Proceedings of the National Academy of Sciences: Red blood cell-mimicking synthetic biomaterial particles
Biomaterials form the basis of current and future biomedical technologies. They are routinely used to design therapeutic carriers, such as nanoparticles, for applications in drug delivery. Current strategies for synthesizing drug delivery carriers are based either on discovery of materials or development of fabrication methods. While synthetic carriers have brought upon numerous advances in drug delivery, they fail to match the sophistication exhibited by innate biological entities. In particular, red blood cells (RBCs), the most ubiquitous cell type in the human blood, constitute highly specialized entities with unique shape, size, mechanical flexibility, and material composition, all of which are optimized for extraordinary biological performance. Inspired by this natural example, we synthesized particles that mimic the key structural and functional features of RBCs. Similar to their natural counterparts, RBC-mimicking particles described here possess the ability to carry oxygen and flow through capillaries smaller than their own diameter. Further, they can also encapsulate drugs and imaging agents. These particles provide a paradigm for the design of drug delivery and imaging carriers, because they combine the functionality of natural RBCs with the broad applicability and versatility of synthetic drug delivery particles
Scientists at UC Santa Barbara, in collaboration with scientists at University of Michigan, have developed synthetic particles that closely mimic the characteristics and key functions of natural red blood cells, including softness, flexibility, and the ability to carry oxygen.
The primary function of natural red blood cells is to carry oxygen, and the synthetic red blood cells (sRBCs) do that very well, retaining 90% 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.
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.
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