Release date: 2017-06-15
Image source: Meddagdet
Vascular endothelial cells are a barrier from the blood to the tissue in the blood. Usually, it allows small molecules of drugs to enter the tissue from the blood, but for macromolecules and drug-carrying magnetic nanoparticles, unless leakage occurs, They are unable to cross the vascular barrier, and many drug delivery strategies are now only available for the treatment of solid tumors.
If it can achieve effective control of the opening of the vascular endothelium, it is very beneficial for local administration, and it can be very helpful for the treatment of cancer and other diseases. Researchers from Rice University have tried to achieve artificial control of vascular endothelial permeability in vivo through magnetism, aiming to deliver drugs to target areas through strong magnets, reaching tissues and organs that are currently difficult to reach. The study was published recently. Nature's issue "Nature Communications".
The researchers prepared a batch of iron oxide nanoparticles (MNP) for experiments. They found that MNPs, together with strong magnets, can be used to open gaps in drug delivery between vascular line endothelial cells. Image source: Rice University
VE-cadherin is a key component of tight junctions between vascular endothelial cells, anchored to the actin cytoskeleton of vascular endothelial cells, and this tight association between VE-cadherin and F-actin Can synergistically control the function of the vascular endothelium. In the past few years, many scientists have tried extensive research using magnetic nanoparticles (MNPs) to guide drug delivery. As a nanoscale magnet, it can be endocytosed by cells within a certain size without affecting cell viability. MNP regulates intracellular F-actin, which alters the tight junctions between vascular endothelial cells and increases endothelial permeability through the effects of F-actin.
Researchers are preparing nanoparticles between 16 and 33 nanometers in diameter to target endothelial cells. Once the particles enter the cell, they can be manipulated with a magnet. Image source: Rice University
The researchers first established a microfluidic model of vascular endothelial cells by culturing real vascular endothelial cells through a microfluidic device. MNPs with a diameter of 16-33 nm were injected into the microfluidic device and labeled with fluorescence. VE-cadherin was stained to observe its performance. When an external magnetic field is applied, the distribution of VE-cadherin becomes discontinuous and diffuses, indicating that the adhesion between cells is disrupted.
If this damage is permanent, there is no doubt that this method is not safe. Interestingly, when the external magnetic field was withdrawn for 12 hours, actin fibers and VE-cadherin recovered to their original distribution. Microfluidic experiments have shown that the application of MNP and external magnetic force can cause reversible changes in the actin cytoskeleton, and the disruption of interendothelial connections caused by this change is temporary and does not permanently alter endothelial function. For in vivo experiments, this is a good prerequisite for safety.
The researchers then experimented with in vivo experiments using the tail vein of athymic nude mice as a model. Due to the depth of blood vessels in the body, the researchers used a strong magnetic field and a MNP of 33 nm in diameter. Vascular permeability assessment was performed by detecting circulating indocyanine green (ICG), which was measured by observing the accumulation of ICG at the tail vein. The experiment was carried out under conditions of anesthesia in mice. After MNP was injected into the body, the tail of the mouse was placed in a magnetic field for 2 hours. Under exposure to a magnetic field, the ICG is injected through the tail vein and detects the distribution in the body. The experiment found that ICG signals were significantly enhanced in the tail vein of mice with magnetic fields. In control mice without a magnetic field, MNP had no effect on the distribution of ICG.
The results indicate that external magnetic properties can induce MNP to reversibly alter the vascular endothelial permeability of target tissues, which will have great potential application value for the treatment of tissues and diseases targeted for avascular leakage.
Reference material
[1] Magnetic forces enable controlled drugdelivery by disrupting endothelial cell-cell junctions
[2] Magnets and Nanoparticles for On-DemandLeaky Vessels
[3] Making vessels leaky on demand couldaid drug delivery
Source: Health New Vision (Micro Signal HealthHorizon)
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