Potentiating light-harvesting tactics through an A–D–A structure: repolarization of tumor-associated macrophages through phototherapy

Aiming to decrease the recurrence of tumors and achieve patient satisfaction, the elicitation of immunotherapy and its integrated synergistic employment is a bright new direction in oncotherapy, yet an emergently challenging task. In particular, tumor-associated macrophage (TAM) regulation though light-induced photodynamic and photothermal therapy (PDT and PTT) is regarded as a powerful approach, which focuses on the systemic immune system instead of the tumor itself. Herein, this study reports an acceptor-donor-acceptor (A-D-A) aggregation-induced emission luminogen (AIEgen), named TPA-2CN, which was applied as a photosensitizer (PS) and photothermal agent (PTA). Attributed to its A-D-A structure and AIE properties, TPA-2CN exhibits a high molar absorption coefficient and acts as a perfect template in regulating radiative and nonradiative transitions, which mainly utilize excited energy. The generation of type I reactive oxygen promoted its application in hypoxic tumor sites and the combination of hyperpyrexia forcefully induces macrophages to polarize towards the immune response M1 phenotype. In