NIR-II Photoacoustic-Cavitation Boosted Metabolic Reprogramming Regulation Toward the Localized TNBC Growth Inhibition

Triple-negative breast cancer (TNBC) treatment with traditional phototherapeutics generally suffers from short light penetration depth and limitations of the hypoxic tumor microenvironment. Developing effective therapeutic modalities tailored to TNBC's features remains highly desirable yet challenging. Herein, we propose a near-infrared dual windows (NIR-II) photoacoustic (PA) cavitation-based strategy to amplify oxidative stress and induce metabolic disruption in TNBC cells, achieving effective tumor suppression. With a fabricated nanoagent (DTG), we integrated the oxygen-independent therapeutic effects of photomechanical damage, cavitation-promoted oxidative damage and glucose oxidase (GOx)-mediated glucose depletion. Specifically, under NIR-II pulsed laser (PL) irradiation, PA cavitation generates collapsing bubbles and shock waves, causing mechanical injury to tumor cells. Meanwhile, GOx depletes intratumoral glucose, blocking glycolysis, reducing adenosine triphosphate (ATP) production, and generating hydrogen peroxide (H₂O₂) that would be further converted into more toxic hydroxyl radicals (^•OH) by the photocavitation to suppress the tumors effectively. In addition, the strong NIR-II PA signal produced from the DTG facilitates high-resolution deep-tissue imaging to provide precise therapeutic guidance. Thus, these findings establish the multimodal strategy as a potent candidate for TNBC management.