Water-soluble metal-organic cages crosslinked injectable hydrogel for multi-modal synergistic therapy

Despite the excessive of antibiotics causes the emergence of multidrug-resistant (MDR) bacteria, antibiotic therapy remains the most effective and fastest-acting strategy currently available. Water-soluble metal–organic cages (MOCs) are ideal platforms for enhancing antibiotic efficacy through host–guest interactions and mediating the transformation of infected microenvironments due to their defined sizes, shapes, and high modularization of ligands. Here, we have developed a novel water-soluble MOCs crosslinked injectable hydrogel antibacterial platform (GG-ENR@Fe Gel) with multi-mode treatment strategies. In this platform, guar gum (GG), as a carrier, exhibits excellent moisturizing property, biosafety and rapid degradation ability, making it suitable as a medical dressing. Water-soluble MOCs (Fe-1•SO4) was employed in the hydrogel to enhance the solubility and antibacterial efficacy of enrofloxacin (ENR) through host–guest interaction, further triggering additional crosslinking among the GG polymers. Furthermore, after effective adhesion to the infected wound, the Fe-1•SO4 can generate singlet oxygen (1O2) by PDT and rapidly produce massive hydroxyl radicals (•OH) through Fenton-like reaction in the infected microenvironment. This study demonstrates that the water-soluble MOCs is a versatile and synergistic therapeutic platform that can provide promising strategies for treatment of bacterial infections.