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This need is addressed herein through an engineering of antibody\u2010drug conjugates (ADCs) that contain an anti\u2010neoplastic drug mitomycin C, which is also a potent antimicrobial against biofilms. The ADCs designed herein release the conjugated drug without cell entry, via a novel mechanism of drug release which likely involves an interaction of ADC with the thiols on the bacterial cell surface. ADCs targeted toward bacteria are superior by the afforded antimicrobial effects compared to the non\u2010specific counterpart, in suspension and within biofilms, in vitro, and in an implant\u2010associated murine osteomyelitis model in vivo. The results are important in developing ADC for a new area of application with a significant translational potential, and in addressing an urgent medical need of designing a treatment of bacterial biofilms.<\/jats:p>","DOI":"10.1002\/advs.202301340","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T16:06:02Z","timestamp":1686240362000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Antibody\u2010Drug Conjugates to Treat Bacterial Biofilms via Targeting and Extracellular Drug Release"],"prefix":"10.1002","volume":"10","author":[{"given":"Anne","family":"Tvilum","sequence":"first","affiliation":[{"name":"Department of Chemistry Aarhus University  Aarhus C 8000 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkel I.","family":"Johansen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus N 8200 Denmark"},{"name":"Department of Infectious Diseases Aarhus University Hospital  Aarhus N 8200 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e6rke N.","family":"Glud","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nanoscience Centre (iNANO) Aarhus University  Aarhus C 8000 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Ivarsen","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nanoscience Centre (iNANO) Aarhus University  Aarhus C 8000 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda B.","family":"Khamas","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nanoscience Centre (iNANO) Aarhus University  Aarhus C 8000 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheiliza","family":"Carmali","sequence":"additional","affiliation":[{"name":"Department of Chemistry Aarhus University  Aarhus C 8000 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snehit Satish","family":"Mhatre","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nanoscience Centre (iNANO) Aarhus University  Aarhus C 8000 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ane B.","family":"S\u00f8gaard","sequence":"additional","affiliation":[{"name":"Department of Chemistry Aarhus University  Aarhus C 8000 Denmark"},{"name":"Interdisciplinary Nanoscience Centre (iNANO) Aarhus University  Aarhus C 8000 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Faddy","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Aarhus University  Aarhus N 8200 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisanne","family":"de Vor","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzan H. 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