UNC CHAPEL HILL (US) — Particles that mimic key properties of red blood cells open the door to creating fully synthetic blood.
The research is outlined in the Jan. 10 Early Edition of the Proceedings of the National Academy of Sciences.
Using technology known as PRINT (Particle Replication in Non-wetting Templates), scientists produced very soft hydrogel particles that mimic the size, shape, and flexibility of red blood cells, allowing the particles to circulate in the body for extended periods of time.
Tests of the particles’ ability to perform functions such as transporting oxygen or carrying therapeutic drugs have not been conducted, and they do not remain in the cardiovascular system as long as real red blood cells. However, the researchers believe the findings—especially regarding flexibility—are significant because red blood cells naturally deform in order to pass through microscopic pores in organs and narrow blood vessels.
Over their 120-day lifespan, real cells gradually become stiffer and eventually are filtered out of circulation when they can no longer deform enough to pass through pores in the spleen.
Synthetic red blood cell mimics, shown releasing from an adhesive film into a drop of solvent. (Credit: Timothy Merkel and Joseph DeSimone, University of North Carolina at Chapel Hill)
Synthetic red blood cell mimics measuring 6 micrometers across pass through a 3 micrometer diameter channel in a microfludic device used to test the particles’ flexibility. The particles shown had already squeezed through about 50 such channels without losing their shape or elasticity.
Attempts to create effective red blood cell mimics have been limited because the particles tend to be quickly filtered out of circulation due to their inflexibility.
Beyond moving closer to producing fully synthetic blood, the findings could also affect approaches to treating cancer.
Cancer cells are softer than healthy cells, enabling them to lodge in different places in the body, leading to the disease’s spread. Particles loaded with cancer-fighting medicines that can remain in circulation longer may open the door to more aggressive treatment approaches.
“Creating particles for extended circulation in the blood stream has been a significant challenge in the development of drug delivery systems from the beginning,” says Joseph DeSimone, professor of chemistry at the University of North Carolina at Chapel Hill.
“Although we will have to consider particle deformability along with other parameters when we study the behavior of particles in the human body, we believe this study represents a real game changer for the future of nanomedicine.”
The ability to mimic the natural processes of a body for medicinal purposes has been a long-standing but evasive goal for researchers.
“These findings are significant since the ability to reproducibly synthesize micron-scale particles with tunable deformability that can move through the body unrestricted as do red blood cells, opens the door to a new frontier in treating disease,” says Chad Mirkin, professor of chemistry at Northwestern University.
UNC researchers designed the hydrogel material for the study to make particles of varying stiffness. Then, using PRINT technology—a technique invented in DeSimone’s lab to produce nanoparticles with control over size, shape and chemistry—they created molds, which were filled with the hydrogel solution and processed to produce thousands of red blood cell-like discs, each a mere 6 micrometers in diameter.
The team then tested the particles to determine their ability to circulate in the body without being filtered out by various organs. When tested in mice, the more flexible particles lasted 30 times longer than stiffer ones: the least flexible particles disappeared from circulation with a half-life of 2.88 hours, compared to 93.29 hours for the most flexible ones.
Stiffness also influenced where particles eventually ended up: More rigid particles tended to lodge in the lungs, but the more flexible particles did not; instead, they were removed by the spleen, the organ that typically removes old real red blood cells.
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