Tandem Effect Of Decursin And Enzalutamide Co-Delivered By Elastin Nanogel In Prostate Cancer Xenografts

Tandem Effect Of Decursin And Enzalutamide Co-Delivered By Elastin Nanogel In Prostate Cancer Xenografts | 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 Tandem Effect Of Decursin And Enzalutamide Co-Delivered By Elastin Nanogel In Prostate Cancer Xenografts Jonathan Yeshwanth Daniel, Gulzar Ahmed Rather, R Siva, K. Natarajan, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9057482/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 Prostate cancer frequently develops resistance to androgen receptor-targeted therapies such as enzalutamide, underscoring the need for rational combination strategies that exploit complementary mechanisms while improving delivery and tolerability. Here, we investigated the tandem therapeutic potential of decursin—a natural coumarin with documented anti-proliferative, anti-androgenic, and pathway-modulating effects in prostate cancer—co-delivered with enzalutamide via a biocompatible elastin-based nanogel. In silico predictions using ProTox and STITCH confirmed favorable toxicity profiles and minimal adverse interaction risks for the combination, supporting its preclinical advancement. In vivo toxicity assessments in zebrafish embryos and Sprague-Dawley rats revealed negligible systemic toxicity at therapeutic doses, with only mild, reversible, dose-dependent liver function perturbations at higher exposures. The core efficacy evaluation utilized DU145 human prostate cancer cells, a well-established model of aggressive, androgen-independent disease in athymic nude mouse xenografts. The elastin nanogel-co-loaded formulation elicited a considerable reduction in tumor volume and burden compared to free drugs or monotherapy controls, demonstrating clear tandem synergy and superior anti-tumor activity. These findings highlight the elastin nanogel as an effective platform for overcoming enzalutamide resistance through synergistic pathway targeting, offering a promising translational strategy for castration-resistant prostate cancer with an excellent safety margin. Biological sciences/Cancer Biological sciences/Drug discovery Health sciences/Oncology Prostate cancer Elastin Castration resistance Xenograft Zebrafish Global oncology Full Text Additional Declarations No competing interests reported. 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-9057482","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":610100929,"identity":"7454ee05-5b8d-418c-9fd4-7f36cc05e155","order_by":0,"name":"Jonathan Yeshwanth Daniel","email":"","orcid":"","institution":"Sri Ramachandra Institute of Higher Education \u0026 Research","correspondingAuthor":false,"prefix":"","firstName":"Jonathan","middleName":"Yeshwanth","lastName":"Daniel","suffix":""},{"id":610100930,"identity":"a668e796-6f9f-4162-9ab6-443923f79612","order_by":1,"name":"Gulzar Ahmed Rather","email":"","orcid":"","institution":"Sri Ramachandra Institute of Higher Education \u0026 Research","correspondingAuthor":false,"prefix":"","firstName":"Gulzar","middleName":"Ahmed","lastName":"Rather","suffix":""},{"id":610100931,"identity":"c256878c-61de-41a9-897e-d9df50c5c8ce","order_by":2,"name":"R Siva","email":"","orcid":"","institution":"Sri Ramachandra Institute of Higher Education \u0026 Research","correspondingAuthor":false,"prefix":"","firstName":"R","middleName":"","lastName":"Siva","suffix":""},{"id":610100932,"identity":"76521b41-1bf8-4f70-82ad-9950d77ab0cf","order_by":3,"name":"K. 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