Nanofibers fortified with synergistic defense route: A potent wound dressing against drug-resistant bacterial infections

The escalating utilization of antibiotics and the subsequent evolution of drug resistance among patients have created an urgent imperative to advance antibiotic-free treatment methodologies. In this work, we have developed nanofibrous wound dressings with synergistic antibacterial activity. Our approach involves the layerwise co-assembly of benzalkonium chloride (BC) and metal–organic framework nanoparticles (MOFs, PCN-224) onto poly(ε-caprolactone) (PCL) electrospun nanofibrous membranes (ENMs) using a tannic acid (TA)-assisted adhesion strategy. The electrostatic interaction between the pyrogallol groups of TA and the charged BC under alkaline conditions enables this strategy. Furthermore, the catechol motifs of TA enhance the ENMs' versatility in adhesion and serve as reactive linkers for further co-assembly of PCN-224. The resulting PCL/TA@BC/MOFs (PTM) composites exhibit high loading efficiency of PCN-224, excellent physiological stability, desirable biocompatibility, and synergistic bactericidal therapy. The PTM composites employ dual bacterial defense mechanisms, with PCN-224 converting illumination into singlet oxygen (1O2) for photodynamic effects, while the hydrophobic alkyl chain of BC inhibits bacterial growth by disruption of lipid packing of the bacterial membrane. In vitro and in vivo experiments demonstrate that the PTM composites achieve bactericidal rates exceeding 99.99% against Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA) with only 10 min of irradiation. This breakthrough contributes to the rapid recovery of MRSA-infected wound sites with minimal biological burden. Overall, our rational design of a wound dressing with synergistic bactericidal therapeutic effects presents a novel intervention for enhancing wound disinfection in clinical settings.