Time-resolved image-guided Type-I photosensitization using a delayed fluorescent emitter

The development of next-generation image-guided thermally activated delayed fluorescent photosensitizers requires high quantum yield, organelle specificity, and low oxygen dependence to enable effective photodynamic therapy. A subtle balance between the opposing requirements of strong radiative transition for high-contrast imaging and efficient nonradiative decay for reactive oxygen species generation remains a key challenge for time-resolved image-guided photodynamic therapy. In this study, we present a lipid droplet (LD) targeting delayed fluorescent probe, based on substituted keto-coumarin, DCBP, and its water-dispersible nanoparticles. DCBP in solution and aqueous dispersions exhibits long-lived emission and possesses an optimum excited-state oxidation potential, promising for time-resolved image-guided Type-I photosensitization. The intrinsic hydrophobicity of DCBP nanoparticles promotes specificity towards lipid droplets, exhibiting pronounced phototoxicity under normoxic and hypoxic conditions via dual-mode photosensitization through superoxide anion radical generation and NADH oxidation. Furthermore, polymer-encapsulated DCBP nanoparticles (DP-NPs) enable time-resolved luminescence imaging of lipid-rich fat bodies in Drosophila larvae at the microsecond scale, followed by effective image-guided photosensitization. This work creates exciting yet underexplored avenues for time-resolved imaging using Type-I delayed fluorescent photosensitizers for targeted intracellular image-guided photodynamic therapy.