Fe3O4 NPs-encapsulated metal-organic framework/enzyme hybrid nanoreactor for drug-resistant bacterial elimination via enhanced chemodynamictherapy

Abstract

As a potential tool for combating bacterial infections, chemodynamic therapy (CDT), which utilizes the highly toxic hydroxyl radical (•OH), has shown tremendous promise. Its antibacterial efficacy, however, is compromised by insufficient H2O2 levels and a near-neutral pH at infection sites. Herein, a glucose-fueled and H2O2 self-supplying •OH nanogenerator (GOx-Fe3O4@MIL) based on cascade catalytic reactions is successfully constructed by immobilizing glucose oxidase (GOx) on the surface of Fe3O4 NPs-encapsulated MIL88B–NH2. MIL88B–NH2 (MIL NPs), a peroxidase-mimicking enzyme, immobilizes and protects GOx while synergistically enhancing the CDT effect of Fe3O4 NPs. GOx can continuously convert glucose into gluconic acid and H2O2. The former reduces the pH value to approximately 4, at which point Fe3O4@ MIL NPs exhibit the highest reaction activity. The continually produced H2O2 is used for subsequent catalysis of activated Fe3O4 @MIL NPs to generate highly toxic •OH for antibacterial applications, avoiding the direct use of relatively high concentrated and toxic H2O2. In vitro and in vivo results indicate that the designed self-activated nanoreactor can significantly inhibit methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Acinetobacter baumannii (MDR-AB) growth with negligible biotoxicity.