Fe₂N@C nanomaterials: Synergistic PTT/CDT/NO for the dynamic therapy of diabetic foot ulcer

Diabetic foot ulcer (DFU) is one of the most severe complications of diabetes, and its multiple pathological factors render treatment more challenging. We synthesized Fe₂N@C nanomaterials to integrate synergistic photothermal therapy/chemical dynamic therapy/nitric oxide (PTT/CDT/NO) for DFU therapy. First, Fe₂O₃ and urea were used as precursors to synthesize Fe₂N@C nanomaterials via nitridation. The nanomaterial can serve as a new NO donor that releases NO triggered by H⁺ and reactive oxygen species (H₂O₂ and O₂). Furthermore, Fe₂N@C possess superhigh peroxidase (POD)-like activity (V_max = 21.1 Ms.^-1, pH 5.5), catalyzing endogenous H₂O₂ into hydroxyl radicals (OH). POD activity can also amplify NO and peroxynitrite (ONOO^-) production. In addition, Fe₂N@C nanomaterials reveal high near-infrared II (NIR-II) light harvest and photothermal conversion efficiency (43.94%). Hyperthermia also synergistically boosts POD-like activity and NO release. Under NIR-II laser irradiation, the combination of PTT/CDT and high NO concentration of can quickly clear bacterial infection. In addition, NO can down-regulate the expression of heat shock proteins (HSPs) to amplify PTT performance. Then, the mild NO supply (without irradiation) further facilitates the reversal of inflammation (M2 macrophage polarization) and tissue regeneration (angiogenesis). This dynamic synergistic therapy promotes fast normal DFU healing.