Monocyte Differentiation‐Surveilling Nano‐Shuttles for Activatable Targeted Inhibition of Atherosclerotic Plaque Progression

Abstract

Atherosclerosis can form intimal plaques in the arteries and undergo plaque rupture with followed stroke or myocardial infarction under certain pathological conditions. However, suboptimal intraplaque accumulation, along with severe off‐target effects, remain formidable obstacles for efficient pharmacotherapy of atherosclerosis. A characteristic feature of the progression of atherosclerosis is the continuous recruitment of inflammatory monocytes that differentiate into foamy macrophages with the generation of legumain in the plaques. In this study, a bio‐activatable nano‐shuttle based on human serum albumin is conceived that contained curcumin to allow the precise inhibition of atherosclerosis progression. Following intravenous injection, the nano‐shuttles are almost exclusively engulfed by inflammatory monocytes in an efferocytosis‐mimetic manner and selectively co‐migrated with the monocytes towards the plaques. The nano‐shuttles are readily activated to release the initially arrested curcumin in response to the generation of legumain upon the differentiation of monocytes into foamy macrophages within the plaques. Treatment assessments on atheroprone apolipoprotein‐E‐deficient mice indicated that the nano‐shuttles substantially inhibit the progression of atherosclerosis by attenuating the plaque inflammation burden without any obvious adverse effects. The integration of highly selective accumulation and specific drug activation of the nano‐shuttles in plaques can arouse an advanced therapeutic strategy to prevent atherosclerotic cardiovascular disease.

Advances in the treatment of atherosclerosis with ligand‐modified nanocarriers

“…[24] Targeting the inhibition of monocyte recruitment is regarded as a promising therapeutic objective due to its potential to prevent the subsequent accumulation and proliferation of macrophages within the plaque. [25] Additionally, it can aid in averting the destabilization and rupture of the atherosclerotic plaque. [26] The administration of antibodies blocking VCAM-1 or ICAM-1 inhibits inflammatory monocyte recruitment during acute inflammation.…”