Red blood cells are not just vehicles that transport oxygen in our bodies: they also clear harmful substances from the bloodstream. Scientists at Johns Hopkins University recently investigated how synthetic biomimicking (or “biomimetic”) nanoparticles, masquerading as red blood cells, can best pull off the same feat in mice. They found that molding these impostors into nonspherical shapes before disguising them improved performance.
Previous work had shown that coating synthetic nanoparticles in membranes borrowed from real red blood cells lets the particles act like cleansing sponges. “By injecting a lot of these particles into the blood, we create decoys that soak up the toxins [so] there's less harm to healthy cells,” says Jordan Green, a biomedical engineer at Johns Hopkins and senior author on a new study of the technique, published in April in Science Advances.
The researchers first manufactured spherical nanoparticles from a biodegradable polymer that is known to be safe and is widely used in therapeutic devices. They then stretched the particles into shapes resembling tiny, flattened Frisbees and elongated footballs. Finally, they wrapped some of each shape in the membranes, which they stripped from mouse red blood cells.
The team had hypothesized that nanoparticles shaped like disks—as real red blood cells are—would better absorb toxins because of their increased surface area. To test which shape worked best, the researchers injected each variety into mice that had been exposed to a typically lethal dose of toxin from Staphylococcus aureus bacteria. Green and his colleagues report that the football-shaped, membrane-coated particles survived the longest before being cleared by the immune system—almost seven times longer than uncoated spheres. Mice treated with spherical particles, even coated ones, did not live much longer than those left untreated. But a third of the mice treated with coated Frisbee-shaped particles, and half of those treated with coated football-shaped ones, were alive and healthy a week later.
Green notes that even though the Frisbee-shaped particles matched red blood cells' shape more closely, the football-shaped ones worked better. “It tells us that there are other things the disk shapes didn't mimic, including the elasticity of [red blood cells] that deform as they flow,” he says. He adds that the football-shaped ones most likely move through the blood more easily.
Other studies “have found that [nonspherical] shapes and biomimetic membrane coatings could, separately, enhance the lifetime of synthetic particles in the bloodstream,” says Dyche Mullins, a cellular and molecular pharmacologist at the University of California, San Francisco, who was not involved in the research. But “this study now demonstrates a synergy between the two effects.”