Astaxanthin and Dihydroartemisinin loaded PLGA NPs for atherosclerosis therapy via regulating lipid metabolism and immune microenvironment

The active ingredients of Traditional Chinese Medicine with diverse structures exhibited anti-inflammatory and lipid lowering functions, demonstrating significant therapeutic effects in inflammatory diseases of atherosclerosis. We incorporate Astaxanthin (AST) and Dihydroartemisinin (DHA) into PLGA NPs to synthesized HA@PLGA@AST/DHA NPs (HPAD NPs) for alleviating atherosclerosis. In vitro assay indicated that the designed HPAD NPs promoted cholesterol efflux of macrophages by enhancing selective lipophagy, which is benefit to lipid antigen degradation. Meanwhile, HPAD NPs regulated T-cell differentiation and crucially induced macrophages from pro-inflammatory M1 type to anti-inflammatory M2 type. In vivo study demonstrated that HPAD NPs decreased the necrotic core dimension and improved plaque stability in ApoE -/- mice with atherosclerosis. Overall, this research indicated the promise of HPAD NPs for the targeted therapy of atherosclerosis. Graphical abstract Schematic illustration of HPAD NPs preparation and therapeutic strategy for AS. (A) Preparation of HPAD NPs. (B) HPAD NPs reduce inflammation and prevent AS by restoring lipophagy of macrophages and promote the polarization from M1 type to M2 type to modulate the AIM.