Abstract 11474: Ti 3 C 2 T x MXene Nanosheets for Immunomodulation and Prevention of Allograft Vasculopathy

Abstract

Allograft vasculopathy is an aggressive form of accelerated atherosclerosis that manifests uniquely in transplanted hearts, lungs and kidneys. Activated blood vessel endothelial cells (ECs) stimulate alloreactive CD4 + and CD8 + T-lymphocytes to result in sustained inflammation. MXenes, an emerging class of transition metal carbides, have recently been shown to have unique immunomodulatory properties that may be leveraged to treat allograft vasculopathy. In this study, we present the synthesis, characterization and application of novel two-dimensional titanium carbide MXene (Ti 3 C 2 T x ) nanosheets for immunomodulation. MXene nanosheets (MNSs) were selectively etched from bulky Ti 3 AlC 2 MAX phase using hydrofluoric acid. The resultant MNSs are 2 to 5 μm in size and are surface modified with carboxyl, hydroxyl and amine functional groups for biological interactions. Using an in vitro co-culture system, we found that MNSs interact with activated human ECs to reduce activation and pro-inflammatory Th1 polarization of allogeneic CD4 + lymphocytes. Mechanistically, we showed that treatment with MNSs significantly decreased expression of the co-stimulatory molecule CD86 and altered the ratio of endothelial surface co-stimulatory to co-inhibitory molecules. Furthermore, when applied in an in vivo rat model of allograft vasculopathy, treatment with MNSs reduced lymphocyte infiltration and preserved medial smooth muscle cell integrity within transplanted vessel segments. Taken together, these findings suggest that these novel MNSs have potential as an effective treatment to prevent allograft vasculopathy.