Using cells genetically modified to produce Siglec-8 on their surfaces and cells without the protein, the researchers tested whether the polymer bound when applied to the cells. As expected, the polymer bound only to the cells that produced Siglec-8. Polymer strands without the sugar, or with different attached sugars, could not bind to the cells. Additionally, when the researchers pretreated Siglec-8-producing cells with antibodies that target the protein, the polymer couldn't attach, suggesting that it specifically targets Siglec-8 and not another protein on the cells.

The researchers validated these results further by testing whether cells adhered to polymer strands immobilized in a petri dish. Cells expressing Siglec-8 bound firmly to the polymer, but didn't bind to polymers without the Siglec-8 specific sugar.

Finally, to test the polymer in a more physiologically relevant setting, the researchers added the polymer to vials of whole human blood to see which blood cells it attached to. They found that the polymer only attached to eosinophils. Using only purified eosinophils, the researchers examined whether the polymer could kill the cells, as the targeted antibodies had in previous experiments. While their results showed that the polymer killed about 65 percent of the eosinophils over 72 hours, it was not as effective as the antibody, which killed up to 90 percent of the cells in 24 hours.

"This is proof that delivering the sugar through a polymer can give you the desired result of selectively engaging Siglec-8 and killing eosinophils, but we still have a long way to go," says Bochner. He and his team plan tto optimize these results, reported in the Journal of Pharmacology and Experimental Therapeutics, by experimenting with other formulations to deliver the sugar to cells, including more rigid polymers, those with denser sugars, or nanoparticles coated with the sugar instead of polymers.

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