Active Chemical Messenger-Driven Immune Activation via Electrochemical Patch for <i>In-Situ</i> Tumor Vaccination.

Abstract

Chemical messengers with critical signaling roles hold significant potential as therapeutic agents for disease treatment. However, their therapeutic efficacy is limited by the lack of effective platforms for precise dosage control. Herein, taking hypochlorous acid (HClO) as a model chemical messenger, a wearable bioelectronic patch (e-patch) capable of electrocatalytically generating HClO to activate immunity for <i>in situ</i> tumor vaccination is designed. The e-patch utilizes Co₃O₄ nanowires as electrocatalysts for chlorine evolution reaction (CER), producing HClO at an applied voltage of 2.0 V (vs. Ag/AgCl). Additionally, an electroosmotic flow (EOF) mechanism integrated into the microneedle array enhances the transdermal delivery efficiency of HClO into tumors. The dosage and frequency of e-vaccination can be intelligently controlled via a wirelessly operated mobile device. Under the regulation of HClO, tumor cells undergo pyroptosis, exposing tumor-associated antigens. Moreover, HClO can successfully induce the repolarization of tumor-associated macrophages and enhance the antigen-presenting capacity of dendritic cells, thereby demonstrating the immunoadjuvant effect as a proinflammatory chemical messenger. By using the e-patch for vaccination, T lymphocyte-mediated antitumor immunity is effectively activated, leading to the eradication of tumor metastasis and relapse. This immuno-electronic patch provides a paradigm for the intelligent control of chemical messenger-based biomedicine.