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UNC Nano Researchers Work on ‘Flexible’ Synthetic Blood Cells

by Editor1 last modified February 22, 2011 - 12:41

A multidisciplinary research team at the University of North Carolina at Chapel Hill has created particles to mirror properties of red blood cells. The work could prove an important step forward in the development of synthetic blood, researchers said.

UNC Nano Researchers Work on  ‘Flexible’ Synthetic Blood Cells

UNC "synthetic' particles are flexible enough to pass through microscopic pores in organs and narrow blood vessels.

UNC researchers used technology known as PRINT (Particle Replication in Non-wetting Templates) to produce very soft hydrogel particles that mimic the size, shape and flexibility of red blood cells. This allowed the particles to circulate in the body for extended periods of time.

While the team did not test capacity for the particles to perform bodily functions (transporting oxygen or drugs) have not been conducted, researchers said the artificial particles, like real blood cells, have one key feature in common – they are both flexible enough to pass through microscopic pores in organs and narrow blood vessels.

To date, artificial red blood cells tend to be quickly filtered out of body circulation due primarily to their inflexibility.

Real red blood cells have a life cycle of approximately 120 days, and gradually become stiffer over their lifespan. Eventually, red blood cells are filtered out of circulation when they can no longer pass through pores in the spleen.

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, the team created “molds” and filled them with the hydrogel solution to produce thousands of red blood cell-like discs, each a mere 6 micrometers in diameter.

The team 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.

How 'Synthetic' Blood Could Improve Cancer Treatments
The findings could also impact cancer treatments because cancer cells are softer than healthy cells, which let cancers lodge in different places in the body. Particles filled with cancer-fighting medicines that can remain in circulation longer may offer alternative treatments, the UNC researchers said.

"Creating particles for extended circulation in the blood stream has been a significant challenge in the development of drug delivery systems from the beginning," said Joseph DeSimone, Ph.D., the study's co-lead investigator. "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."

DeSimone is also Chancellor's Eminent Professor of Chemistry in UNC's College of Arts and Sciences, a member of UNC's Lineberger Comprehensive Cancer Center and William R. Kenan Jr. Distinguished Professor of Chemical Engineering at N.C. State University.

The UNC work has also brought recognition from Dr. Chad Mirkin, Director of Northwestern University’s International Institute for Nanotechnology, and a member of President Obama's Council of Advisors on Science and Technology.

"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," Dr. Mirkin said.

The study was led by Dr. DiSimone and Timothy Merkel, a graduate student in Dr. DeSimone's lab. Other UNC team members include: Kevin P. Herlihy and Farrell R. Kersey from the chemistry department; Mary Napier and J. Christopher Luft from the Carolina Center for Cancer Nanotechnology Excellence; Andrew Z. Wang from the Lineberger Center; Adam R. Shields from the physics department; Huali Wu and William C. Zamboni from the Institute for Pharmacogenomics and Individualized Therapy at the Eshelman School of Pharmacy; and James E. Bear and Stephen W. Jones from the cell and developmental biology department in the School of Medicine.

The research was made possible by a National Institutes of Health stimulus grant, the National Science Foundation, the Carolina Center for Cancer Nanotechnology Excellence, the NIH Pioneer Award Program and Liquidia Technologies, a private nanotechnology firm working with PRINT particle technology.