Self-enhanced ROS generation by responsive co-delivery of H2O2 and O2 based on a versatile composite biomaterial for hypoxia-irrelevant multimodal antibiofilm therapy

Reactive oxygen species (ROS) such as hydroxyl radicals (OH) and singlet oxygen (1O2) have emerged as promising therapeutic agents for combating biofilm-associated bacterial infections. However, the hypoxic microenvironments in the biofilms severely hinder the ROS production. Herein, we have rationally integrated copper peroxide (CP) and indocyanine green (ICG) into a polydopamine (PDA) nanoparticle to construct a versatile hybrid nanoplatform (PDA/CP/ICG), which can enhance ROS generation for highly efficient biofilm elimination by relieving hypoxic microenvironment. When the PDA/CP/ICG accumulates at the infection site or biofilm, the acidic microenvironment triggers the co-release of Cu2+ and H2O2, and the former can catalyze the conversion of self-supplied H2O2 into OH via a Fenton-like reaction and consume the overexpressed antioxidant glutathione (GSH) to further promote the oxidative stress. Moreover, with the help of an 808 nm laser, the hyperpyrexia caused by PDA induces the decomposition of CP into O2 that is immediately converted by ICG into 1O2. The PDA/CP/ICG shows satisfactory antibacterial and antibiofilm effect due to the self-amplified production of OH and 1O2, and outstanding wound healing with good in vivo biosafety. Overall, this study provides a facile paradigm in ROS-based biofilm elimination, and the proposed hypoxia-irrelevant bactericidal nanoplatform has great potential for future biomedical applications.