Halogen anion modulated metal-organic frameworks with enhanced nanozyme activities for bacterial biofilm disruption

There is an urgent need to develop new nanozymes with enhanced catalytic activities to combat bacterial infections, which have become increasingly challenging due to the misuse of antibiotics and the difficulties of new antibiotic discovery. Here, we employed a new strategy against bacterial biofilms by introducing halide anions to modulate the crystal facets of ZIF-L metal-organic frameworks (MOFs) and then loading chloroquine to form Ch@ZIF-L. The modulation of crystal facets significantly enhanced the oxidase activities of ZIF-L, which can be significantly changed by modulation of its crystal facets, with the hexagonal ZIF-L (ZIF-L-H-Cl) structure showing the highest oxidase activity. At pH 6.0, over 80% of chloroquine was released from Ch@ZIF-L-H-Cl within 8 hours, altering the DNA conformation of bacterial biofilms and disrupting the extracellular polymeric substances (EPSs). The generation of singlet oxygen catalyzed by ZIF-L-H-Cl can effectively kill bacteria at the infected wound site. The composite nanozyme of Ch@ZIF-L-H-Cl, when treated at 100 μg mL^-1, exhibited no adverse effects on normal cell growth or hemolysis. Our in vivo experiments demonstrated an 85% reduction of the wound area by day 8 and a rapid recovery of body weight in mice with wounds infected with Staphylococcus aureus (S. aureus) biofilms. Furthermore, substantial reductions in bacterial counts were observed in both wounds and blood samples in the mice, highlighting the great potential of Ch@ZIF-L-H-Cl in combating bacterial biofilm infections.