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Synthetic red blood cells mimic the real thing
SANTA BARBARA, Calif.— Scientists at University of California, Santa Barbara (UCSB) and the University of Michigan have collaborated to develop synthetic particles that closely mimic the characteristics and key functions of natural red blood cells, including softness, flexibility and the ability to carry oxygen.
According to the researchers, while synthetic carriers have brought many advances in drug delivery, they don't match the sophistication of natural biological materials such as red blood cells (RBCs).
One advantage is that synthetic particles can be used to carry drugs where they need to go for more precise targeting than pills or straight injections. They're already on the market to deliver drugs for diseases such as prostate cancer, but they have limitations. They don't last long because the body's immune cells swoop in quickly and swallow them up.
RBCs are the most prolific type of cell in human blood, and are highly specialized: they have a unique shape, size and composition and they are mechanically flexible, properties that optimize them for "extraordinary biological performance."
The primary role of natural red blood cells is to carry oxygen, and the researchers reported that the new synthetic red blood cells (sRBCs) do that very well, retaining 90 per cent of their oxygen-binding capacity after a week.
However, the sRBCs also "deliver therapeutic drugs effectively and with controlled release" and "carry well-distributed contrast agents for enhanced resolution in diagnostic imaging," according to a recent press release from UCSB.
The primary function of natural red blood cells is to carry oxygen, and the sRBCs do that very well, Synthetic red blood cells mimic the key structural properties of natural red blood cells including size, shape, mechanical flexibility and oxygen carrying capacity, retaining 90 percent of their oxygen-binding capacity after a week. The sRBCs also, however, have been shown to deliver therapeutic drugs effectively and with controlled release, and to carry well-distributed contrast agents for enhanced resolution in diagnostic imaging.
"This ability to create flexible biomimetic carriers for therapeutic and diagnostic agents really opens up a whole new realm of possibilities in drug delivery and similar applications," says UCSB chemical engineering professor Samir Mitragotri. "We know that we can further engineer sRBCs to carry additional therapeutic agents, both encapsulated in the sRBC and on its surface."
Mitragotri, his research group, and their collaborators from the University of Michigan succeeded in synthesizing the particles by creating a polymer doughnut-shaped template, coating the template with up to nine layers of hemoglobin and other proteins, then removing the core template. The resulting particles have the same size and flexibility, and can carry as much oxygen, as natural red blood cells. The flexibility, absent in "conventional" polymer-based biomaterials developed as carriers for therapeutic and diagnostic agents, gives the sRBCs the ability to flow through channels smaller than their resting diameter, stretching in response to flow and regaining their discoidal shape upon exiting the capillary, just as their natural counterparts do.
In addition to synthesizing particles that mimic the shape and properties of healthy RBCs, the technique described in the paper can also be used to develop particles that mimic the shape and properties of diseased cells, such as those found in sickle-cell anemia and hereditary eliptocytosis. The availability of such synthetic diseased cells is expected to lead to greater understanding of how those diseases and others affect RBCs.
It is believed that the technique employed in developing synthetic RBCs can be used to mimic the shape and properties of diseased cells. This information can possibly lead to greater understanding of how diseases such as sickle-cell anemia and hereditary eliptocytosis and others affect RBCs.
The discovery is described in the current online edition of Proceedings of the National Academy of Science. UCSB graduate student Nishti Doshi was the lead author of the paper; former post-doctoral researcher Alisar Zahr (now at Harvard Medical School's Schepers Eye Research Institute), Mitragotri and their University of Michigan collaborators Srijanani Bhaskar and professor Joerg Lahann were co-authors.