are easily deactivated by the quenching of H 2 O or O 2 . This is not conducive for the electron transfer in the photocatalytic process and poses a great obstacle to establish the MoA. Therefore, we selected and synthesized a zirconium(IV) complex (Zr( Mes PDP Ph ) 2 ) reported by Milsmann to address this issue. The specific symmetric and intact geometry endowed Zr( Mes PDP Ph ) 2 NPs with long-lived triplet excited state (τ = 350 μs), desired sensitized ability, and improved anti-interfering performance on O 2 , which was matched with the requirements of photoredox catalyst significantly. The results showed that while PDT (I) and PDT (II) could be achieved simultaneously by leveraging Zr( Mes PDP Ph ) 2 NPs, it also could be served as a rare example of thermally activated delayed fluorescence (TADF)-based photoredox catalyst to implement the MoA of PDT. It involved the oxidation of NADH and the establishment of catalytic cycle collaborating by O 2 and cytochrome c (cyt c ) in normoxia and hypoxia, respectively. As a result, the oxygen-free PDT and tumor-growth inhibition was realized.