Bidirectional ROS Modulation for Programmed Anti-Infective and Anti-Inflammatory Therapy With Au-Cu₂O/MXene...

Chronic bacterial infections pose a therapeutic challenge in eliminating bacteria while suppressing inflammation. Conventional antibiotics are often limited by drug resistance and poor biofilm penetration, contributing to a global health threat of antibiotic misuse. Reactive oxygen species (ROS) modulation offers a promising alternative, yet requires precise balance: insufficient ROS compromises antibacterial efficacy, but excess exacerbates inflammation. Here, we present a bidirectional ROS-regulation strategy for programmed antibacterial and anti-inflammatory therapy using Au-edged cuprous oxide (Cu₂O) nanocubes on MXene (Au-Cu₂O/MXene). Under near-infrared (NIR) irradiation, this nanocomposite induces moderate ROS, eliminating >99% of planktonic bacteria and >97% of mature biofilms. After cessation of NIR irradiation, the nanocomposite itself switches to scavenge the residual excessive ROS in the inflammatory microenvironment, which alleviates oxidative stress. Our skin wound infection model further demonstrates that Au-Cu₂O/MXene markedly reduces bacterial burden, suppresses inflammatory responses, and accelerates wound closure. Theoretical computations reveal that Au-capping weakens O₂ adsorption through weak O 2p-Au 5d orbital hybridization and hinders photogenerated electron transfer with high work function, suppressing ROS overproduction; it also lowers the free energy barrier for H₂O/O₂ desorption, promoting ROS decomposition. This work offers an effective antibiotic-free immunomodulation strategy for programmed biofilm eradication, infected wound repair, and inflammation suppression via context-dependent ROS modulation.