Last Updated on August 8, 2026 by Staff
Fatty plaques in the arteries are usually treated as a cholesterol problem: lower the cholesterol, lower the danger.
A new treatment shrank those plaques in mice while their cholesterol stayed the same. It worked on the immune cells inside the artery wall instead.
How plaques turn dangerous
Plaques build up when fatty material collects inside an artery wall. Over time the immune system responds, and cells called macrophages gather there. These cells are supposed to clear away debris, including cells that have died.
That cleanup job has a name: efferocytosis. In advanced plaques the macrophages often turn strongly inflammatory and lose some of their ability to do it.
Dead cells then pile up, and the buildup becomes a soft, damaged center called a necrotic core, which makes a plaque more likely to rupture.
A carrier built to find plaques
The core of the treatment is a stack of ultra-thin sheets made from black phosphorus.
Each flat sheet ran about 150 nanometers across, several hundred times narrower than a human hair, and about nine nanometers thick. On their own they would drift through the bloodstream with no particular destination.
So the researchers added a short peptide as a molecular address. It sticks to collagen IV, a structural protein that shows up in larger amounts in inflamed plaques. Then they loaded the sheets with Resolvin D1, a molecule the body uses to help resolve inflammation.
The address worked. In mice, the targeted particles collected in the main artery about 4.3 times more than particles without it. Of the targeted particles found there, about 76 percent had been taken up by plaque macrophages, against 41 percent for the untargeted version.
The cells changed how they behaved
Inside the plaque, a macrophage can settle into a strongly inflammatory state or a calmer, less damaging one. After treatment, more of the cells shifted toward the calmer state.
The treated cells also changed the signals they released. They put out less of three inflammatory molecules, including TNF-alpha and IL-6, and more of a calming one, IL-10.
The cleanup machinery shifted too. The cells made more of a protein called MerTK, which helps a macrophage grab and swallow a dying cell, and less of one that normally blocks that job.
The treated cells also changed how they made energy, leaning more on oxygen-based production and on burning fat. The researchers tied both shifts to better cleanup.
Plaques shrank in the sickest mice
The main test used mice fed a high-fat diet for 12 weeks, long enough to build advanced plaques. The researchers then treated them twice a week for another 12 weeks, comparing the full treatment against saline, the drug alone, and the empty targeted particles.
In the saline group, plaques covered about 32 percent of the main artery. With the drug alone, that fell to 21 percent, and with the empty particles, to 18 percent. With the full treatment, it fell to 9 percent.
The changes inside the animals matched the ones seen in the dish. In treated mice, plaque macrophages leaned toward the calmer state and carried fewer inflammatory signals. Under the microscope, more dead cells were caught in the act of being cleared.
The same pattern held at a second site, the root of the aorta near the heart. The plaques there also looked more stable. Their necrotic cores were smaller, and the collagen cap over each plaque, the part that keeps it from bursting, was thicker.
The cholesterol results are the surprise
In the fully treated mice, HDL, total cholesterol, and LDL were no different from the untreated group. Whatever shrank the plaques, it was not lower blood cholesterol.
The treatment also appeared safe over the 12 weeks. The researchers saw no obvious organ damage and no meaningful change in body weight or several blood measures across the groups.
None of this means the treatment will work in people. Everything happened in mice, and the researchers note that small animals reproduce only part of human artery disease.
The plan next is larger animals, including pigs with induced atherosclerosis, to track where the particles travel and whether they stay safe. Human trials would come only after that.
Journal: Acta Pharmaceutica Sinica B
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