2 research outputs found
Analysis of Trajectories for Targeting of Magnetic Nanoparticles in Blood Vessels
The technique of magnetic drug targeting deals with binding
drugs
or genetic material to superparamagnetic nanoparticles and accumulating
these complexes via an external magnetic field in a target region.
For a successful approach, it is necessary to know the required magnetic
setup as well as the physical properties of the complexes. With the
help of computational methods, the complex accumulation and behavior
can be predicted. We present a model for vascular targeting with a
full three-dimensional analysis of the magnetic and fluidic forces
and a subsequent evaluation of the resulting trajectories of the complexes.
These trajectories were calculated with respect to the physiological
boundary conditions, the magnetic properties of both the external
field and the particles as well as the hydrodynamics of the fluid.
We paid special regard to modeling input parameters like flow velocity
as well as the distribution functions of the hydrodynamic size and
magnetic moment of the nanoparticle complexes. We are able to estimate
the amount of complexes, as well as the spatial distribution of those
complexes. Additionally, we examine the development of the trapping
rate for multiple passages of the complexes and compare the influence
of several input parameters. Finally, we provide experimental data
of an <i>ex vivo</i> flow-loop system which serves as a
model for large vessel targeting. In this model, we achieve a deposition
of lentivirus/magnetic nanoparticle complexes in a murine aorta and
compare our simulation with the experimental results gained by a non-heme-iron
assay
Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets
Cardiovascular disease is often caused
by endothelial cell (EC)
dysfunction and atherosclerotic plaque formation at predilection sites.
Also surgical procedures of plaque removal cause irreversible damage
to the EC layer, inducing impairment of vascular function and restenosis.
In the current study we have examined a potentially curative approach
by radially symmetric re-endothelialization of vessels after their
mechanical denudation. For this purpose a combination of nanotechnology
with gene and cell therapy was applied to site-specifically re-endothelialize
and restore vascular function. We have used complexes of lentiviral
vectors and magnetic nanoparticles (MNPs) to overexpress the vasoprotective
gene endothelial nitric oxide synthase (eNOS) in ECs. The MNP-loaded
and eNOS-overexpressing cells were magnetic, and by magnetic fields
they could be positioned at the vascular wall in a radially symmetric
fashion even under flow conditions. We demonstrate 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 eNOS<sup>–/–</sup> mice <i>ex</i> and <i>in vivo</i>. Thus, the combination of MNP-based gene and cell therapy with custom-made
magnetic fields enables circumferential re-endothelialization of vessels
and improvement of vascular function