Scavenger receptor-AI targeted theranostic nanoparticles for regression of atherosclerotic plaques via ABCA1 modulation.

ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in atherosclerotic formation through mediated cholesterol efflux in macrophage-derived foam cells. In this study, a scavenger receptors AI (SR-AI) targeted theranostic nanoparticles was constructed for atherosclerosis regression via ABCA1 activation in foam cells. ABCA1-upregulator 5242331 and IR780 were encapsulated in PLGA-PEG micelles which were conjugated with SR-AI targeting peptide (PP1) to formulate the nanoparticles (SAU-NPs). Immunostaining revealed that SR-AI was highly expressed both in macrophage foam cells and in atherosclerotic plaque of ApoE-/- mice. The SAU-NPs have shown more active targeting to plaque lesion with higher stability compared with non-SR-AI targeted nanoparticles. The transformation from macrophage to foam cells was inhibited by SAU-NPs carried 5242331. Cholesterol deposition was effectively reduced in foam cells by SAU-NPs through activating the LXRα-ABCA1/ABCG1/SR-BI pathway. In conclusion, theranostic SAU-NPs which carried ABCA1-upregulator 5242331 exert beneficial effects on atherosclerosis regression via LXRα activation.