Nitrogen Vacancy-rich Carbon Nitride Anchored with Iron Atoms for Efficient Redox Dyshomeostasis Under Ultrasound Actuation

Traditional Fe-based Fenton reaction for inducing oxidative stress is restricted by random charge transfer without oriental delivery, and the resultant generation of reactive oxygen species (ROS) is always too simplistic to realize a satisfactory therapeutic outcome. Herein, FeN/CN nanosheets rich in nitrogen vacancies are developed for high-performance redox dyshomeostasis therapy after surface conjugation with polyethylene glycol (PEG) and cyclic Arg-Gly-Asp (cRGD). Surface defects in FeN/CN serve as electron traps to drive the directional transfer of the excited electrons to Fe atom sites under ultrasound (US) actuation, and the highly elevated electron density promote the catalytic conversion of HO into ·OH. Meanwhile, energy band edges of FeN/CN favor the production of O upon interfacial redox chemistry, which is enhanced by the optimal separation/recombination dynamics of electron/hole pairs. Moreover, intrinsic peroxidase-like activity of FeN/CN contributes to the depletion of reductant glutathione (GSH). Under the anchoring effect of cRGD, PEGylated FeN/CN can be efficiently enriched in the tumorous region, which is ultrasonically activated for concurrent ROS accumulation and GSH consumption in cytosolic region. The deleterious redox dyshomeostasis not only eradicates primary tumor but also suppresses distant metastasis via antitumor immunity elicitation. Collectively, this study could inspire more facile designs of chalybeates for medical applications.