Luteolin Nanomedicine with Stimulus-Driven Traceless Release for Targeting Treatment of Atherosclerosis by Enhancing Lipid Efflux

Atherosclerotic plaques pose a substantial risk for life-threatening cardiovascular complications due to their propensity to trigger acute clinical events. Foam cell formation, resulting from dysregulated lipid homeostasis, serves as a pivotal pathological hallmark in the progression of atherosclerosis. In this study, we presented a precision therapeutic strategy targeting foam cells of multiple origins. The carrier-free nanomedicine Dlut based on luteolin was constructed, featuring CD44 active targeting and stimulus-driven traceless release. Dlut demonstrated active foam cell targeting capability and complete disintegration triggered by oxidative stress and acidic microenvironment, enabling a traceless release of luteolin. Transcriptomic profiling revealed that Dlut inhibited foam cell formation by accelerating lipid efflux. In vivo studies further demonstrated that Dlut significantly reduced plaque burden and improved plaque stability, highlighting a translational potential of atherosclerosis.