H2O2 self-supplied CuFeOx nanosystem as fenton-like reaction agents for endogenous/exogenous responsive synergetic antibacterial therapy

Chemodynamic therapy (CDT) based on nanozyme has attracted extensive attention in the treatment of bacterial infections. However, the catalytic activity of nanozymes and the infection microenvironments severely limit CDT antibacterial efficacy. Herein, a near-infrared-controlled antibacterial nanoplatform (CuFeOx/IR825@PCM) is developed by encapsulating Cu-Fe peroxide nanoparticles (CuFeOx) and the photothermal agents (IR825) in the thermal-sensitive organic phase change material (PCM). The unique wax sealing property of PCM helps to improve the stability of CuFeOx. After administration, the hyperthermia effect induced by IR825 under near infrared (NIR) irradiation would induce the melting of PCM shell and rapidly release the CuFeOx. In response to the lower pH in the inflammatory microenvironment, CuFeOx nanoparticles (NPs) would be further decomposed to release a large amount of exogenous hydrogen peroxide (H2O2), which makes up for the deficiency of limited endogenous H2O2 and improves the performance of CDT. In addition, the low pH of bacterial infection microenvironment resulted in the decomposition of CuFeOx to generate a large amount of Cu2+/Cu+, Fe3+/Fe2+ and H2O2. The released Cu2+ and Fe3+ were reduced to Cu+ and Fe2+ by endogenous glutathione (GSH), thus depleting the GSH. With the help of combination therapy of photothermal therapy (PTT) and CDT, in vivo and in vitro experiments proved that CuFeOx/IR825@PCM could effectively destroy the bacterial structure and induce bacterial inactivation with ignored side toxicity.