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In this study, we prepared a resveratrol\u2010derived antimicrobial conjugated oligoelectrolyte (COE) named\n                    <jats:bold>DY6<\/jats:bold>\n                    to enhance drug\u2010like properties. While\n                    <jats:bold>DY6<\/jats:bold>\n                    \u2019s increased hydrophobicity augmented its antibacterial efficacy, it also induced significant cytotoxicity, highlighting the long\u2010existing dilemma of amphiphilic antimicrobials. To mitigate this issue, we employed a supramolecular strategy by complexing\n                    <jats:bold>DY6<\/jats:bold>\n                    with sodium sulfobutyl ether \u03b2\u2010cyclodextrin (\n                    <jats:bold>S\u03b2CD<\/jats:bold>\n                    ), forming the host\u2013guest inclusion complex\n                    <jats:bold>DY6@S\u03b2CD<\/jats:bold>\n                    . This complex elevated the half\u2010maximal inhibitory concentration (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) against L929 cells from 9.4 to over 128\u00a0\u00b5g mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    while maintaining a minimum inhibitory concentration (MIC) of 2\u00a0\u00b5g mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    against methicillin\u2010resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA). NMR and UV\u2013vis spectroscopic analyses confirmed that\n                    <jats:bold>DY6<\/jats:bold>\n                    \u2019s aromatic backbone is encapsulated within the hydrophobic cavity of\n                    <jats:bold>S\u03b2CD<\/jats:bold>\n                    . Isothermal titration calorimetry revealed that size compatibility and electrostatic interactions are essential for stable complex formation and enhanced biocompatibility. Importantly,\n                    <jats:bold>DY6@S\u03b2CD<\/jats:bold>\n                    exhibited no resistance development over 14\u2010day serial passages against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    , significantly outperforming norfloxacin. In biofilm\u2010based MRSA\u2010infected wound and corneal models,\n                    <jats:bold>DY6@S\u03b2CD<\/jats:bold>\n                    more effectively reduced bacterial load and inflammation compared to the last\u2010resort antibiotic vancomycin. These findings demonstrate the potential utility of supramolecular host\u2013guest approach based on COEs to overcome the drug\u2010resistant challenges.\n                  <\/jats:p>","DOI":"10.1002\/anie.202504581","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T06:25:47Z","timestamp":1747635947000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Host\u2013Guest Antimicrobial Based on Conjugated Oligoelectrolyte and Cyclodextrin"],"prefix":"10.1002","volume":"64","author":[{"given":"Pengke","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Polymer Optoelectronic Materials and Devices Guangdong Basic Research Center of Excellence for Energy &amp; Information Polymer Materials State Key Laboratory of Luminescent Materials and Devices School of Materials Science and Engineering South China University of Technology Guangzhou 510640 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Orthopedics and Traumatology Department of Orthopaedics Nanfang Hospital Southern Medical University Guangzhou 510515 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghao","family":"Yao","sequence":"additional","affiliation":[{"name":"Institute of Polymer Optoelectronic Materials and Devices Guangdong Basic Research Center of Excellence for Energy &amp; Information Polymer Materials State Key Laboratory of Luminescent Materials and Devices School of Materials Science and Engineering South China University of Technology Guangzhou 510640 P.R. China"},{"name":"School of Materials Science and Engineering South China University of Technology Guangzhou Guangdong 510640 P.R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peirong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Polymer Optoelectronic Materials and Devices Guangdong Basic Research Center of Excellence for Energy &amp; Information Polymer Materials State Key Laboratory of Luminescent Materials and Devices School of Materials Science and Engineering South China University of Technology Guangzhou 510640 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianan","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Polymer Optoelectronic Materials and Devices Guangdong Basic Research Center of Excellence for Energy &amp; Information Polymer Materials State Key Laboratory of Luminescent Materials and Devices School of Materials Science and Engineering South China University of Technology Guangzhou 510640 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Polymer Optoelectronic Materials and Devices Guangdong Basic Research Center of Excellence for Energy &amp; Information Polymer Materials State Key Laboratory of Luminescent Materials and Devices School of Materials Science and Engineering South China University of Technology Guangzhou 510640 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Yao","sequence":"additional","affiliation":[{"name":"Institute of Polymer Optoelectronic Materials and Devices Guangdong Basic Research Center of Excellence for Energy &amp; Information Polymer Materials State Key Laboratory of Luminescent Materials and Devices School of Materials Science and Engineering South China University of Technology Guangzhou 510640 P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufen","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory Medicine Center, Nanfang Hospital Southern Medical University  Guangzhou 510515 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Materials Science and Engineering South China University of Technology Guangzhou Guangdong 510640 P.R. 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