An antioxidant nanozyme for targeted cardiac fibrosis therapy post myocardial infarction

An antioxidant nanozyme for targeted cardiac fibrosis therapy post myocardial infarction | 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 Research Article An antioxidant nanozyme for targeted cardiac fibrosis therapy post myocardial infarction Ziyi Gu, Xueliang Liu, Zhen Qi, Zhou Fang, Yiting Jiang, Yuting Huang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4794111/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Dec, 2024 Read the published version in Journal of Nanobiotechnology → Version 1 posted 11 You are reading this latest preprint version Abstract The excessive release of reactive oxygen species (ROS) after myocardial infarction (MI) disrupts the natural healing process, leading to cardiac fibrosis and compromising patient prognosis. However, the clinical application of many antioxidant drugs for MI treatment is hindered by their poor antioxidant efficacy and inability to specifically target the heart. Here we developed a tannic acid-modified MnO 2 nanozyme (named MnO 2 @TA), which can achieve cardiac targeting to inhibit post-MI fibrosis and enhance cardiac function. Specifically, the MnO 2 @TA nanozyme, endowed with superoxide dismutase (SOD) and catalase (CAT) activities, effectively scavenges ROS, suppressing fibroblast activation and mitigating cardiac fibrosis without affecting cardiac repair. Notably, the incorporation of TA improves the nanozyme's affinity for the elastin and collagen-rich extracellular matrix in cardiac tissues, significantly increasing its retention and uptake within the heart and thereby enhancing its anti-fibrotic efficacy. In a murine myocardial infarction model, MnO 2 @TA demonstrates remarkable cardiac protection, significantly improving cardiac function while attenuating cardiac fibrosis. This study presents a valuable reference for clinical research aimed at inhibiting cardiac fibrosis and advancing myocardial infarction treatments. Cardiac fibrosis Myoardial infarction Nanozyme Heart-targeted Full Text Additional Declarations No competing interests reported. Supplementary Files GuZYMnO2TAforfibrosistherapySI.docx Cite Share Download PDF Status: Published Journal Publication published 18 Dec, 2024 Read the published version in Journal of Nanobiotechnology → Version 1 posted Editorial decision: Revision requested 22 Sep, 2024 Reviews received at journal 18 Sep, 2024 Reviews received at journal 17 Sep, 2024 Reviewers agreed at journal 10 Sep, 2024 Reviews received at journal 09 Sep, 2024 Reviewers agreed at journal 08 Sep, 2024 Reviewers agreed at journal 08 Sep, 2024 Reviewers invited by journal 08 Sep, 2024 Editor assigned by journal 01 Aug, 2024 Submission checks completed at journal 01 Aug, 2024 First submitted to journal 24 Jul, 2024 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-4794111","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":344217271,"identity":"1d3dbd96-e599-4d63-a77d-aeb47096daf1","order_by":0,"name":"Ziyi Gu","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Ziyi","middleName":"","lastName":"Gu","suffix":""},{"id":344217272,"identity":"565cc2c4-9a41-403b-8635-d389cd59b501","order_by":1,"name":"Xueliang Liu","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Xueliang","middleName":"","lastName":"Liu","suffix":""},{"id":344217274,"identity":"36253d00-ed47-4981-a286-f183ee88c0d2","order_by":2,"name":"Zhen Qi","email":"","orcid":"","institution":"Central South University","correspondingAuthor":false,"prefix":"","firstName":"Zhen","middleName":"","lastName":"Qi","suffix":""},{"id":344217275,"identity":"517f9f05-91b9-4c23-8658-25906299a634","order_by":3,"name":"Zhou Fang","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Zhou","middleName":"","lastName":"Fang","suffix":""},{"id":344217276,"identity":"1e7227ad-3155-4d1f-ae05-6d73d1a8586a","order_by":4,"name":"Yiting Jiang","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Yiting","middleName":"","lastName":"Jiang","suffix":""},{"id":344217277,"identity":"e15e39bf-3987-489b-a1da-3b724428d5be","order_by":5,"name":"Yuting Huang","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Yuting","middleName":"","lastName":"Huang","suffix":""},{"id":344217279,"identity":"4b55472b-58ab-4ac7-a981-033102712c2e","order_by":6,"name":"Yongyi Wang","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Yongyi","middleName":"","lastName":"Wang","suffix":""},{"id":344217280,"identity":"ca7dbf82-4a33-476c-884b-960b04e52360","order_by":7,"name":"Lianming Wu","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Lianming","middleName":"","lastName":"Wu","suffix":""},{"id":344217283,"identity":"7594e6c1-4b35-4ac3-9ad2-d7887693a289","order_by":8,"name":"Yu Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0UlEQVRIiWNgGAWjYPACGwYDCIOZaC1ppGs5TIIWgxs5hp8Lfp23N+c/nSbBUGGd2MB+9gAhLcbSM/tuJ+6ckbtNguFMemIDT14CIS0G0rw9txMMbvBuk2BsO5zYIMFjQNCW37w95+wNzp8FavlHnBYzaZ4fBxg3HAA6jLGBCC2SZ56VWfM2JCduuJG72SLhWLpxG08Ofi18x5M33+b5Ywdy2MYbH2qsZfvZz+DXonCAw4CBsQ3KSwBiNrzqgUC+gf0BA8MfQspGwSgYBaNgRAMAcPxI+TfIcdsAAAAASUVORK5CYII=","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":true,"prefix":"","firstName":"Yu","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2024-07-24 09:26:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4794111/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4794111/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12951-024-03047-6","type":"published","date":"2024-12-18T15:58:08+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":72201929,"identity":"50a5a96a-c17b-4e43-b9d8-5bf7a6188be3","added_by":"auto","created_at":"2024-12-23 16:12:20","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1552275,"visible":true,"origin":"","legend":"","description":"","filename":"GuZYMnO2TAforfibrosistherapyresearch2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4794111/v1_covered_49b4c63a-b4e3-4764-b9f3-a89d8dd80f25.pdf"},{"id":63473489,"identity":"aa1789d7-3b92-4ab4-bcf2-f1f8cf033d69","added_by":"auto","created_at":"2024-08-28 13:49:12","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2143966,"visible":true,"origin":"","legend":"","description":"","filename":"GuZYMnO2TAforfibrosistherapySI.docx","url":"https://assets-eu.researchsquare.com/files/rs-4794111/v1/86231273815e927ad6c741dc.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"An antioxidant nanozyme for targeted cardiac fibrosis therapy post myocardial infarction","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"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":"journal-of-nanobiotechnology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jnan","sideBox":"Learn more about [Journal of Nanobiotechnology](http://jnanobiotechnology.biomedcentral.com)","snPcode":"12951","submissionUrl":"https://submission.nature.com/new-submission/12951/3","title":"Journal of Nanobiotechnology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cardiac fibrosis, Myoardial infarction, Nanozyme, Heart-targeted","lastPublishedDoi":"10.21203/rs.3.rs-4794111/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4794111/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe excessive release of reactive oxygen species (ROS) after myocardial infarction (MI) disrupts the natural healing process, leading to cardiac fibrosis and compromising patient prognosis. However, the clinical application of many antioxidant drugs for MI treatment is hindered by their poor antioxidant efficacy and inability to specifically target the heart. Here we developed a tannic acid-modified MnO\u003csub\u003e2\u003c/sub\u003e nanozyme (named MnO\u003csub\u003e2\u003c/sub\u003e@TA), which can achieve cardiac targeting to inhibit post-MI fibrosis and enhance cardiac function. Specifically, the MnO\u003csub\u003e2\u003c/sub\u003e@TA nanozyme, endowed with superoxide dismutase (SOD) and catalase (CAT) activities, effectively scavenges ROS, suppressing fibroblast activation and mitigating cardiac fibrosis without affecting cardiac repair. Notably, the incorporation of TA improves the nanozyme's affinity for the elastin and collagen-rich extracellular matrix in cardiac tissues, significantly increasing its retention and uptake within the heart and thereby enhancing its anti-fibrotic efficacy. In a murine myocardial infarction model, MnO\u003csub\u003e2\u003c/sub\u003e@TA demonstrates remarkable cardiac protection, significantly improving cardiac function while attenuating cardiac fibrosis. This study presents a valuable reference for clinical research aimed at inhibiting cardiac fibrosis and advancing myocardial infarction treatments.\u003c/p\u003e","manuscriptTitle":"An antioxidant nanozyme for targeted cardiac fibrosis therapy post myocardial infarction","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-28 13:49:07","doi":"10.21203/rs.3.rs-4794111/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-22T05:42:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-18T14:10:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-18T01:36:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"76040872856783034861565789675551653268","date":"2024-09-10T13:06:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-09T07:13:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7048884627138013807731981779999163393","date":"2024-09-09T00:40:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"282277101831006387444975815211775213663","date":"2024-09-08T14:31:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-08T12:08:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-01T15:56:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-01T15:56:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Nanobiotechnology","date":"2024-07-24T09:24:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-nanobiotechnology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jnan","sideBox":"Learn more about [Journal of Nanobiotechnology](http://jnanobiotechnology.biomedcentral.com)","snPcode":"12951","submissionUrl":"https://submission.nature.com/new-submission/12951/3","title":"Journal of Nanobiotechnology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4aa792ae-d118-4259-8d53-fed479180855","owner":[],"postedDate":"August 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-12-23T16:04:23+00:00","versionOfRecord":{"articleIdentity":"rs-4794111","link":"https://doi.org/10.1186/s12951-024-03047-6","journal":{"identity":"journal-of-nanobiotechnology","isVorOnly":false,"title":"Journal of Nanobiotechnology"},"publishedOn":"2024-12-18 15:58:08","publishedOnDateReadable":"December 18th, 2024"},"versionCreatedAt":"2024-08-28 13:49:07","video":"","vorDoi":"10.1186/s12951-024-03047-6","vorDoiUrl":"https://doi.org/10.1186/s12951-024-03047-6","workflowStages":[]},"version":"v1","identity":"rs-4794111","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4794111","identity":"rs-4794111","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}