The endothelial cells that line blood vessels are loaded tightly to keep blood inside and flowing, but researchers at Rice University and their colleagues have discovered it could be possible to selectively open gaps in those obstacles just enough to let large molecules through — and after that close them again.
Grain bioengineer Gang Bao and collaborators at Emory University or college and the Georgia Institute of Technology reported using magnets to help iron-oxide nanoparticles invade endothelial cells both in the particular lab and in vivo. Then they use the same magnets to produce vessels temporarily “leaky. ”
This permeability would allow large-molecule drugs to reach target tissues, Bao mentioned. Strong magnets may be able to lead nanoparticle-infused stem cells or even drug-laden nanoparticles themselves to targeted areas, even in deeply tissues like organs that current therapies cannot achieve, he said.
The study appears in Nature Communications .
“For a lot of diseases, systemic delivery through the blood stream is the only method to deliver molecules to the site, ” Bao said. “Small molecules can penetrate the blood vessel and get to the diseased cells, but large molecules like proteins or even drug-loaded nanoparticles cannot pass the endothelium effectively unless of course it is leaky. ”
Blood vessels in cancer tumors typically have holes in the endothelial barrier, but they do close on demand like Bao and his team wish to make them do.
Along with drug molecules, Bao wants to use magnets to deliver nanoparticle-infused stem cells in order to injured tissues. “Unless you can do direct injection of originate cells, let’s say into the heart, you have to do systemic delivery in addition to no control over where they go.
“Our preliminary idea was to deliver magnetic nanoparticles into stem cellular material and then use a magnet to attract the stem tissue to a particular location, ” he said. “In doing this, we also discovered that by applying a magnetic field, we’re able to generate changes in the cell’s skeletal structure in terms of the actin electrical filament structures. ”
These structural elements provide cells their shape and help keep neighboring cells firmly compacted. “We thought if we could alter the cell-cell junction by using magnetic force, there was a possibility that we could professional the leakiness of the vessel, ” Bao said.
The lab created a microfluidic flow chamber that will mimicked the vascular system and lined its pipes with real endothelial cells. Experiments proved their speculation: When a magnetic field was applied to the nanoparticle-infused cellular material, the gaps opened. Relaxing the force allowed many gaps to close after 12 hours.
Microscopic images showed that fluorescent-tagged nanoparticles were equally distributed inside the endothelial channel when a magnetic field had not been applied. When it was, the particles redistributed, and the push they applied distorted the cytoskeleton.
In certain images, actin filaments that help give a cell the shape were observed lining up with the force. “It’s a pretty dramatic change, ” Bao said. “Once a person apply the force, given enough time, the structure from the cells changes. That leads to the opening of the cell-cell junction. ”
Bao said the magnetic push also generates a biological signal that alters the particular cytoskeletal structure. “It also contributes to the leakiness, inch he said. “We’re still trying to understand what kind of transmission we give to cells and how the individual cells are reacting. ”
While there are methods to facilitate 2 types of transport across the endothelial barrier — paracellular (between cells) and transcellular (through cells) — neither is able to target specific areas of the body. Bao said his team’s method offers a solution.
He said his team is part of an ongoing collaborative project on knee restoration with the lab of Dr . Johnny Huard, a teacher of orthopedic surgery at the University of Texas Wellness Science Center at Houston. “The problem is how to build-up therapeutic stem cells around the knee and keep them right now there, ” Bao said. “After injecting the nanoparticle-infused tissues, we want to put an array of magnets around the knee to entice them.
“But if you want to treat the heart or even liver, you’d need a pretty large device to have the needed magnetic field, ” he said. “We don’t have that will yet. To drive this to a clinical setting will be a problem. ”
Materials provided by Rice University . Note: Content material may be edited for style and length.