Targeting Nanoplatform for Atherosclerosis Inhibition and Degradation via a Dual‐Track Reverse Cholesterol Transport Strategy

Abstract As a main cause of serious cardiovascular diseases, atherosclerosis is characterized by deposited lipid and cholesterol crystals (CCs), which is considered as a great challenge to the current treatments. In this study, a dual‐track reverse cholesterol transport strategy is used to overcome the cumulative CCs in the atherosclerotic lesions via a targeting nanoplatform named as LPLCH. Endowed with the active targeting ability to the plaques, the nanoparticles can be efficiently internalized and achieve a pH‐triggered charge conversion for the escape from lysosomes. During this procedure, the liver X receptor (LXR) agonists loaded in nanoparticles are replaced by the deposited lysosomal CCs, leading to a LXR mediated up‐regulation of ATP‐binding cassette transporte ABCA1/G1 with the local CCs carrying at the same time. Thus, the cumulative CCs are removed in a dual‐track way of ABCA1/G1 mediated efflux and nanoparticle‐based carrying. The in vivo investigations indicate that LPLCH exhibits a favorable inhibition on the plaque progression and a further reversal of formed lesions when under a healthy diet. And the RNA‐sequencing suggests that the cholesterol transport also synergistically activates the anti‐inflammation effect. The dual‐track reverse cholesterol transport strategy performed by LPLCH delivers an exciting candidate for the effective inhibition and degradation of atherosclerosis.