Electron-donor planar extension based on donor-acceptor-donor molecules generates charge transfer-mediated J-aggregates for NIR-II photothermal immunotherapy and bacterial elimination.

Second near-infrared photothermal therapy (NIR-II-PTT) has emerged as a promising therapeutic modality in diverse medical aspects. In particular, J-aggregate is a potential strategy to develop high-performance NIR-II-PTT materials, however, it suffers from specific molecular skeletons and complex control conditions. Herein, we presented a simply electron-donor planar extension strategy to develop donor-acceptor-donor (D-A-D) type small molecules with charge-transfer (CT)-mediated J-aggregation for NIR-II PTT. By integrating ring-fused thiophene units in a benzo[1,2-'c:4,5-c']bis[1,2,5]thiadiazole (BBTDT) scaffold, we enabled tunable electrostatic and π-π interactions, promoting CT-mediated J-aggregate formation. The resulting BDTT nanoparticles showed an impressive light-harvesting capability (ɛ1064) of 2.92 × 104 M-1 cm-1 under 1064 nm excitation, yielding an exceptional photothermal performance (ɛ1064 × PCE = 1.99 × 104), which surpasses those of reported D-A-D type NIR-II-absorbing small molecules. This outstanding NIR-II photothermal property induced sufficient immunogenic cell death and amplified the final ablation of deep-seated tumor in conjunction with programmed cell death protein 1 (PD-1). Meanwhile, the fabricated BDTT nanoparticles also facilitated hyperthermia-triggered bacterial death. Together, this study provides valuable insights into developing NIR-II-absorbing J-aggregates based on D-A-D type small molecules, and offers critical potentials to treat malignant tumors and prevents postsurgical infections.