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Ischemic heart disease, especially myocardial infarction (MI), is one of the leading causes of mortality worldwide. The resulting myocardial fibrosis significantly impairs cardiac function and further aggravates heart failure. Despite extensive efforts, effective therapeutic interventions still struggle to reverse myocardial fibrosis and restore cardiac function. The latest research highlights the crucial role of metabolic reprogramming in the activation of cardiac fibroblasts (CF) and their transformation into myofibroblast-like cells (driving fibrosis). Gastrodin (GAS) is a phenolic glycoside derived from Gastrodia elata, which has shown promising anti-fibrotic and metabolic regulatory effects; however, its clinical application is limited by poor pharmacokinetic properties and the lack of targeted delivery. In this study, we designed a nanocomposite hydrogel for intrapericardial injection, incorporating FAP-targeted CAR-T cell membrane-coated GAS nanoparticles (FAP-CAR T CM@PPA-G NPs) into a pH/ROS responsive CP/PCPD hydrogel. This innovative system enables specific targeting of FAP-positive myofibroblast-like cells, allowing for the on-demand release of GAS triggered by pathological ROS and pH changes, and effectively inhibiting fibrosis by regulating the KLF2/CREB5/HIF-1α/PFKFB3 metabolic axis. Our findings not only provide a novel therapeutic platform for fibrosis treatment after myocardial infarction but also elucidate the mechanism underlying the anti-fibrotic effect of GAS. This strategy holds great potential for advancing the clinical translation of GAS-based therapy in myocardial fibrosis and heart failure. This study was published in Bioactive Materials under the title "FAP-targeted gastrodin nanoparticles in responsive hydrogel alleviate cardiac fibrosis through fibroblast metabolic reprogramming".
Reference Information:
DOI: 10.1016/j.bioactmat.2026.02.052
