An NIR-II light-responsive nanoplatform for photothermal and enhanced photodynamic synergistic therapy toward drug-resistant bacterial infection and hypoxia relief in subcutaneous wound healing

The drug-resistant bacterial infection has seriously threatened human health and thus it is urgent to develop new and effective drugs to overcome the antibiotic resistance crisis. Herein, a near-infrared-II (NIR-II) region light-responsive Pd rough nanoshells on metal-organic framework (MOF) of UiO-66-NH2 (UiO-66-NH2@Pdshell) has been developed for the first time, which was further loaded with the photosensitizer IR780 to ultimately yield UiO-66-NH2@Pdshell-IR780 (UPI) as the core-shell theranostic nanoplatform. The Pd rough nanoshells demonstrate promising photothermal conversion efficiency, superoxide dismutase (SOD)-like activity, and light-enhanced catalase (CAT)-like activity. In the non-healing wound inflammatory microenvironment with overexpression of reactive oxygen species (ROS) caused by subcutaneous bacterial infection, Pd rough nanoshells in UPI transforms ROS, such as O2•−, into H2O2 and efficiently catalyzes the decomposition of the formed and endogenous H2O2 to produce O2. The O2 production process could be enhanced by NIR-II light to facilitate photodynamic efficacy of IR780 to prime rapid clearance of methicillin-resistant Staphylococcus aureus (MRSA) through biofilm inhibition, along with down-regulation of hypoxia inducible factor-1α (HIF-1α) and relief of inflammation, thus promote wound healing. Moreover, UPI exhibits negligible biotoxicity in vitro and in vivo. This work provides a method for preparing promising Pd-based nanomaterials toward subcutaneous infection treatment and wound healing.