Percutaneous transluminal angioplasty is a common procedure to clear blocked arteries. This is often accomplished by inserting a balloon catheter. At the site of the blockage the balloon is inflated and pushes against the arterial wall for a few minutes before being removed. In many cases this is sufficient to open the artery. However, the balloon often damages the arterial wall and it is important that the endothelium repairs itself quickly in order to prevent blood clots and excessive proliferation of smooth muscle (hyperplasia). A common method to stimulate endothelial growth is to introduce vascular endothelial growth factor (VEGF) locally or through the bloodstream. Unfortunately, the half-life of VEGF is short and the large amount needed for efficacy is expensive. This motivated researchers from the Harbin Medical University in the Heilongjiang Province of China to develop a way to locally deliver the VEGF gene to the site of a ballon-injured artery.
The team fabricated magnetic DNA-gelatin microspheres composed of iron oxide nanospheres crosslinked with gelatin and VEGF plasmids. The gelatin stabilizes the VEGF cDNA. The plasmid produces the VEGF protein at the site, and its presence induces nearby cells to produce VEGF protein. The microspheres were delivered to the injured artery in a rabbit leg by a catheter, and maintained at that location for 7 days with two arc magnets placed outside of the injured leg. This method succeeded in stimulating local VEGF expression and attenuated hyperplasia at the site. Histological analysis of the injured site 1 to 4 weeks after implantation of the microspheres indicated increased VEGF expression. Additionally, blood serum levels of VEGF remained undetectable, and there were no abnormal changes in the blood or major organs of the animals, indicating local targeting of the microspheres and biological safety.
The synthesis of magnetic microspheres for site-specific delivery of genetic material has potential in future treatment methods for a variety of diseases. This work demonstrates that it can be successful with a combination of local mechanical placement and maintenance of that location by an external magnetic field. It is also important to note that genetic material can be stably delivered by this system. Previous attempts at gene transfer to such sites were not specific enough or the genetic material wasn't stable long enough to elicit satisfactory expression.
This research, entitled “Magnetic nanosphere-guided site-specific delivery of vascular endothelial growth factor gene attenuates restenosis in rabbit balloon-injured artery” was published in the Journal of Vascular Surgery online on January 13, 2015. doi:10.1016/j.jvs.2014.11.068
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