The Polymer Society of Korea

Abstract

Modulation of adaptive immunity represents a promising approach to prevent adverse cardiac remodeling after myocardial infarction (MI). Here, we developed a nanotherapeutic platform enabling in vivo T-cell modulation to promote a reparative immune microenvironment. Anti-CD4 antibody–conjugated lipid nanoparticles encapsulating interferon-γ siRNA (aCD4-iLNPs) were engineered to selectively target splenic CD4⁺ T cells. Systemic administration of aCD4-iLNPs achieved efficient delivery to splenic CD4⁺ T cells and shifted the Th1/Th2 balance toward an anti-inflammatory phenotype. Furthermore, enhanced recruitment of Th2 cells to the infarcted myocardium activated anti-inflammatory pathways, leading to attenuation of adverse remodeling and recovery of cardiac function within four weeks post-MI. These results demonstrate that RNA interference–based in vivo T-cell modulation is a viable immunotherapeutic strategy for post-MI cardiac repair.