Abstract P3064: Immunoengineered Tantalum Carbide Mxene Quantum Dots For Prevention Of Transplant Vasculopathy

Abstract

Transplant vasculopathy is an aggressive form of atherosclerosis that manifests uniquely in transplanted hearts, lungs, and kidneys. Recently, immunoengineered transition metal carbides, or MXenes, have demonstrated unique immunomodulatory properties and this can potentially be leveraged to prevent transplant vasculopathy. Here, we present the synthesis, characterization and application of novel zero-dimensional tantalum carbide (Ta 4 C 3 T x ) MXene quantum dots (MQDs) for immunomodulation. A facile hydrofluoric acid-free etching protocol was developed to synthesize zero-dimensional Ta 4 C 3 T x MQDs from Ta 4 AlC 3 MAX phase. The resultant MQDs are 3 to 7 nm in diameter and are surface modified with carboxyl, hydroxyl, and amine functional groups for biological interactions. Immunomodulation was assessed in vitro through co-cultures of human umbilical vein endothelial cells (ECs) and peripheral blood mononuclear cells. We found that MQDs interact with activated human ECs in vitro to reduce activation and pro-inflammatory Th1 polarization of allogeneic CD4 + lymphocytes. Mechanistically, we showed using quantitative PCR that treatment with MQDs significantly increased endothelial surface expression of the T-cell co-inhibitory molecule PD-L1 and decreased the co-stimulatory molecule CD86. Furthermore, exploratory bulk RNA-sequencing of co-cultured lymphocytes showed decreases in the immunologic signatures of naïve T-cells and increases in the immunologic signatures of CD25 + regulatory T-cells, suggesting activation of this suppressive T-cell population. Finally, when applied in an in vivo rat model of transplant vasculopathy, treatment with MQDs reduced lymphocyte infiltration and preserved medial smooth muscle cell integrity within transplanted aortic segments. These findings suggest that these novel MQDs have potential as an effective treatment to ameliorate transplant vasculopathy.