Acid-activated ROS generator with folic acid targeting for bacterial biofilm elimination

Many medical and chemical applications require the precise supply of antimicrobial components in a controlled manner at the location of mature biofilm deposits. This work reports a facile strategy to fabricate nanoscale metal-organic frameworks (NMOFs) coencapsulating the antibacterial ligand (lysine carbon dots, Lys-CDs) and targeted drug (folic acid, FA) in one pot to improve antibiofilm efficiency against established biofilms. The resulting products are characterized by transmission electron microscopy, field-emission scanning electron microscopy, powder x-ray diffraction, and ultraviolet-visible spectroscopy. The results show that Lys-CDs could coordinate with Zn²⁺ and the adding of FA inhibits the coordination of Lys-CDs with central ions of Zn. The Lys-CDs and FA are successfully exposed with the NMOFs disintegrating in the acid environment of bacterial metabolites. We are surprised to find a sharp increase of reactive oxygen species (ROS) inside the bacterial cells by FA functionalizing NMOFs, which undoubtedly enhance the antibacterial and antibiofilm activity. The as-synthesized ZIF-8-based nanocomposites also show the peroxidase-like activity in an acid environment, and produce extremely active hydroxyl radicals resulting in the improved antibacterial and antibiofilm activity. The possible mechanisms of antibacterial activities indicate that the presence of FA is significant in the sense of targeting bacteria. This study shows a novel approach to construct acid stimulation supply system which may be helpful for the research of antibiofilms.