Microneedle-mediated delivery of an nir-triggered nanoagent for synergistic anti-biofilm infection therapy

Background: Post-surgical biofilm infections present a major clinical challenge due to their exceptional tolerance to antibiotics and the physical barrier of extracellular polymeric substance (EPS), calling for innovative non-antibiotic therapeutic strategies. Methods: We engineered a synergistic platform by constructing curcumin-loaded iron-based metal-organic framework (MIL@Cur) nanoparticles and incorporating them into a dissolvable hyaluronic acid-based hydrogel to fabricate composite microneedles (MIL@Cur microneedle (FCMN)). The system was characterized for its physicochemical properties and evaluated for antibacterial efficacy in vitro and in a murine methicillin-resistant staphylococcus aureus (MRSA)-infected wound model. Results: The MIL@Cur nanoparticles demonstrated well-defined morphology, high photothermal conversion efficiency (reaching >50°C under laser irradiation), and pH-responsive drug release. In vitro, MIL@Cur with laser irradiation achieved synergistic bacterial eradication through photothermal therapy and ironoverload-induced chemodynamic therapy (CDT), while also disrupting pre-formed biofilms and inhibiting new biofilm formation via quorum sensing (QS) suppression. The FCMN patch exhibited excellent mechanical strength and efficient transdermal delivery. In vivo, the FCMN + Laser group showed accelerated wound closure, ∼ 2-log reduction in bacterial load, enhanced collagen deposition and angiogenesis, and no systemic toxicity. Conclusions: This microneedle-mediated platform effectively combines multiple antimicrobial modalities, providing a powerful and translatable strategy for treating stubborn biofilm infections and promoting wound repair.