Researchers developed a nanomedicine that delivers luteolin precisely to plaques, boosting fat clearance and improving artery stability
Atherosclerosis is driven by plaque buildup and foam cell formation in arteries. Researchers developed a luteolin-based nanomedicine designed for precise delivery and traceless release under plaque conditions. The therapy enhances lipid efflux in foam cells, reducing plaque size and improving stability. Preclinical studies show this approach could offer a targeted and effective strategy for treating atherosclerosis and lowering the risk of serious cardiovascular events.
Atherosclerosis—the buildup of fatty plaques inside arteries—is the underlying cause of heart attacks and strokes, claiming millions of lives each year. While drugs such as statins have helped reduce cholesterol and improve outcomes, current treatments do not directly target the cellular drivers of plaque formation and instability. Researchers have long sought strategies that can act precisely at the disease site, removing excess fat from arterial walls and stabilizing vulnerable plaques.
The study
published in Research on July 11, 2025, was led by Prof. He Huang from the Department of Cardiology at Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China. It also included Prof. Boxuan Ma from the same department and Prof. Lingbo Qian from the School of Basic Medical Sciences and Forensic Medicine at Hangzhou Medical College, China. The researchers report the creation of a novel luteolin nanomedicine designed to do just that. Luteolin, a plant-derived flavonoid found in fruits and vegetables, is known for its anti-inflammatory and vascular protective properties. However, its therapeutic potential has been hampered by poor solubility, low bioavailability, and the risk of cytotoxicity. The new nanomedicine overcomes these limitations through a clever design: nanoparticles assembled entirely from luteolin molecules that disintegrate only under the unique conditions of diseased plaques, such as oxidative stress and acidity.
“Traditional luteolin therapies are limited by poor solubility and bioavailability,” explains Dr. Huang.
“Our nanomedicine overcomes these barriers by ensuring that luteolin reaches the plaque site in its most active form, without the safety concerns associated with carrier-based nanoparticles.”
The research team engineered the nanoparticles to recognize CD44, a receptor abundant on foam cells—the lipid-laden macrophages and smooth muscle cells that are central to plaque progression. Once bound, the nanoparticles broke apart and released luteolin directly inside diseased tissue. In laboratory experiments, the nanomedicine suppressed foam cell formation and activated lipid transport proteins that promoted cholesterol efflux, essentially clearing out excess fat from the cells. Genetic analyses revealed upregulation of key regulators of lipid metabolism, including ABCA1 and ABCG1, confirming the treatment’s direct effect on cholesterol removal pathways.
Animal experiments provided further proof of the nanomedicine’s power. In mice prone to develop atherosclerosis, treatment with the luteolin nanoparticles significantly reduced plaque size and lipid burden. The plaques also became structurally more stable, with smaller necrotic cores, stronger collagen scaffolding, and lower levels of enzymes linked to plaque rupture. In addition, the treatment reduced infiltration of inflammatory macrophages, helping create a healthier arterial environment. Compared to free luteolin or non-targeted nanoparticles, the designed system showed superior accumulation in atherosclerotic lesions and produced stronger therapeutic effects, without signs of acute toxicity.
“The results were striking,” says Dr. Ma.
“Not only did the nanomedicine inhibit plaques, it also made them more stable—reducing the risk of rupture, which is the main trigger of heart attacks and strokes.”
By combining a natural compound with advanced nanotechnology, this study opens the door to a new class of cardiovascular therapeutics. Unlike many nanomedicines that rely on additional carriers, the luteolin system is carrier-free, reducing the risk of side effects from foreign materials. Its stimulus-responsive, “traceless release” design ensures that the drug is only activated at the disease site, maximizing efficacy and safety.
“This is a pioneering step,” adds Dr. Qian.
“By combining active targeting with traceless release, we can maximize therapeutic benefit while minimizing risks. It’s an approach that could be extended beyond atherosclerosis to other diseases characterized by oxidative stress and inflammation.”
Although the study was conducted in mice, the findings provide strong proof of concept for human application. With cardiovascular disease continuing to rise globally, innovative therapies that go beyond conventional cholesterol-lowering drugs are urgently needed. Overall, the luteolin nanomedicine offers a potential new weapon to not only reduce plaque but also make it less dangerous, addressing both the burden and the threat of atherosclerosis.
The complete study is accessible via DOI: 10.34133/research.0754