H2S-removing UiO-66 MOFs for sensitized antibacterial therapy

Abstract

Antibiotic tolerance is implicated in difficult-to-treat infections and the development and spread of antibiotic resistance. The high storage capacities and excellent biocompatibilities of UiO-66-based metal–organic frameworks (MOFs) have made them emerging candidates as drug-delivery vectors. In view of hydrogen sulfide (H₂S) having been associated with the development of intrinsic resistance to antibacterial agents, we designed a strategy to potentiate existing antibiotics by eliminating bacterial endogenous H₂S. We efficiently fabricated an antibiotic enhancer Gm@UiO-66-MA to remove bacterial H₂S and sensitize an antibacterial by modifying UiO-66-NH₂ with maleic anhydride (MA) and then loading it with gentamicin (Gm). UiO-66-MA achieved the removal of bacterial endogenous H₂S and the destruction of bacterial biofilm by selectively undergoing Michael addition with H₂S. Moreover, Gm@UiO-66-MA further enhanced the susceptibility of tolerant E. coli to Gm after reducing bacterial intracellular H₂S levels. An in vivo skin wound healing experiment confirmed that Gm@UiO-66-MA could greatly reduce the risk of bacterial reinfection and accelerate wound healing. Overall, Gm@UiO-66-MA offers a promising antibiotic sensitizer for minimizing bacterial resistance and a therapeutic strategy for tolerant bacteria-related refractory infections.