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Magnetic nanoparticles for targeted gene and cell therapy

We aim to develop novel methods for the targeted gene and cell therapy of vessels and airways using magnetic nanoparticles. Therefore, we combine genetic vectors, magnetic nanoparticels and magnetic gradient fields. This allows the radially- symmetric overexpression of genes in the resident vascular endothelium or the radially-symmetric replacement of damaged endothelial cells in the vessel under flow conditions. The effects are analyzed on the single cell level, in isometric force measurements ex vivo and in animal models in vivo. Our studies demonstrate an efficient and sustained improvement of vascular function in a mouse model of vascular injury and the successful targeted modulation of angiogenesis ex and in vivo.

The combination of lentiviral vectors (LVs) and magnetic nanoparticles (MNPs) enables radially-symmetric replacement of endothelial cells in injured vessels. Left: Schematic diagram of the experimental strategy for endothelial cell replacement in mouse aorta, endothelial cells loaded with LV/MNP complexes are retained at the vascular wall in a radially-symmetric manner by a magnetic field under flow conditions. Top right picture: eGFP+ cells (green) adhere to the inner surface of the vessel 2 days after cell replacement therapy of the A. carotis in mouse. Bottom right: Immunohistochemistry shows the overexpression of endothelial nitric oxide synthase (eNOS, red) in eGFP+ endothelial cells (green) after cell replacement therapy. (Vosen et al. Vascular repair by circumferential cell therapy using magnetic nanoparticles and tailored magnets, ACS Nano, 2016)