Dynamic Cross-Linked Injectable Hydrogel for Synergistic Oxaliplatin– Resveratrol Therapy in Colorectal Cancer Peritoneal Metastasis

Dynamic Cross-Linked Injectable Hydrogel for Synergistic Oxaliplatin– Resveratrol Therapy in Colorectal Cancer Peritoneal Metastasis | 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 Method Article Dynamic Cross-Linked Injectable Hydrogel for Synergistic Oxaliplatin– Resveratrol Therapy in Colorectal Cancer Peritoneal Metastasis Haonan Huang, Haoyu Huang, Cheng Zuo, Jing Yang, Huizi Li, Fan Jiang, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9029520/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Peritoneal metastasis (PM) of colorectal cancer (CRC) remains a major therapeutic challenge due to the limited efficacy of current systemic and intraperitoneal treatments. To overcome these limitations, we developed an injectable, self-healing hydrogel constructed from a dual dynamic cross-linked network formed by borate ester and Schiff base bonds between phenylboronic acid-modified carboxymethyl chitosan (CMCS-PBA) and oxidized dextran (ODEX). This hydrogel was engineered for sustained intraperitoneal co-delivery of oxaliplatin (OXA) and resveratrol-loaded mesoporous silica nanoparticles (MSNs@RES). The system exhibited excellent biocompatibility and significantly inhibited cancer cell proliferation, migration, and invasion while inducing apoptosis and immunogenic cell death (ICD) in vitro. In a murine model of CRC peritoneal metastasis, the dual-drug-loaded hydrogel markedly suppressed tumor progression, reduced ascites formation, and prolonged survival. Proteomic analysis further revealed that treatment significantly modulated key signaling pathways, including HIF-1α-mediated angiogenesis, apoptosis-related cascades, and TGF-β-driven epithelial–mesenchymal transition (EMT). Collectively, this work presents a rationally designed localized delivery platform with significant potential for the treatment of colorectal cancer peritoneal metastasis. Injectable hydrogel Colorectal peritoneal metastasis Mesoporous silica nanoparticles Oxaliplatin Resveratrol Full Text Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterials.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 10 May, 2026 Reviewers agreed at journal 01 May, 2026 Reviewers agreed at journal 29 Apr, 2026 Reviewers invited by journal 20 Mar, 2026 Editor assigned by journal 11 Mar, 2026 Submission checks completed at journal 11 Mar, 2026 First submitted to journal 04 Mar, 2026 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-9029520","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Method Article","associatedPublications":[],"authors":[{"id":609240192,"identity":"40947ac6-f3c5-428a-9590-a60179907abe","order_by":0,"name":"Haonan Huang","email":"","orcid":"","institution":"Second Affiliated Hospital of Nanchang University","correspondingAuthor":false,"prefix":"","firstName":"Haonan","middleName":"","lastName":"Huang","suffix":""},{"id":609240193,"identity":"6d72f755-9d90-49e4-aa19-84ea3fbb2705","order_by":1,"name":"Haoyu Huang","email":"","orcid":"","institution":"Second Affiliated Hospital of Nanchang 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To overcome these limitations, we developed an injectable, self-healing hydrogel constructed from a dual dynamic cross-linked network formed by borate ester and Schiff base bonds between phenylboronic acid-modified carboxymethyl chitosan (CMCS-PBA) and oxidized dextran (ODEX).\u003c/p\u003e \u003cp\u003eThis hydrogel was engineered for sustained intraperitoneal co-delivery of oxaliplatin (OXA) and resveratrol-loaded mesoporous silica nanoparticles (MSNs@RES). The system exhibited excellent biocompatibility and significantly inhibited cancer cell proliferation, migration, and invasion while inducing apoptosis and immunogenic cell death (ICD) in vitro.\u003c/p\u003e \u003cp\u003eIn a murine model of CRC peritoneal metastasis, the dual-drug-loaded hydrogel markedly suppressed tumor progression, reduced ascites formation, and prolonged survival. 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