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

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 H 2 O 2 levels and a near-neutral pH at infection sites. Herein, a glucose-fueled and H 2 O 2 self-supplying •OH nanogenerator (GOx-Fe 3 O 4 @MIL) based on cascade catalytic reactions is successfully constructed by immobilizing glucose oxidase (GOx) on the surface of Fe 3 O 4 NPs-encapsulated MIL88B–NH 2. MIL88B–NH 2 (MIL NPs), a peroxidase-mimicking enzyme, immobilizes and protects GOx while synergistically enhancing the CDT effect of Fe 3 O 4 NPs. GOx can continuously convert glucose into gluconic acid and H 2 O 2. The former reduces the pH value to approximately 4, at which point Fe 3 O 4 @ MIL NPs exhibit the highest reaction activity. The continually produced H 2 O 2 is used for subsequent catalysis of activated Fe 3 O 4 @MIL NPs to generate highly toxic •OH for antibacterial applications, avoiding the direct use of relatively high concentrated and toxic H 2 O 2. 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. [ABSTRACT FROM AUTHOR]