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In response to the global threat of antimicrobial resistance, bacteria\u2010responsive nanostructured drug delivery systems have emerged as a promising alternative to conventional broad\u2010spectrum antimicrobials. These systems release therapeutics selectively in response to bacterial presence or to their secreted enzymes, toxins, antigens, or extracellular biomarkers, enabling precise activation at infection sites while minimizing off\u2010target effects. Bacterial components such as membrane proteins, signaling molecules, biofilm\u2010associated glycolipids, and enzymes (e.g., lipase, hyaluronidase) serve as triggers for these smart carriers. Exopolysaccharides are also commonly targeted using nanocarriers with complementary recognition elements. Such systems are often surface\u2010modified or loaded with antimicrobials for on\u2010demand release. Benefits include enhanced selectivity, reduced side effects, improved biofilm penetration, higher intracellular accumulation, and potential for personalized therapy. A variety of materials\u2014including lipid\u2010based carriers, metal nanoparticles, polymer nanoparticles, and inorganic nanomaterials\u2014have been engineered to release antimicrobials only in the presence of pathogenic bacteria, often offering dual therapeutic effects (e.g., anti\u2010inflammatory). Furthermore, many platforms integrate multiple antimicrobial mechanisms, reducing the likelihood of resistance development. This review highlights recent preclinical studies validating bacteria\u2010responsive nanosystems and underscores their advantages over passive drug delivery and conventional free antimicrobials.<\/jats:p>","DOI":"10.1002\/adma.202510355","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T04:51:56Z","timestamp":1756356716000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Bacteria\u2010Responsive Nanostructured Drug Delivery Systems for Targeted Antimicrobial Therapy"],"prefix":"10.1002","volume":"38","author":[{"given":"Guillermo","family":"Landa","sequence":"first","affiliation":[{"name":"Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA) CSIC\u2010Universidad de Zaragoza  Zaragoza 50009 Spain"},{"name":"Department of Chemical and Environmental Engineering University of Zaragoza  Campus R\u00edo Ebro\u2010Edificio I+D, C\/ Poeta Mariano Esquillor S\/N Zaragoza 50018 Spain"},{"name":"Health Research Institute Aragon (IIS Aragon)  Zaragoza 50009 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gracia","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Health Research Institute Aragon (IIS Aragon)  Zaragoza 50009 Spain"},{"name":"Department of Pharmacology Physiology and Legal and Forensic Medicine, Facultad de Medicina\u2010Edificio A University of Zaragoza  C\/Domingo Miral, S\/N Zaragoza 50009 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Irusta","sequence":"additional","affiliation":[{"name":"Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA) CSIC\u2010Universidad de Zaragoza  Zaragoza 50009 Spain"},{"name":"Department of Chemical and Environmental Engineering University of Zaragoza  Campus R\u00edo Ebro\u2010Edificio I+D, C\/ Poeta Mariano Esquillor S\/N Zaragoza 50018 Spain"},{"name":"Health Research Institute Aragon (IIS Aragon)  Zaragoza 50009 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3165-0156","authenticated-orcid":false,"given":"Manuel","family":"Arruebo","sequence":"additional","affiliation":[{"name":"Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA) CSIC\u2010Universidad de Zaragoza  Zaragoza 50009 Spain"},{"name":"Department of Chemical and Environmental Engineering University of Zaragoza  Campus R\u00edo Ebro\u2010Edificio I+D, C\/ Poeta Mariano Esquillor S\/N Zaragoza 50018 Spain"},{"name":"Health Research Institute Aragon (IIS Aragon)  Zaragoza 50009 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1493915"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01867-1"},{"key":"e_1_2_8_3_1","unstructured":"Centers for Disease Control and Prevention (CDC).More People in the United States Dying from Antibiotic\u2010Resistant Infections than Previously Estimated CDC Online Newsroom 2019.https:\/\/archive.cdc.gov\/#\/details?url=https:\/\/www.cdc.gov\/media\/releases\/2019\/p1113\u2010antibiotic\u2010resistant.html(accessed: December 2021)."},{"key":"e_1_2_8_4_1","volume":"115","author":"Klein E. 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