Photothermal Nanomedicine-Mediated Modulation of Mitochondrial Oxidative Respiration in Breast Cancer

Mild photothermal therapy (PTT) has gained traction for minimizing thermal damage while enhancing tumor immunogenicity. However, hyperthermia (>5°C above body temperature) induces heat shock protein (HSP) overexpression through ATP-dependent mechanisms, with mitochondrial oxidative phosphorylation (OXPHOS) being a key ATP source in cancers. We developed biogenic magnetosomes with Fe 3 O 4 cores and lipid membranes—as a dual-functional platform for mild PTT and OXPHOS inhibition via co-delivery of NF-κB inhibitor TPCA-1. Characterization confirmed uniform size and stability. The nanoparticles showed concentration/power-dependent photothermal conversion with ≤3% efficiency loss after 4 laser cycles. In vitro, TPC@Ms induced mitochondrial dysfunction and synergized photothermal/chemo effects. In vivo, they remodeled the tumor immune microenvironment and enhanced PD-L1 blockade efficacy in murine models. This bioengineered system overcomes conventional nanodrug toxicity while enabling ATP-depletion-enhanced mild PTT, demonstrating translational potential through combined material innovation and metabolic targeting.