Iontronic Click-to-Release Enables Electrically Controlled Delivery of Drugs and Biomolecules Beyond Charge and Size Limitations

Iontronic Click-to-Release Enables Electrically Controlled Delivery of Drugs and Biomolecules Beyond Charge and Size Limitations | 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 Iontronic Click-to-Release Enables Electrically Controlled Delivery of Drugs and Biomolecules Beyond Charge and Size Limitations Johannes Bintinger, Sebastian Hecko, Marle Vleugels, Christian Bayer, and 15 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7520981/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Dynamic and programmable control of therapeutic delivery is a long-standing goal in medicine. Iontronic devices offer precise electronic control over the dosage of bioactive molecules, yet their use has been confined to charged, low-molecular-weight compounds that are electrochemically stable during transport. Here, we present a hybrid delivery platform that integrates iontronic transport with bioorthogonal click-to-release chemistry. In this system, iontronic pumps electrophoretically deliver charged tetrazines as molecular scissors that selectively react with immobilized trans-cyclooctene (TCO)-linked payloads, enabling on-demand bioorthogonal cleavage of the TCO linker and controlled release. This approach retains the electronic precision of iontronics while overcoming molecular size, charge, and stability constraints. We demonstrate tunable tetrazine delivery over several days and electronically controlled release of immobilized payloads from small bioactive molecules, such as the antimitotic agent CA-4, to the large protein bovine serum albumin. Hence, by integrating bioorthogonal click-to-release strategies, iontronic delivery is extended to biologically relevant macromolecules, providing a foundation for next-level programmable electroceutical devices. Physical sciences/Chemistry/Chemical biology/Drug delivery Physical sciences/Materials science/Materials for devices/Electronic devices Physical sciences/Chemistry/Medicinal chemistry/Drug delivery Physical sciences/Chemistry/Chemical biology/Chemical tools Full Text Additional Declarations Yes there is potential Competing Interest. IBW, TAS, MB, DTS, HM, and JB are shareholders in the small, researcher controlled intellectual property company OBOE IPR AB (oboeipr.com). OBOE IPR AB owns patents related to this research, and is a holding company for subsidiary Iontronics AB. Supplementary Files SupportingInfoBioSWITCH1FINALsubmissionclean.pdf Iontronic Click-to-Release Enables Electrically Controlled Delivery of Drugs and Biomolecules Beyond Charge and Size Limitations Cite Share Download PDF Status: Under Review 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-7520981","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":515591222,"identity":"47beb496-893f-4861-9517-877c96b3a2ca","order_by":0,"name":"Johannes 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