H₂O₂ self-supplied CuFeO_x 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 (CuFeO_x/IR825@PCM) is developed by encapsulating Cu-Fe peroxide nanoparticles (CuFeO_x) 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 CuFeO_x. After administration, the hyperthermia effect induced by IR825 under near infrared (NIR) irradiation would induce the melting of PCM shell and rapidly release the CuFeO_x. In response to the lower pH in the inflammatory microenvironment, CuFeO_x 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 CuFeO_x 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 CuFeO_x/IR825@PCM could effectively destroy the bacterial structure and induce bacterial inactivation with ignored side toxicity.