{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:10:33Z","timestamp":1788869433321,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"42","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82504654"],"award-info":[{"award-number":["82504654"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005090","name":"Beijing Nova Program","doi-asserted-by":"publisher","award":["20220484116"],"award-info":[{"award-number":["20220484116"]}],"id":[{"id":"10.13039\/501100005090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Antibody\u2010antibiotic conjugates (AACs) provide a transformative platform for eradicating intracellular methicillin\u2010resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA). However, current AACs largely follow antibody\u2010drug conjugates (ADCs) design principles and rely on host\u2010lysosomal proteases for activation, rendering them ineffective against extracellular (planktonic) bacteria. Furthermore, we demonstrate that high bacterial burden induces host\u2010lysosomal dysfunction, fundamentally compromising the efficacy of host\u2010dependent AACs against intracellular reservoirs. To address these limitations, we developed a pathogen\u2010centric AAC (AZO\u2010AAC) featuring an azobenzene\u2010based linker that is triggered by bacterial\u2010secreted azoreductase. This strategy shifts the activation mechanism from host\u2010cell machinery to the pathogen itself, enabling antibiotic release independent of host\u2010cell integrity. Surprisingly, our designed AZO\u2010AAC achieves nanomolar\u2010scale eradication of both planktonic and intracellular MRSA, reaching levels below the limit of detection in scenarios where traditional AACs fail. In murine models of peritonitis and septicemia, a single dose (60\u00a0mg\/kg) of AZO\u2010AAC resulted in a six\u2010log reduction in bacterial burden and the preservation of normal tissue architecture. By decoupling activation from host\u2010cell status, this pathogen\u2010responsive platform provides a robust strategy for the targeted elimination of complex, multi\u2010niche MRSA infections.\n                  <\/jats:p>","DOI":"10.1002\/advs.75541","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T09:52:47Z","timestamp":1778493167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pathogen\u2010Centric Activation of an Azoreductase\u2010Responsive Antibody\u2010Antibiotic Conjugate for the Targeted Eradication of MRSA"],"prefix":"10.1002","volume":"13","author":[{"given":"Qi","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Pharmacy Qingdao University  Qingdao China"},{"name":"Academy of Military Medical Sciences  Beijing China"},{"name":"National Engineering Research Center for the Emergency Drug  Beijing 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