ABSTRACT Despite the therapeutic promise of photothermal immunotherapy in triple‐negative breast cancer (TNBC), engineering second near‐infrared (NIR‐II) window‐responsive organic immunophotothermal agents persists as a critical hurdle. We address this gap by designing a molecularly tailored NIR‐II photothermal sensitizer (BOQCyCN), which concurrently enables tumor‐localized hyperthermia and systemic immunomodulation for combinatorial tumor clearance. Rational structure manipulation through benzyl donor‐cyano acceptor functionalization on a 4‐methylquinoline core induces a redshifted absorption maximum (λ max = 1022 nm), achieving deep‐tissue penetration within the NIR‐II biological therapeutic window. Co‐assembly with DSPE‐mPEG2000 generates stable BOQCyCN nanoparticles (NPs) exhibiting ultrahigh photothermal conversion (PCE, η = 62.9%) and irradiation resistance. At low irradiance (1064 nm, 0.6 W cm − 2 ), NPs initiate synergistic therapeutic cascades: (1) Primary tumor ablation (95% volume reduction) with amplified T‐cell infiltration (CD8 + : 5.5‐fold; CD4 + : 2.3‐fold); (2) Immunophenotype reprogramming via pro‐inflammatory M1 macrophage skewing (M1/M2: 2.55 vs. 0.33); (3) Metastatic suppression (96% reduced distal tumor burden). This thermo‐immunological nanoplatform establishes crosstalk between localized hyperthermia and antitumor immunity, advancing a translatable paradigm for TNBC management.
Wang et al. (Thu,) studied this question.