Regulating Triplet Energy Level and Intramolecular Motion: An Aggregation-Induced Emission BODIPY for Near-Infrared...

The combination of photodynamic therapy (PDT) and photothermal therapy (PTT) holds considerable promise for cancer treatment, but conventional Type II PDT is strongly limited by tumor hypoxia. Here, we designed a D-π-A-π-D BODIPY-based near-infrared aggregation-induced emission (AIE) photosensitizer, TBSN, by integrating tetraphenylethylene units and a rotatable N,N-diethylaniline moiety. Theoretical calculations identified S1 → T2 as the predominant intersystem crossing pathway and showed that the N,N-diethylaniline unit participated in the electronic redistribution of the T2 state. The calculated T1 → S0 energy of 0.42 eV made the energy-transfer process required for singlet-oxygen sensitization thermodynamically unfavorable. Electron paramagnetic resonance (EPR) spin-trapping experiments detected light-induced superoxide radical anions (O2·-) and hydroxyl radicals (·OH), but no discernible singlet oxygen (1O2) signal, supporting predominantly Type I reactive oxygen species (ROS) generation. Molecular dynamics simulations further showed that the molecular rotor retained considerable rotational freedom after aggregation, consistent with the photothermal conversion efficiency of 54.44%. After encapsulation with DSPE-PEG2000, TBSN@PEG retained pronounced ROS-generating and photothermal activities and exhibited effective photocytotoxicity under both normoxic and hypoxic conditions. Following intratumoral administration and 730 nm irradiation, TBSN@PEG produced localized heating and markedly inhibited 4T1 tumor growth, while showing favorable preliminary short-term biosafety at the tested dose. These results demonstrate a molecular design strategy that jointly regulates triplet-state electronic structure and residual rotor motion to balance Type I ROS generation and photothermal conversion.