Tiny particles that have the bendable flexibility of red blood cells can skirt pass the body’s defenses and circulate in the body longer than harder, rigid ones, a new study shows.
These particles can be especially useful in delivering drugs or killing cancer cells – or even creating synthetic blood.
To deliver oxygen throughout the body, red blood cells (RBCs) have to be super flexible. They can deform many thousands of times during their lifetimes as they pass through pores in organs and blood vessels that have smaller diameters than themselves. But as they age towards 120 days, they become less flexible and ultimately get filtered out of the body. (Also, cancer cells are thought to spread into new locations because they are softer and more elastic than healthy cells.)
“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 coauthor Joseph DeSimone. “We believe this study represents a real game changer for the future of nanomedicine.”
He and other researchers from the University of North Carolina, Chapel Hill created particles made of ‘hydrogel polymer’ that have the same size and shape of mouse red blood cells (pictured). They are 6 micrometers in diameter.
They engineered an entire series of these RBC-mimicking particles with varying degrees of ‘deformability.’ Then they injected the squishy particles into both artificial devices and live mice.
"We're the first to test this in a living system," says first author Timothy Merkel.
The most twisty, stretchy ones stayed in circulation longest. In fact, 30 times longer than stiffer particles, which got trapped in the narrow capillaries of the lungs and other organs.
Most of the most springy particles ended up in the spleen (just like real RBCs), bypassing the liver. That finding could have useful implications, DeSimone says. "There are lot of drugs you don't see on the market, as they get screened out because they have liver toxicity." As Merkel says, "Avoiding liver uptake could open up a large therapeutic window."
Watch a video of the synthetic RBCs squeezing through a tiny channel.
As Nature reports:
DeSimone suggests that if future studies bear out his team's findings, the results could be applied in several areas, such as the manufacture of synthetic blood, development of longer-acting and better-targeted delivery of imaging agents and pharmaceuticals (including cancer drugs), and even a potential use in the removal of harmful substances. "Imagine if you were removing cholesterol," DeSimone suggests: the drug could be designed so that it acts like "an empty truck that, as it drives around getting filled up, gets triggered to be removed".
Although these preliminary findings are a promising advance, synthetic blood isn't likely to be just around the corner. Yet, DeSimone says hopefully, applications for the delivery of cancer drugs could be in early clinical trial stages within four years.
The research was published in the Proceedings of the National Academy of Sciences yesterday. It was funded by the National Heart, Lung and Blood Institute, the National Science Foundation, the Carolina Center for Cancer Nanotechnology Excellence, the NIH Pioneer Award Program and Liquidia Technologies, a privately held nanotechnology company.
Image: flexible hydrogel particles / Timothy J. Merkel and Joseph M. DeSimone, UNC