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 is 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 MnO 2 nanoparticles (MnO 2 @BSA) by directly reducing KMnO 4 with BSA, which were then combined with naringenin to achieve immuno-enhanced PTT for TNBC. The results show that MnO 2 @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. In vivo 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.