Abstract 15705: Immunomodulatory Titanium Carbide MXene Nanosheets for Treatment of Cardiac Allograft Vasculopathy

Abstract

Introduction: Cardiac allograft vasculopathy is an aggressive form of atherosclerosis and a major cause of mortality among patients with heart transplants. Blood vessel endothelial cells stimulate alloreactive T-lymphocytes to result in sustained inflammation. MXenes are an emerging class of nanomaterials that have been shown to possess immunomodulatory properties. Herein, we report the first application of titanium carbide (Ti 3 C 2 T x ) MXene nanosheets for prevention of allograft vasculopathy. Methods and Results: Detailed physicochemical characterization of Ti 3 C 2 T x MXene nanosheets was performed using scanning/transmission electron microscopy, x-ray diffraction, and x-ray photoelectron spectroscopy. Ti 3 C 2 T x MXene nanosheets were 2 to 5 μm in size and enriched with biologically active surface groups. In vitro , MXene nanosheets interacted with human umbilical vein endothelial cells (HUVECs) and downregulated the expression of genes involved in alloantigen presentation through the class I major histocompatibility complex (IRF1, TAP1, B2M), and reduced the activation and pro-inflammatory polarization of co-cultured allogeneic lymphocytes. Consequently, RNA-Seq analysis of these lymphocytes showed that treatment with MXene nanosheets downregulated genes responsible for transplant-induced T-cell activation, cell-mediated rejection, and development of allograft vasculopathy. Furthermore, gene set enrichment analysis revealed significant negative enrichment of genes involved in interferon alpha/beta and interferon gamma signaling. Finally, in an in vivo rat model of allograft vasculopathy, treatment with Ti 3 C 2 T x MXene nanosheets reduced lymphocyte infiltration and preserved medial smooth muscle cell integrity within transplanted aortic allografts. Conclusion: These findings support the potential of Ti 3 C 2 T x MXene nanosheets for prevention and treatment of allograft vasculopathy and other inflammatory diseases. This research also opens the door to development of Ti 3 C 2 T x MXene technologies for other immune-sensitive regenerative medicine applications.