Cell-Selective Modulation of Mechanotransduction using CD44-Mediated Nanocarriers to Reverse Cardiac Fibrosis

Gloria Garofollo – Researcher, Centro Cardiologico Monzino; Jose Inácio – Researcher, NOVA Medical School, Universida de NOVA de Lisboa; Rebecca Dutton – technician, Stem Cells and Development Lab, Universida de NOVA de Lisboa; Josè Belo – Prof, Stem Cells and Development Lab, Universida de NOVA de Lisboa; Henrique Girao – Prof, Faculty of Medicine, University of Coimbra; Maurizio Pesce – Prof, Centro Cardiologico Monzino; Angel Raya – Prof, Regenerative Medicine Program, Institut d'Investigació Biomèdica de Bellvitge; Ida Genta – Prof, Department of Drug Sciences, University of Pavia

Introduction: This study investigates a targeted approach to treat myocardial fibrosis by interfering cellular mechanotransduction. We aim to modulate the Hippo pathway specifically in cardiac fibroblasts (CFs) and macrophages (ICs) without affecting cardiomyocytes (CMs). While CF mechanosensing promotes fibrosis, Hippo signalling is vital for CM survival post-injury [1]. Our strategy exploits hyaluronic acid (HA)-functionalized nanoparticles to deliver Verteporfin (VP) or siRNA. By targeting the CD44 receptor, highly expressed in CFs but not CMs, these HA-NPs ensure localized, cell-selective therapeutic delivery.