SANTA BARBARA, Calif.—Scientists at University ofCalifornia, Santa Barbara (UCSB) and the University of Michigan havecollaborated to develop synthetic particles that closely mimic thecharacteristics and key functions of natural red blood cells, includingsoftness, flexibility and the ability to carry oxygen.
According to the researchers, while syntheticcarriers have brought many advances in drug delivery, they don't match thesophistication of natural biological materials such as red blood cells (RBCs).
One advantage is that synthetic particles can beused to carry drugs where they need to go for more precise targeting than pillsor straight injections. They're already on the market to deliver drugs fordiseases such as prostate cancer, but they have limitations. They don't lastlong because the body's immune cells swoop in quickly and swallow them up.
RBCs are the most prolific type of cell in humanblood, and are highly specialized: they have a unique shape, size andcomposition and they are mechanically flexible, properties that optimize themfor "extraordinary biological performance."
The primary role of natural red blood cells is tocarry oxygen, and the researchers reported that the new synthetic red bloodcells (sRBCs) do that very well, retaining 90 per cent of their oxygen-bindingcapacity after a week.
However, the sRBCs also "deliver therapeutic drugseffectively and with controlled release" and "carry well-distributed contrastagents for enhanced resolution in diagnostic imaging," according to a recentpress release from UCSB.
The primary function of natural red blood cells isto carry oxygen, and the sRBCs do that very well, Synthetic red blood cellsmimic the key structural properties of natural red blood cells including size,shape, mechanical flexibility and oxygen carrying capacity, retaining 90percent of their oxygen-binding capacity after a week. The sRBCs also, however,have been shown to deliver therapeutic drugs effectively and with controlledrelease, and to carry well-distributed contrast agents for enhanced resolutionin diagnostic imaging.
"This ability to create flexible biomimeticcarriers for therapeutic and diagnostic agents really opens up a whole newrealm of possibilities in drug delivery and similar applications," says UCSBchemical engineering professor Samir Mitragotri. "We know that we can furtherengineer sRBCs to carry additional therapeutic agents, both encapsulated in thesRBC and on its surface."
Mitragotri, his research group, and theircollaborators from the University of Michigan succeeded in synthesizing theparticles by creating a polymer doughnut-shaped template, coating the templatewith up to nine layers of hemoglobin and other proteins, then removing the coretemplate. The resulting particles have the same size and flexibility, and cancarry as much oxygen, as natural red blood cells. The flexibility, absent in"conventional" polymer-based biomaterials developed as carriers for therapeuticand diagnostic agents, gives the sRBCs the ability to flow through channelssmaller than their resting diameter, stretching in response to flow andregaining their discoidal shape upon exiting the capillary, just as theirnatural counterparts do.
In addition to synthesizing particles that mimicthe shape and properties of healthy RBCs, the technique described in the papercan also be used to develop particles that mimic the shape and properties ofdiseased cells, such as those found in sickle-cell anemia and hereditaryeliptocytosis. The availability of such synthetic diseased cells is expected tolead to greater understanding of how those diseases and others affect RBCs.
It is believed that the technique employed indeveloping synthetic RBCs can be used to mimic the shape and properties ofdiseased cells. This information can possibly lead to greater understanding ofhow diseases such as sickle-cell anemia and hereditary eliptocytosis and othersaffect RBCs.
The discovery is described in the current onlineedition of Proceedings of the National Academy of Science. UCSB graduatestudent Nishti Doshi was the lead author of the paper; former post-doctoralresearcher Alisar Zahr (now at Harvard Medical School's Schepers Eye ResearchInstitute), Mitragotri and their University of Michigan collaborators SrijananiBhaskar and professor Joerg Lahann were co-authors.