Indolizine-benzophenone hybrid acceptors enable TADF materials for bioimaging and photodynamic therapy in living cells

Thermally activated delayed fluorescence (TADF) emitters show great potential in photodynamic therapy (PDT) and bioimaging, leveraging their structural adaptability, efficient reverse intersystem crossing (RISC), robust photosensitizing capability, and high photoluminescence quantum yields (PLQYs). Herein, we developed a new class of donor–acceptor–donor (D-A-D)-type TADF materials by connecting the highly twisted indolizine-benzophenone electron acceptors with a series of electron donors including phenoxazine, phenothiazine and 9,9-dimethyl-9,10-dihydroacridine. These materials exhibit enhanced TADF properties, aggregation-induced emission (AIE), alongside high reactive oxygen species (ROS) generation efficiency, effectively mitigating aggregation-caused quenching observed in traditional fluorophores. Among them, IDP-p-PXZ, incorporating the phenoxazine donor, stands out with the smallest singlet–triplet splitting energy ( ΔE ST ) and the highest spin-orbit coupling matrix elements (SOCMEs). Upon encapsulation into 1,2-distearoyl- sn ‑glycero-3-phosphoethanolamine- N -[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) nanoparticles (NPs), IDP- p -PXZ demonstrates extended delayed fluorescence lifetimes in air, an exceptionally fast intersystem crossing (ISC) rate constant ( k ISC ) of 3.4 × 10 7 s −1 , and a radiative rate constant ( k r ) of 5.05 × 10 6 s −1 . These NPs exhibit superior biocompatibility, efficient cellular internalization, and potent ROS production, enabling effective simultaneous PDT and confocal fluorescence imaging in HeLa cells. In this work, indolizine-benzophenone was established as a potent molecular platform for AIE-active TADF emitters. Upon nanoparticle (NP) encapsulation, IDP-p-PXZ NPs exhibit superior biocompatibility, efficient cellular internalization, and potent ROS production, enabling effective simultaneous PDT and confocal fluorescence imaging in HeLa cells.