Construction of Self-activated Cascade Metal-Organic Framework/Enzyme Hybrid Nanoreactors as Antibacterial Agents

Metal organic frameworks (MOFs) served as peroxidase-like artificial enzymes have been recently adopted for wide applications including therapy, pollution degradation, biosensing and so on. However, most of MOFs mimicking peroxidase cannot perform with the utmost efficiency under certain biological circumstances, such as bacterial infections. This is mainly because that the peroxidase-like MOFs exhibit highest activity at pH of 3-4, while bacterial infections cannot lower the environmental pH to the optimal value. This problem significantly restrains the therapy effect. Herein, self-activated cascade MOF/enzyme hybrid nanoreactors (MIL@GOx-MIL NRs) based on MIL (Materials of Institute Lavoisier) and GOx (Glucose oxidase) were successfully constructed through a two-step procedure. GOx was successfully loaded in the MIL shells and onto their surface as well. The GOx can catalyze the production of gluconic acid that reduces the pH value to around 4, at which the MIL@GOx-MIL NRs perform the highest cascade reaction activity. The continually produced hydrogen peroxide (H₂O₂) can be subsequently catalyzed by MIL NPs to generate highly toxic hydroxyl radicals (HO^•) for antibacterial application. Thus, MIL@GOx-MIL NRs can significantly inhibit methicillin-resistant staphylococcus aureus (MRSA) growth and biofilm formation.