Drug-caged drug: photoredox catalysis-enabled dual decaging of nitric oxide and local anesthetics for simultaneous antibacterial treatment and pain relief

Drug-caged drug: photoredox catalysis-enabled dual decaging of nitric oxide and local anesthetics for simultaneous antibacterial treatment and pain relief | 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 Drug-caged drug: photoredox catalysis-enabled dual decaging of nitric oxide and local anesthetics for simultaneous antibacterial treatment and pain relief Jinming Hu, Jiqian Zhang, Guihai Gan, Chenchen Cao, Shaoqiu Zheng, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5302737/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 16 Feb, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Bacterial infections often result in significant pain, negatively impacting patient outcomes and quality of life. Conventional therapies primarily focus on pathogen eradication but frequently overlook the associated pain, thereby limiting their overall clinical effectiveness. Herein, we propose a 'drug-caged drug' strategy in which the secondary amine group of the local anesthetic tetracaine (TTC) is selectively caged by nitric oxide (NO), forming the TTC-NO prodrug. The TTC-NO prodrug is co-loaded with the photocatalyst fac-Ir(ppy)3 into poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) micellar nanoparticles (TTC-NO@M), enabling dual uncaging of TTC and NO under mild visible light irradiation through a photocatalytic mechanism. We demonstrate that TTC-NO@M exhibits combined antibacterial, anti-inflammatory, and analgesic activities by simultaneously releasing NO and TTC. This strategy effectively treats MRSA-infected mice in both cutaneous wound and septic arthritis models while alleviating infection-associated pain. This work offers a promising approach to address the dual challenges of bacterial infections and the associated pain. Physical sciences/Materials science/Biomaterials/Biomedical materials Physical sciences/Chemistry/Photochemistry/Photocatalysis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupportingInformation.pdf Cite Share Download PDF Status: Published Journal Publication published 16 Feb, 2026 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. 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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-5302737","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":372769335,"identity":"0facce70-2282-42ba-8e0b-2b6c28f0ea8b","order_by":0,"name":"Jinming 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