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Although there have been advancements in the treatment of atherosclerosis, the effectiveness in reversing vulnerable atherosclerotic plaques is limited and remains a major challenge in translational cardiovascular research. We have developed OPN-HMCN@MLT, a targeted nanoplatform that combines melatonin (MLT) with osteopontin-binding peptides (OPN) and hyaluronic acid-modified pores. By taking advantage of the acidic environment, excessive expression of HAase, and OPN enrichment in susceptible plaques, this system can continuously trigger a cascade of drug release through OPN recognition, HA degradation, and acidic pH. This system achieves precise plaque localization and untagged photoacoustic imaging (PA), leveraging the inherent imaging ability of the carbon carrier while enhancing the biological activity of MLT. The increased OPN expression in foam cells helps OPN-HMCN@MLT selectively retain in vulnerable plaques, thereby enhancing the PA signal related to the plaques. In vivo studies have shown that OPN-HMCN@MLT not only inhibits plaque progression but also promotes the regression of existing lesions, accompanied by a reduction in foam cell accumulation, improved lipid metabolism reprogramming, and enhanced plaque stability, with no detectable systemic toxicity. By functionally combining targeted lipid restoration with supportive molecular imaging at the pathological substrate level, this study establishes a treatment-centered nanomedicine strategy for precise intervention and longitudinal monitoring, providing strong translational potential for the management of advanced atherosclerosis. This study was published in Bioactive Materials under the title "A foam cell-targeted lipophagy restoration strategy stabilizes vulnerable atherosclerotic plaques".
Reference Information: DOI: 10.1016/j.bioactmat.2026.02.041
