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[The Scientist] Fake blood 2.0?
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2009-12-16
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Fake blood 2.0?
 
Posted by Bob Grant
[Entry posted at 14th December 2009]

 
Newly created synthetic particles that mimic red blood cells may one day carry drug molecules and/or oxygen through bloodstreams, according to researchers writing in this week's issue of the Proceedings of the National Academy of Sciences (PNAS).

What's more, the team of scientists in Michigan and California say the particles could also be used to improve the resolution of magnetic resonance imaging.
The synthetic red blood cells
that Mitragotri and his team developed

Image: Nishit Doshi


"It's a very nice paper and very exciting work," Krishnendo Roy, a biomedical engineer at the University of Texas at Austin who wasn't involved with the study, told The Scientist. "The beauty of their method is its simplicity."

University of California, Santa Barbara, chemical engineer Samir Mitragotri led the team of scientists and told The Scientist that the blood cell-like particles could evolve into useful tools in the clinic. "What we got very excited about was making a structure with synthetic materials that begins to mimic a natural object," said Mitragotri. "If we can bridge the gap [between synthetic materials and living cells] it will open up tremendous opportunities for synthetic materials."

Mitragotri said that he and his team tested the ability of the particles to carry oxygen, finding that they had a "comparable" oxygen-carrying capacity to actual red blood cells. He added that it may be possible in the future to link therapeutic agents destined for the vascular system, such as heparin, to the particles so that they can be easily distributed throughout the blood. The artificial blood cells, with attached iron oxide nanoparticles, could also one day improve MRI resolution by serving as contrast agents that provide a different imaging signal compared to the surrounding tissue, Mitragotri said.

Mitragotri and his colleagues created the artificial red blood cells by first making tiny spheres out of a biodegradable polymer called poly(lactic acid-co-glycolide) (PLGA). They then exposed the spheres to isopropanol, which collapsed them into the discoid shape characteristic of red blood cells. The researchers then layered proteins -- either albumin or hemoglobin -- onto the doughnut-shaped disks, cross-linked the proteins to give them extra strength and stability, and finally dissolved away the PLGA template to leave only a strong but flexible shell of proteins in the shape and size (about 7 microns in diameter) of a red blood cell.

Mitragotri and his team then tested the ability of the artificial cells to behave like real blood cells, passing them through glass capillary tubes that were narrower than the diameter of the particles and testing their oxygen-carrying capacity. They showed that the particles could carry about 90 percent of the oxygen real red blood cells can carry. They also showed that a drug-mimicking molecule could easily be loaded into and off of the artificial blood cells.

"They conclusively demonstrated some stuff concerning oxygen-carrying capacity and the potential for drug release," Patrick Doyle, a chemical engineer at the Massachusetts Institute of Technology who was not involved with the study, told The Scientist.

But years of continued testing lie between Mitragotri's synthetic red blood cells and clinical application. Several questions, including how long the particles will remain in circulation, how the immune system will react to the synthetic blood cells, and how efficiently they transport oxygen, remain to be answered. Mitragotri said that his lab plans on answering these questions by studying the particles in model organisms, research that is set to begin soon.

"Whether this is applicable in an in vivo setting," said Roy, "we won't know that for 3, 4, or 5 years."

"I don't think these [clinical applications] are far off ideas, but you have to go through all the usual regulatory hurdles," said Doyle, noting that the synthetic cells might also be used to study how cellular aberrations, such as tumor cells, behave in the body. "Ultimately they can also be model systems, by which you can understand disease states of cells," he added.