An MSR1‐Targeting Glycolipid Platform for Imaging the Changes of Phagocytic Macrophages in the Progression of Atherosclerotic Plaque

The progression of atherosclerosis (AS) plaque is marked by a shift in the main cell component of phagocytic macrophages from myeloid‐derived to vascular smooth muscle cell (VSMCs)‐derived macrophages. It remains a great challenge to identify proper targeting markers and to image the changes of phagocytic macrophage, including myeloid‐derived or VSMCs‐derived macrophages. Herein, we propose macrophage scavenger receptor 1 (MSR1), as a detection marker of dynamic phagocytic macrophage changes in atherosclerotic plaques. To focus on this macrophage marker, we designed an MSR1‐targeting synthetic glycolipid platform called sulfated L‐fucopyranoside glycolipid (SFGL) SFGL is precisely fabricated based on a specially designed synthetic glycolipid with a well‐defined structure, and it can be further co‐assembled with functional components such as organic fluorescent molecules and inorganic gold nanoparticles to achieve multifunctionality. The study revealed the main cell component change of phagocytic macrophages from zsGreen positive (zsGreen + ) myeloid‐derived MSR1 (hi) macrophages to tdTomato positive (tdTomato + ) VSMCs‐derived MSR1 (hi) macrophages during AS progression in VSMCs lineage tracing atherosclerotic mice. This change indicates the progression of atherosclerotic plaque, as observed using Near‐Infrared (NIR) imaging and micro‐computed tomography (micro‐CT). Based on the results, SFGL, with its exceptional targeting ability and convenient functionalization, is a promising candidate for both basic macrophage‐tracking research and applications such as imaging and drug delivery.