Macrophage membrane enveloped on double-locked nanoplatform with right-side-out orientation to improving precise theranostic for atherosclerosis

A right-side-out orientated self-assembly of cell membrane-camouflaged theranostic nanoplatform is crucial for ensuring their biological functionality inherited from the source cells. However, the low specificity and fluorescence background interference hampered reliable assessment of lipids content in plaques. In this work, a spontaneous right-side-out coupling-driven ROS-responsive theranostic nanoplatform has been developed to enhance accumulation within atherosclerotic plaques, target lipids imaging in plaques, reduce the interference from background fluorescence and inhibit the progression of atherosclerosis (AS). A ROS-responsive lipid-unlocked fluorescent probe is constructed, followed by loading rapamycin (RAP) for safe and efficient AS therapy. Moreover, the theranostic nanoplatform is functionalized with PS-targeted peptide for binding to phosphatidylserine located on the inner leaflet of the macrophage membrane, harvesting a right-side-out-orientated coating theranostics formulation (M-TPCR) for the reliable imaging of lipids in lipids-sufficient Hela cells, foam cells and atherosclerotic plaques while keeping in fluorescence off in lipid-deficient environments, such as M0 macrophages, M1 macrophages and blood. Most importantly, the FL signals of M-TPCR are positively correlated with lipid content across foam cells, isolated aorta or aortic root sections, confirming its reliability in indicating plaques. Hence, M-TPCR provides a powerful approach for developing the biomimetic cell membrane camouflaged nanotechnology and delivers an impressive potential on the therapeutic efficacy monitoring.