Exploring ceramic vaccines, drug carriers.

Exploring ceramic vaccines, drug carriers

Make a bunch of virus-sized ceramic particles. Now coat them with a laboratory-designed, carbohydrate-like goo, and then let proteins derived from health-wrecking microbes or viruses stick to it. What have you got?

"We may have here a way of making vaccines that nobody has been abl to make," says medical pathologist Nir Kossovsky of the University of California, Los Angeles. His tiny particles also might redeem hundreds of mothballed drug candidates -- ones that showed early promise in test tubes but fizzled in animal or human trials.

The key to such applications -- none of them even close to human trials -- rests in the apparent ability of the coated microscopic crystals to preserve the precise, medically important shape of the delicate proteins adhering to them. That's encouraging, Kossovsky says, because in the body, proteins encounter many molecule-manipulating influences. And the most subtle changes in the shape or structure of a protein can spell dramatic shifts -- sometimes with toxic consequences -- in its biological behavior or therapeutic potential.

The UCLA researchers suspect that as drug and vaccine designers increasingly turn to protein-based agents for disarming viruses, diseased cells or health-threatening biochemicals, stabilizing the proteins' shapes will prove paramount.

In the winter JOURNAL OF APPLIED BIOMATERIALS, Kossovsky, Rointan F. Bunshah and seven collaborators describe experiments using ensembles of specially coated tin oxide ceramic crystals, each about 25 nanometers in diameter. The proprietary sticky coating -- dubbed GF292 -- prevents protein-deforming surface interactions between the particles and the attached molecules, Kossovsky explains.

Antibodies -- the biochemical champs at finding and binding to specific molecular shapes -- had no trouble latching onto transferrin molecules bound to the particules, the UCLA team found. This showed that transferrin, a protein carrier for iron in the blood, retained its precise antibody-attracting structure despite its attachment to the nano-particles, Kossovsky says.

The Epstein-Barr virus (EBV) causes mononucleosis and has been implicated in other ailments. With backing from a Toronto-based technology-development firm, which Kossovsky and Bunshah help manage, the UCLA researchers have begun attaching surface proteins from EBV to the nano-particles with the goal of making safer vaccines from "sterile" decoy viruses.

On rare occasions, vaccines made from real but "killed" viruses have initiated the disease they were designed to prevent. The UCLA researchers expect the immune system will respond to nano-particles robed in the surface proteins of a virus by making antibodies against the virus. Because the cores of the new vaccines are purely ceramic, these decoy viruses cannot cause infection.

Kossovsky also envisions coating the crystalline ceramics particles with oxygen-carrying hemoglobin molecules to make artificial blood.

Acknowledging that biological complexity makes most drug ideas bite the dust, Kossovsky nonetheless asserts, "We have something that is awfully promising."