Using Nanoparticles to Combat Arteriosclerosis

In industrialized countries, a particularly high number of people suffer from arteriosclerosis — with fatal consequences: Deposits in the arteries lead to strokes and heart attacks. A team of researchers under the leadership of the University of Bonn has now developed a method for guiding replacement cells to diseased vascular segments using nanoparticles. The scientists demonstrated in mice that the fresh cells actually exert their curative effect in these segments. However, much research remains to be done prior to use in humans. The results are now being published in the journal ACS NANO.

In arteriosclerosis, pathological deposits form in the arteries and this leads to vascular stenosis. Strokes and heart attacks are a frequent outcome due to the resultant insufficient blood flow. Endothelial cells that line the blood vessels play an important role here.

“They produce nitric oxide and also regulate the expansion of the vessels and the blood pressure,” explains Dr. med. Daniela Wenzel, junior professor from the Institute of Physiology I of the University of Bonn, adding that damage to endothelial cells is usually the first step in developing arteriosclerosis.

Dr. Med. Wenzel and colleagues were able to regenerate damaged endothelial cells, and they successfully tested their approach in mice. The scientists transferred the eNOS gene into cultured cells with the aid of viruses. This enzyme stimulates nitric oxide production in the endothelium. “[eNOS] is an essential precondition for the full restoration of the original function of the endothelial cells,” reports Dr. Sarah Vosen from Dr. med. Wenzel’s team.

Together with the gene, the researchers also introduced nanoparticles with an iron core. “The iron changes the properties of the endothelial cells; they become magnetic,” points out Dr. Sarah Rieck from the Institute of Physiology I of the University of Bonn. The nanoparticles ensure that the endothelial cells equipped with the eNOS gene can be delivered using a magnet to the desired site in the blood vessels where they can then exert their curative effect.

The scientists tested this combination method in mice whose carotid artery endothelial cells were injured. They injected the replacement cells into the artery and were able to position them at the correct site using the magnet.

“After half an hour, the endothelial cells adhered so securely to the vascular wall that they could no longer be flushed away by the bloodstream,” says Dr. Med. Wenzel.

The researchers then removed the magnets and tested whether the fresh cells had fully regained their function. They found that the new endothelial cells produced nitric oxide and thus expanded the vessel, as is usual in the case of healthy arteries. “The mouse woke up from the anesthesia and ate and drank normally,” notes Dr. Med. Wenzel.

Normally, doctors surgically remove vascular deposits from the carotid artery and in some cases place a stent to correct the bottleneck in the crucial blood supply. “However, these areas frequently become blocked with deposits once again,” says Dr. Med. Wenzel. “In contrast, we are getting to the root of the problem and are restoring the original condition of healthy endothelial cells.”

The researchers hope that what works in mice is also possible in humans and stress that there is a considerable need for more research.