• • MOITT exhibits a bathochromic shift to 606 nm absorption and NIR-II emission at 1080 nm, enabling deep-tissue penetration (>5 mm) and reduced autofluorescence, which is critical for clinical translation of imaging-guided phototherapy in hypoxic solid tumors.
• • Under 808 nm laser irradiation, MOITT achieves a photothermal conversion efficiency (η) of 44%, surpassing typical type I PSs (η < 30%), thereby providing sufficient hyperthermia to ablate tumors while minimizing collateral damage to adjacent healthy tissue.
• • MOITT NPs selectively accumulate in lipid droplets and initiate lipid peroxidation, triggering ferroptosis (IC50 = 2.3 µM under hypoxia) and synergistically inducing apoptosis (apoptotic index: 68% at 24 h post-irradiation), overcoming hypoxia-mediated resistance that limits conventional type II PDT.
• • In vivo, MOITT NPs enable high-resolution NIR-II fluorescence imaging of blood vessels (signal-to-noise ratio > 8) and achieve complete tumor eradication (100% survival at 60 days) in a murine model, demonstrating a viable pathway for spatiotemporal control of multimodal cell death in clinical oncology.