A novel targeted angiogenesis technique using VEGF conjugated magnetic nanoparticles and in-vitro endothelial barrier crossing

Abstract

Background: Vascular endothelial growth factor is well known for its angiogenesis potential. The study was performed to determine the possible pro-angiogenic role of magnetic nanoparticles coupled to VEGF in vitro and their capacity to cross an endothelial monolayer. This novel treatment technique for angiogenesis could be potentially useful for therapeutic purposes using magnetic nanoparticles. Methods: Magnetic nanoparticles (MN) were synthesized and were conjugated with the vascular endothelial growth factor. The particles were tested in vitro in a 2D to 3D culture system. MN was seeded in different positions in relation to an HUVEC spheroid to assess a preferential migration. To evaluate the MN capacity to cross the endothelial barrier, a confluent monolayer of HUVEC cells was seeded on top of a collagen gel. MN was placed in dissolution on the cell culture media, and the MN position was determined by confocal microscopy for 24 h. Results: HUVEC spheroids were able to generate a preferential sprouting depending on the MN position. Meanwhile, there was random migration when the MN's were placed all over the collagen gel and no sprouting when no MN was added. The trans-endothelial migration capacity of the MN was observed after 20 h in culture in the absence of external stimuli. Conclusion: Here we show in vitro angiogenesis following the distribution of the MN conjugated with growth factors. These nanoparticles could be controlled with a magnet to place them in the ischemic area of interest and speed up vascular recovery. Also, MN has potentials to cross endothelium, opening the doors to a possible intravascular and extravascular treatment.