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

Fe 2 N@C nanospheres integrate NO release, PTT, and CDT for DFU therapy. • NIR-II-triggered hyperpyrexia amplifies POD-like activity of Fe 2 N@C. • Inorganic Fe 2 N@C acts as a novel NO donor with high release capacity. • Acidic biofilm microenvironment facilitates NO release and CDT activity. • Dynamic therapy possesses great potential on infective DFU therapy. Diabetic foot ulcer (DFU) is one of the most severe complications of diabetes, and its multiple pathological factors render treatment more challenging. We synthesized Fe 2 N@C nanomaterials to integrate synergistic photothermal therapy/chemical dynamic therapy/nitric oxide (PTT/CDT/NO) for DFU therapy. First, Fe 2 O 3 and urea were used as precursors to synthesize Fe 2 N@C nanomaterials via nitridation. The nanomaterial can serve as a new NO donor that releases NO triggered by H + and reactive oxygen species (H 2 O 2 and O 2 ). Furthermore, Fe 2 N@C possess superhigh peroxidase (POD)-like activity (V max  = 21.1 Ms. −1 , pH 5.5), catalyzing endogenous H 2 O 2 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. Download: Download high-res image (259KB) Download: Download full-size image