Cu Single-Atom Embedded g-C3N4 nanosheets Rehabilitate Multidrug-Resistant Bacteria Infected Diabetic Wounds via Photoswitchable Cascade Reaction

Cu Single-Atom Embedded g-C3N4 nanosheets Rehabilitate Multidrug-Resistant Bacteria Infected Diabetic Wounds via Photoswitchable Cascade Reaction | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Cu Single-Atom Embedded g-C 3 N 4 nanosheets Rehabilitate Multidrug-Resistant Bacteria Infected Diabetic Wounds via Photoswitchable Cascade Reaction Peng Li, Xichen Sun, Pengqi Zhu, Liuyan Tang, Pengfei Wang, Ningning Li, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5916168/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Oct, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract To tackle elevated blood glucose, multidrug-resistant (MDR) bacterial infections, and persistent inflammation in diabetic wounds, we present a therapeutic strategy that employs a photoswitch-controlled catalytic cascade reaction, utilizing a photocatalytic material engineered through the synergistic regulation of nitrogen vacancies and single-atom embedding. The nitrogen vacancies in g-C3N4 promise the photocatalytic glucose oxidation to H2O2 and facilitate its subsequent conversion into hydroxyl radicals (•OH) through a photocatalytic cascade reaction with Cu single-atom embedded g-C3N4 nanosheets (Cu/CN). Concurrently, the •OH and superoxide anions (•O2⁻) are obtained by photocatalytic water splitting over Cu/CN. Over 99.9% antibacterial activity and effective biofilm inhibition are achieved via photocatalytic cascade reaction. In the dark, excess ROS are scavenged by Cu/CN, reducing inflammation of wounds and promoting polarization of M2 macrophages. This photoswitchable cascade reaction effectively treated MDR bacterial-infected diabetic wounds, highlighting its potential for antibiotic-free diabetic wound therapy and its promising prospects for clinical applications. Biological sciences/Microbiology/Bacteria/Bacterial techniques and applications Biological sciences/Microbiology/Biofilms Physical sciences/Chemistry/Photochemistry/Photocatalysis nitrogen vacancy graphitic carbon nitride photocatalytic antibacterial chronic wound infections antibiofilm Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupportingInformation.pdf Supporting Information Cite Share Download PDF Status: Published Journal Publication published 16 Oct, 2025 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5916168","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":416765191,"identity":"24837e19-5119-46a1-bf12-19ed418c69ca","order_by":0,"name":"Peng Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYBACNhDxwMAGmUuMlgSDNBK0gEECw2EStPCxn057kFBwPs/gdo8Bw4eywwz8sxsIOIwnd7tBgsHtYoM7ZwwYZ5w7zCBx5wABLQy52ySAWhK33cgxYOZtO8xgIJFAQAv/W5CWcxAtf4nSIgG25QBECyNxWt6C/JKcuP/OsYKDPefSeSRuENAi35+77cGHP3aJM2c3b3zwo8xajn8GAS0M8LiQYGA4AKR4CKpH0TIKRsEoGAWjACsAAP5kQ1WQjnf/AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-5876-2177","institution":"Northwestern Polytechnical University","correspondingAuthor":true,"prefix":"","firstName":"Peng","middleName":"","lastName":"Li","suffix":""},{"id":416765192,"identity":"c5bd5644-c74a-47cb-b491-da53496f2634","order_by":1,"name":"Xichen Sun","email":"","orcid":"","institution":"Northwestern Polytechnical University","correspondingAuthor":false,"prefix":"","firstName":"Xichen","middleName":"","lastName":"Sun","suffix":""},{"id":416765193,"identity":"5fcd0738-d84f-4c02-9e26-f2995f19b62f","order_by":2,"name":"Pengqi Zhu","email":"","orcid":"","institution":"Shanxi Bethune Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pengqi","middleName":"","lastName":"Zhu","suffix":""},{"id":416765194,"identity":"686e43d9-84dc-404e-b2d8-00db69706024","order_by":3,"name":"Liuyan Tang","email":"","orcid":"","institution":"Northwestern Polytechnical University","correspondingAuthor":false,"prefix":"","firstName":"Liuyan","middleName":"","lastName":"Tang","suffix":""},{"id":416765195,"identity":"c02baa2f-ccda-46d7-bd02-008f17b1e7ca","order_by":4,"name":"Pengfei Wang","email":"","orcid":"","institution":"Northwestern Polytechnical University","correspondingAuthor":false,"prefix":"","firstName":"Pengfei","middleName":"","lastName":"Wang","suffix":""},{"id":416765196,"identity":"a0dd5253-0e85-4739-87b4-f597beb8cc8a","order_by":5,"name":"Ningning Li","email":"","orcid":"","institution":"Northwestern Polytechnical University","correspondingAuthor":false,"prefix":"","firstName":"Ningning","middleName":"","lastName":"Li","suffix":""},{"id":416765197,"identity":"cfee27bc-5a42-4452-9c9c-ba4cef9052f9","order_by":6,"name":"Qing Wang","email":"","orcid":"","institution":"Northwestern Polytechnical University","correspondingAuthor":false,"prefix":"","firstName":"Qing","middleName":"","lastName":"Wang","suffix":""},{"id":416765198,"identity":"2338f4cb-6910-441b-8242-322ee5d3c7a3","order_by":7,"name":"Yan-Ru Lou","email":"","orcid":"https://orcid.org/0000-0001-7717-6010","institution":"University of Helsinki","correspondingAuthor":false,"prefix":"","firstName":"Yan-Ru","middleName":"","lastName":"Lou","suffix":""},{"id":416765199,"identity":"64c7f85a-0567-440a-b56f-0eb83999ed64","order_by":8,"name":"Yuezhou Zhang","email":"","orcid":"https://orcid.org/0000-0002-8560-5716","institution":"Northwestern Polytechnical University","correspondingAuthor":false,"prefix":"","firstName":"Yuezhou","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-01-28 05:15:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5916168/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5916168/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41467-025-64242-z","type":"published","date":"2025-10-16T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":93747437,"identity":"cf81aee9-7b60-497a-a468-7ef218706063","added_by":"auto","created_at":"2025-10-17 07:05:49","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2515013,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5916168/v1_covered_60589067-506e-4203-8291-e238ef38ea77.pdf"},{"id":76633461,"identity":"9f02607f-341b-4675-a060-cdc611713994","added_by":"auto","created_at":"2025-02-19 07:07:30","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":1338475,"visible":true,"origin":"","legend":"Supporting Information","description":"","filename":"SupportingInformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5916168/v1/51343a17d2aebeffedfc9dee.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"\u003cp\u003eCu Single-Atom Embedded g-C\u003csub\u003e3\u003c/sub\u003eN\u003csub\u003e4\u003c/sub\u003e nanosheets Rehabilitate Multidrug-Resistant Bacteria Infected Diabetic Wounds via Photoswitchable Cascade Reaction\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"nitrogen vacancy, graphitic carbon nitride, photocatalytic antibacterial, chronic wound infections, antibiofilm","lastPublishedDoi":"10.21203/rs.3.rs-5916168/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5916168/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"To tackle elevated blood glucose, multidrug-resistant (MDR) bacterial infections, and persistent inflammation in diabetic wounds, we present a therapeutic strategy that employs a photoswitch-controlled catalytic cascade reaction, utilizing a photocatalytic material engineered through the synergistic regulation of nitrogen vacancies and single-atom embedding. The nitrogen vacancies in g-C3N4 promise the photocatalytic glucose oxidation to H2O2 and facilitate its subsequent conversion into hydroxyl radicals (•OH) through a photocatalytic cascade reaction with Cu single-atom embedded g-C3N4 nanosheets (Cu/CN). Concurrently, the •OH and superoxide anions (•O2⁻) are obtained by photocatalytic water splitting over Cu/CN. Over 99.9% antibacterial activity and effective biofilm inhibition are achieved via photocatalytic cascade reaction. In the dark, excess ROS are scavenged by Cu/CN, reducing inflammation of wounds and promoting polarization of M2 macrophages. This photoswitchable cascade reaction effectively treated MDR bacterial-infected diabetic wounds, highlighting its potential for antibiotic-free diabetic wound therapy and its promising prospects for clinical applications.","manuscriptTitle":"Cu Single-Atom Embedded g-C3N4 nanosheets Rehabilitate Multidrug-Resistant Bacteria Infected Diabetic Wounds via Photoswitchable Cascade Reaction","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-19 07:07:25","doi":"10.21203/rs.3.rs-5916168/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b3fbf1ec-5a99-49fb-af9a-907de7495e01","owner":[],"postedDate":"February 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":44549367,"name":"Biological sciences/Microbiology/Bacteria/Bacterial techniques and applications"},{"id":44549368,"name":"Biological sciences/Microbiology/Biofilms"},{"id":44549369,"name":"Physical sciences/Chemistry/Photochemistry/Photocatalysis"}],"tags":[],"updatedAt":"2025-10-17T07:05:41+00:00","versionOfRecord":{"articleIdentity":"rs-5916168","link":"https://doi.org/10.1038/s41467-025-64242-z","journal":{"identity":"nature-communications","isVorOnly":false,"title":"Nature Communications"},"publishedOn":"2025-10-16 04:00:00","publishedOnDateReadable":"October 16th, 2025"},"versionCreatedAt":"2025-02-19 07:07:25","video":"","vorDoi":"10.1038/s41467-025-64242-z","vorDoiUrl":"https://doi.org/10.1038/s41467-025-64242-z","workflowStages":[]},"version":"v1","identity":"rs-5916168","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5916168","identity":"rs-5916168","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}