Synergistic immunomodulatory effects of naringenin and photothermal therapy in triple-negative breast cancer

Triple-negative breast cancer (TNBC) represents a highly aggressive subtype with limited treatment options, primarily relying on chemotherapy. Emerging therapies, including photothermal therapy (PTT) and related combination therapies, are considered highly promising. Naringenin, a flavonoid glycoside with diverse biological activities, can enhance immune responses as well as inhibit cancer cell proliferation. We developed photothermal bovine serum albumin (BSA)-biomineralized MnO₂ nanoparticles (MnO₂@BSA) by directly reducing KMnO₄ with BSA, which were then combined with naringenin to achieve immuno-enhanced PTT for TNBC. The results show that MnO₂@BSA exhibits strong light absorption and tumor-targeting capabilities. Naringenin and PTT together significantly suppress TNBC cell proliferation and migration while enhancing antitumor immune responses. <i>In vivo</i> experiments confirm that the combined therapy reduces tumor growth and metastatic risk compared to monotherapy. Additionally, the treatment exhibits a favorable safety profile, offering potential for improved clinical outcomes in breast cancer treatment.