From Light to Cure: Precision Phototherapies for Antibiotic-Refractory Biofilm Infections.

Bacterial biofilms serve as formidable barriers in antimicrobial therapy and are central to the emergence and propagation of antimicrobial resistance. Their compact extracellular polymeric matrix, metabolic heterogeneity, and quorum-sensing-mediated resistance gene expression collectively endow biofilms with exceptional defense against conventional antibiotics. This review highlights the structural-functional complexity of biofilms and focuses on emerging phototherapeutic strategies-photothermal therapy (PTT) and photodynamic therapy (PDT)-as promising biofilm-targeted approaches. PTT employs near-infrared light to induce localized hyperthermia, disrupting bacterial membranes and enhancing drug penetration. PDT generates reactive oxygen species via photoactivated photosensitizers, leading to oxidative destruction of both cells and extracellular polymeric substances. These strategies offer metabolic independence, precise spatiotemporal control, and efficacy against dormant pathogens. Recent advances in smart nanoplatforms enable the integration of PTT/PDT with responsive drug delivery, imaging guidance, and immune modulation, achieving multimodal, precision antimicrobial effects. Furthermore, synergistic combinations with enzymatic degradation, immune intervention, and antibiotics show promise in treating chronic and biofilm-associated infections. We conclude by outlining translational challenges and strategic directions for clinical application, underscoring the potential of phototherapy to reshape infection management beyond antibiotic dependence.