A biomimetic nanoplatform boosting efferocytosis via dual-pathway regulation for atherosclerosis therapy and imaging.

Abstract

Atherosclerosis remains a leading contributor to cardiovascular mortality, driven primarily by defective efferocytosis and subsequent inflammatory within vulnerable plaques. Conventional therapeutic approaches often lack the specificity to simultaneously promote clearance of apoptotic cells and modulate pro-inflammatory signaling. In this study, we presented a biomimetic nanoplatform that enhances efferocytosis through dual-pathway regulation. This platform co-delivers phosphatidylserine (PS) to provide an "eat me" signal and InVivoMAb anti-mouse CD47 (aCD47) to block the "don't eat me" pathway. Constructed on a fluorescent silica nanosphere core camouflaged with immune cell membranes, this system enables precise targeting of atherosclerotic lesions. In vitro experiments confirmed the platform significantly enhanced macrophage phagocytosis (by 265%) and attenuated inflammatory responses, while exhibiting no detectable cytotoxicity. In vivo evaluation in an atherosclerotic mouse model demonstrated significant attenuation of plaque progression and increased plaque stability. Our findings underscore the potential of this dual-signal-modulating nanoplatform as a theranostic strategy for atherosclerosis that offers synchronized therapeutic and imaging capabilities.