Photothermally Induced Vapor Nanobubbles Enable Disruption and Antibiotic-Improved Responsiveness in Uropathogenic...

Treating bacterial biofilms remains a major clinical challenge, particularly in uropathogenic infections where the dense extracellular matrix impedes antibiotic access and protects tolerant bacterial populations. In this work, we explored a nanomaterial-based strategy to improve antibiotic responsiveness by combining iron oxide nanoparticles (IONPs) with pulsed laser irradiation to induce vapor nanobubble (VNB)-mediated disruption of a mature flow-grown uropathogenic E. coli CFT073 biofilm. We tested three nanoparticle sizes (70 nm, 130 nm, and 500 nm) and identified IONP₅₀₀ as the most effective formulation for generating VNBs upon irradiation with 532 nm nanosecond laser pulses, with a VNB threshold of 0.56 J/cm² per pulse. In the mature biofilm model, the combined IONP₅₀₀ + ciprofloxacin + laser treatment significantly enhanced antibiotic activity compared with ciprofloxacin alone, increasing dead biomass from approximately 16% to 23%, corresponding to a 39-45% relative increase, as quantified by COMSTAT analysis and one-way ANOVA with Tukey's post-hoc test. The combined treatment also reduced total biofilm biomass and increased biofilm porosity by 55.8% compared with ciprofloxacin alone, supporting a mechanism based on VNB-mediated matrix disruption and improved antibiotic access. Overall, these results support the use of photothermally active, biocompatible IONPs as a promising complementary strategy to enhance the efficacy of conventional antibiotics against persistent biofilm-associated infections.