Dye‐Sensitized Semiconductor‐Based Type‐I Photosensitizers With Precise Energy‐Level Matching and Ultrafast Electron Transfer for Hypoxic Tumor Therapy

ABSTRACT Intractable hypoxia in solid tumors remains a major obstacle for conventional type‐II photodynamic therapy. We report a dye‑sensitized semiconductor strategy to construct high‐efficiency, low oxygen‐dependent type‐I photosensitizers by anchoring proper dyes to zinc oxide ( ZnO ) nanoparticles. Guided by precise energy‐level engineering, a thermodynamic threshold is established to enable efficient interfacial electron transfer. Femtosecond transient absorption spectroscopy directly captures ultrafast electron injection on the picosecond timescale, a process that effectively outcompetes radiative decay and suppresses charge recombination. The resulting ZnO‐Cy7@PDA nanoplatform mediates a unique dual‐pathway redox synergy: the electron‐rich ZnO conduction band drives robust generation of • O 2– and • OH even under extreme hypoxia, while the electron‐deficient dye species catalytically depletes endogenous NADH and GSH. This combined action induces severe oxidative stress, triggering a pro‐death autophagy–ferroptosis cascade that effectively overcomes therapeutic resistance. This work provides a universal physicochemical blueprint for semiconductor‐based phototherapeutics and offers insights bridging ultrafast photonics and organelle‐specific therapy.