Photothermal-triggered release of alkyl radicals and cascade generation of hydroxyl radicals via a versatile hybrid nanocatalyst for hypoxia-irrelevant synergistic antibiofilm therapy

Well-designed nanocatalysts capable of generating free radicals have recently shown promising potential for treating bacterial biofilm infections. However, the biofilm microenvironments such as hypoxia and over-expressed glutathione (GSH) seriously limit their biomedical applications. To address these issues, we herein construct a dual free radical nanogenerator (MnO2/GOx/AIBI) by loading glucose oxidase (GOx) and thermal-labile azo initiator (AIBI) onto the flower-like MnO2 with high loading capacity for the hypoxia-irrelevant treatment of biofilm-associated bacterial infections. On the one hand, MnO2/GOx/AIBI nanocomposites can generate hydroxyl radicals by glucose-fueled cascade catalytic reactions between GOx and MnO2 for efficient O2– and H2O2-self-supplying chemodynamic therapy (CDT). On the other hand, MnO2 can provide local photonic hyperpyrexia, which not only triggers the O2-independent generation of alkyl radicals for photothermal dynamic therapy (PTDT), but also enhances the CDT efficacy by accelerating the release of Fenton-type Mn2+. Besides, MnO2 can degrade GSH over-expressed in the infection sites, improving the synergistic CDT/PTDT therapeutic effectiveness by redox dyshomeobasis. The hybrid MnO2/GOx/AIBI nanocatalysts exhibit satisfactory in vitro and in vivo antibacterial and antibiofilm performances with minimal toxic side effects. Taken together, the developed hypoxia-irrelevant dual-mode synergistic antibacterial nanoplatform can effectively overcome the interferences of biofilm microenvironments, showing a promising potential for future biomedical applications.