Room-temperature-stable immunosuppressive nanovesicles for mitigating immunopathology and streamlining cardioprotection post-infarction

Abstract

To understand the role of T lymphocytes during myocardial infarction (MI) progression, public single-cell sequencing data from infarcted murine hearts were re-analyzed, identifying highly heterogeneous T lymphocytes and hyper-activated clusters of proliferative CD8 cytotoxic T lymphocytes. Conventional secretome-based extracellular vesicle therapies often suffer from poor stability and lack of cost-effectiveness. In response, room-temperature-stable, membrane-based nanovesicles enriched with programmed cell death-ligand 1 (PD-L1@NV) have been developed to mitigate T cell-initiated ischemic hyperinflammation. Functionally, PD-L1@NV effectively binds to T cell membranes, suppressing their proliferation and inducing exhaustion in activated CD8 T lymphocytes, thereby supporting myocardial tissue recovery. Mechanistically, PD-L1@NV diminishes CD8 cytotoxic T lymphocyte abundance and augments regulatory T cell population, reshaping in vivo T cell dynamics. The development of room-temperature-stable PD-L1@NV presents a straightforward, scalable, and secure strategy for MI treatment, focusing particularly on addressing T cell-driven immunopathology.