Non-Invasive Transabdominal Photothermal Therapy Suppresses Colorectal Cancer Recurrence and Metastasis via Microbiota-Immune Axis Modulation

Non-Invasive Transabdominal Photothermal Therapy Suppresses Colorectal Cancer Recurrence and Metastasis via Microbiota-Immune Axis Modulation | 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 Non-Invasive Transabdominal Photothermal Therapy Suppresses Colorectal Cancer Recurrence and Metastasis via Microbiota-Immune Axis Modulation Ruirui Xing, Kaiwei Chen, Yazhou Liu, Luyang Zhao, Mengqian Shi, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6493668/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Colorectal cancer (CRC) recurrence and metastasis, driven by gut microbiota dysbiosis and an immunosuppressive tumor microenvironment (TME), demand strategies that concurrently target these interconnected barriers. Here, we present orally administered photothermal nanoagents (MnBV@DPHA NPs) that synergize with non-invasive transabdominal photothermal therapy (PTT) to modulate the microbial-immune axis. By coordinating endogenous biliverdin with manganese ions, the nanoagents achieve red-shifted near-infrared (NIR) absorption (880 nm), enabling precise tumor ablation via transabdominal PTT. In orthotopic CRC models, this strategy suppressed pathogenic bacteria, enriched probiotics, and reprogrammed the TME by increasing cytotoxic CD8⁺ T cells while reducing immunosuppressive Tregs. Germ-free mice validated microbiota’s essential role in immune activation, demonstrating bidirectional crosstalk that amplified therapeutic efficacy. The approach extended survival to > 80% at 120 days, compared to > 50% mortality in controls within one month, with no systemic toxicity. By harmonizing microbiota restoration and TME remodeling, this non-invasive strategy offers a translatable paradigm to overcome CRC recurrence and metastasis. Biological sciences/Biotechnology/Biomaterials/Drug delivery Health sciences/Diseases/Cancer/Cancer therapy/Drug development Colorectal cancer Intestinal microbiota Microbial-immune axis Transabdominal photothermal therapy Oral nanoagent Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supportinginformation.pdf Cite Share Download PDF Status: Posted 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-6493668","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":447456917,"identity":"823492d9-fb03-4cfe-94df-5e5fa5eca830","order_by":0,"name":"Ruirui Xing","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtElEQVRIiWNgGAWjYJCCAwwMNjwka0kjUQsQHCZBrfnsM4aHC36dlzFnb2D88IPBLo+gFplzaQmHZ/bd5rHsOcAs2cOQXExQiwQP84HDvD23eQxuJDBIA/2V2EBYC2MDUMs5HoP7D5h/E6kFaAvPjwNAWxjYiLWFLeEwb0My0C+JbZY9BsnEaOEx/szzx87enP3w4Rs/KuwIawEDxjYGBgMGxgYQSSz4Q4riUTAKRsEoGHEAANn+N3+LAqL6AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-0603-2284","institution":"Institute of Process Engineering, Chinese Academy of Sciences (CAS)","correspondingAuthor":true,"prefix":"","firstName":"Ruirui","middleName":"","lastName":"Xing","suffix":""},{"id":447456918,"identity":"d09b04ab-7416-4e8a-9d07-24370af645ad","order_by":1,"name":"Kaiwei Chen","email":"","orcid":"","institution":"Institute of Process Engineering, Chinese Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Kaiwei","middleName":"","lastName":"Chen","suffix":""},{"id":447456919,"identity":"db9da94e-30aa-4888-b753-bcc51768294b","order_by":2,"name":"Yazhou Liu","email":"","orcid":"","institution":"Institute of Process Engineering, Chinese Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Yazhou","middleName":"","lastName":"Liu","suffix":""},{"id":447456920,"identity":"ef43c1f0-625b-4a17-9999-063b3f434877","order_by":3,"name":"Luyang Zhao","email":"","orcid":"https://orcid.org/0000-0001-5695-6763","institution":"Institute of Process Engineering, Chinese Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Luyang","middleName":"","lastName":"Zhao","suffix":""},{"id":447456921,"identity":"85b55f2b-cfe6-4583-9d1f-d88ecd73c235","order_by":4,"name":"Mengqian Shi","email":"","orcid":"","institution":"Institute of Process Engineering, Chinese Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mengqian","middleName":"","lastName":"Shi","suffix":""},{"id":447456922,"identity":"e85ebc7f-208c-4c8f-9574-d2b4a046a369","order_by":5,"name":"Huadan Xue","email":"","orcid":"","institution":"Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Huadan","middleName":"","lastName":"Xue","suffix":""},{"id":447456923,"identity":"03a14a0f-acfd-4aa0-b86c-8085f2c912f4","order_by":6,"name":"Guanghui Ma","email":"","orcid":"https://orcid.org/0000-0001-9154-5556","institution":"Institute of Process Engineering, Chinese Academy of Sciences","correspondingAuthor":false,"prefix":"","firstName":"Guanghui","middleName":"","lastName":"Ma","suffix":""},{"id":447456924,"identity":"d46e1623-3cde-4da4-a9ba-a0dc876a3e4f","order_by":7,"name":"Xuehai Yan","email":"","orcid":"https://orcid.org/0000-0002-0890-0340","institution":"Institute of Process Engineering, Chinese Academy of Sciences (CAS)","correspondingAuthor":false,"prefix":"","firstName":"Xuehai","middleName":"","lastName":"Yan","suffix":""}],"badges":[],"createdAt":"2025-04-21 07:50:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6493668/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6493668/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84507975,"identity":"269c3128-0ac8-493c-bdb4-4a44480c0761","added_by":"auto","created_at":"2025-06-12 19:28:29","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1467840,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6493668/v1_covered_ca5a8aa4-eaa9-4aec-900e-fcda471edbf7.pdf"},{"id":81346242,"identity":"7b175ce3-5840-42c2-a540-e3cb79c1a3ff","added_by":"auto","created_at":"2025-04-25 04:59:06","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":4400165,"visible":true,"origin":"","legend":"","description":"","filename":"Supportinginformation.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6493668/v1/57511caa49f44caae7809e9a.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Non-Invasive Transabdominal Photothermal Therapy Suppresses Colorectal Cancer Recurrence and Metastasis via Microbiota-Immune Axis Modulation","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Colorectal cancer, Intestinal microbiota, Microbial-immune axis, Transabdominal photothermal therapy, Oral nanoagent","lastPublishedDoi":"10.21203/rs.3.rs-6493668/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6493668/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eColorectal cancer (CRC) recurrence and metastasis, driven by gut microbiota dysbiosis and an immunosuppressive tumor microenvironment (TME), demand strategies that concurrently target these interconnected barriers. Here, we present orally administered photothermal nanoagents (MnBV@DPHA NPs) that synergize with non-invasive transabdominal photothermal therapy (PTT) to modulate the microbial-immune axis. By coordinating endogenous biliverdin with manganese ions, the nanoagents achieve red-shifted near-infrared (NIR) absorption (880 nm), enabling precise tumor ablation via transabdominal PTT. In orthotopic CRC models, this strategy suppressed pathogenic bacteria, enriched probiotics, and reprogrammed the TME by increasing cytotoxic CD8⁺ T cells while reducing immunosuppressive Tregs. Germ-free mice validated microbiota\u0026rsquo;s essential role in immune activation, demonstrating bidirectional crosstalk that amplified therapeutic efficacy. The approach extended survival to \u0026gt;\u0026thinsp;80% at 120 days, compared to \u0026gt;\u0026thinsp;50% mortality in controls within one month, with no systemic toxicity. By harmonizing microbiota restoration and TME remodeling, this non-invasive strategy offers a translatable paradigm to overcome CRC recurrence and metastasis.\u003c/p\u003e","manuscriptTitle":"Non-Invasive Transabdominal Photothermal Therapy Suppresses Colorectal Cancer Recurrence and Metastasis via Microbiota-Immune Axis Modulation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-25 04:51:00","doi":"10.21203/rs.3.rs-6493668/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"287ba408-2de3-4c10-9430-18d9ed8ab723","owner":[],"postedDate":"April 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47627654,"name":"Biological sciences/Biotechnology/Biomaterials/Drug delivery"},{"id":47627655,"name":"Health sciences/Diseases/Cancer/Cancer therapy/Drug development"}],"tags":[],"updatedAt":"2025-06-12T19:20:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-25 04:51:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6493668","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6493668","identity":"rs-6493668","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}