Photothermal-driven surface redox reconstruction of Mn3+-engineered α-MoO3/MnOx nanozyme for triple-negative breast cancer therapy.

Abstract

Triple-negative breast cancer (TNBC) remains a highly aggressive malignancy with limited therapeutic options. Herein, a Mn3+-engineered α-MoO3/MnOx (MM) nanozyme was developed for synergistic photothermal and chemodynamic therapy of TNBC. The strongly coupled MM heterointerface facilitated efficient electron transfer and enabled photothermal-driven surface redox reconstruction under near-infrared (NIR) irradiation. As a result, MM triggered a self-sustaining Mn3+/Mn2+ redox cycle, leading to continuous glutathione depletion and reactive oxygen species (ROS) generation. Simultaneously, oxidative dissolution of molybdenum species released molybdate ions that disrupted phosphate metabolism and inhibited ATP synthesis, resulting in metabolic collapse. Through the synergistic effects of redox catastrophe and energy deprivation, MM effectively suppressed TNBC cell proliferation and induced apoptosis. In vivo T1-weighted magnetic resonance imaging demonstrated efficient tumor accumulation of MM. Furthermore, MM combined with NIR irradiation significantly inhibited tumor growth in 4T1 tumor-bearing mice with favorable biosafety. This work presents a photothermal-responsive Mn3+-engineered nanozyme that integrates sustained redox cycling and metabolic disruption, providing a promising strategy for TNBC therapy.