NIR-activated phase-transition thermal-propagation nanosystem for precision photothermal eradication of malignant melanoma

Multidrug resistance and the acidic tumor microenvironment (TME) of malignant melanoma significantly limit the efficacy of conventional therapies. In this study, we constructed a near-infrared (NIR)-responsive thermosensitive phase-transition core–shell nanosystem (CaO-DOX-IR820@DLTP). This nanosystem uses CaO as the core, co-loading the chemotherapeutic drug doxorubicin (DOX) and the photothermal agent IR820, with a thermosensitive DLTP polymer shell as the outer layer. Characterization results show that the nanosystem has a uniform particle size, good stability, and excellent biocompatibility. Under NIR irradiation, the hyperthermia generated by IR820 induces phase transition and melting of the DLTP shell, enabling controlled release of DOX. Meanwhile, CaO reacts with water in the TME to trigger a chain exothermic reaction, enhancing photothermal therapeutic efficacy. The resulting Ca (OH)₂ effectively neutralizes lactic acid in the TME, thereby inhibiting M2 polarization of tumor-associated macrophages (TAMs) and alleviating lactate-mediated immunosuppression. Both in vitro and in vivo experimental results demonstrate that the nanosystem exhibits favorable tumor cell-killing effects, providing a novel strategy for the treatment of malignant melanoma.