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Their compact extracellular polymeric matrix, metabolic heterogeneity, and quorum\u2010sensing\u2013mediated resistance gene expression collectively endow biofilms with exceptional defense against conventional antibiotics. This review highlights the structural\u2010functional complexity of biofilms and focuses on emerging phototherapeutic strategies\u2014photothermal therapy (PTT) and photodynamic therapy (PDT)\u2014as promising biofilm\u2010targeted approaches. PTT employs near\u2010infrared 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\u2010associated 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.<\/jats:p>","DOI":"10.1002\/anie.202510900","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T07:21:52Z","timestamp":1757748112000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["From Light to Cure: Precision Phototherapies for Antibiotic\u2010Refractory Biofilm Infections"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2665-9036","authenticated-orcid":false,"given":"Qihang","family":"Ding","sequence":"first","affiliation":[{"name":"Engineering Research Center for Pharmaceuticals and Equipments of Sichuan Province Sichuan Industrial I of Antibiotics School of Pharmacy Chengdu University  Chengdu 610106 P.R. 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