Targeting Nanoplatform for Atherosclerosis Inhibition and Degradation via a Dual-Track Reverse Cholesterol Transport...

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.