Novel Combination of Nanotechnology and Gene Therapy Repairs Damaged Arterial Walls

Vascular disease researchers have demonstrated the possibility of using a combination of magnetic nanoparticles and virally-transported genes to repair damage and restore function in the walls of arteries following anti-arteriosclerosis treatment.

Cardiovascular disease is often caused by endothelial cell (EC) dysfunction and atherosclerotic plaque formation in sites in the arterial walls. Surgical procedures of plaque removal cause irreversible damage to the EC layer, inducing impairment of vascular function.

To repair damage to the arteries and restore normal vascular function, investigators at the University of Bonn (Germany) combined nanotechnology with gene and cell therapy.

In the January 6, 2016, online edition of the journal ACS NANO, the investigators described the development of unique magnetic nanoparticles (MNPs) linked to lentiviral vectors designed to overexpress the vasoprotective gene endothelial nitric oxide synthase (eNOS) in ECs. The resulting MNP-loaded and eNOS-overexpressing cells were magnetic, and, by using an external magnet, they could be positioned at the vascular wall in a radially symmetric fashion even under flow conditions.

The investigators demonstrated that the treated vessels displayed enhanced eNOS expression and activity. Moreover, isometric force measurements revealed that EC replacement with eNOS-overexpressing cells restored endothelial function after vascular injury in mice that had been genetically engineered to lack the eNOS gene.

"Endothelial cells which 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," said senior author Dr. Daniela Wenzel, professor of physiology at the University of Bonn. "Damage to the endothelial cells is generally the insidious onset of arteriosclerosis. However, these areas frequently become blocked with deposits once again. In contrast, we are getting to the root of the problem and are restoring the original condition of healthy endothelial cells."

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