High-density lipoprotein-based nanoplatforms for macrophage-targeted diagnosis and therapy of atherosclerosis.

Atherosclerosis, the primary cause of cardiovascular disease, which has the highest mortality worldwide, is a chronic inflammatory disease mainly induced by excessive lipid accumulation in plaque macrophages. Lipid-laden macrophages are crucial at all stages of atherosclerotic lesion progression and are, thus, regarded as popular therapeutic targets for atherosclerosis. High-density lipoprotein (HDL), an endogenous particle with excellent atherosclerotic plaque-homing properties, is considered a potential therapeutic agent for treating atherosclerosis. Based on the excellent properties of HDL, reconstituted HDL (rHDL), with physiological functions similar to those of its natural counterparts, have been successfully prepared as therapeutics and are also recognized as a potential nanoplatform for delivering drugs or contrast agents to atherosclerotic plaques owing to their high biocompatibility, amphiphilic structure, and macrophage-targeting capability. In this review, we focus on the (a) important role of macrophages in atherosclerotic lesions, (b) biological properties of rHDL as a delivery nanoplatform in atherosclerotic diseases, and (c) multiple applications of rHDL in the diagnosis and treatment of atherosclerosis. We systematically summarize the novel applications of rHDL with unique advantages in atherosclerosis, aiming to provide specific insights and inspire additional innovative research in this field.