Environment-triggered nanoagent with programmed gas release performance for accelerating diabetic infected wound healing

Abstract

The treatment of diabetic infected wound still faces severe challenges, including drug-resistant bacterial infections, exaggerated inflammatory reactions, and dysangiogenesis. To address these issues, a programmed gas release nanoparticle (PB-SNP@SiO2, PSS NPs) were developed to effectively remove drug-resistant pathogens and remodel the microenvironment of diabetic wounds using NO and H2S, respectively. During hydrothermal synthesis, NO donor (sodium nitroprusside) was doped into Prussian blue (PB) NPs. Then bis[3-(triethoxysilyl)propyl]tetrasulfid as glutathione (GSH)-responsive H2S donor was incorporated into the silica outer layer of the PB NPs for anti-inflammatory and pro-angiogenesis applications. After receiving PSS NPs treatment, the bacteria and even bacterial biofilm could be effectively eliminated by using NO/photothermal combined antibacterial therapy upon irradiated with 808 nm laser. Simultaneously, under the triggering of endogenous GSH, the H2S gas released from PSS NPs could ameliorate the detrimental diabetic wound microenvironment by inhibiting the excessive inflammatory response (e.g., inhibiting the expression of inflammatory factors and promoting the transformation of M1 type into M2 type macrophage) and facilitating revascularization, further expediting wounds healing. Using this gas-programmed release strategies, different therapeutic gases can be release precisely for diabetic treatment, which provides a novel reference for gases combined therapy.