“Quantum dots are great biological labels for long-term tracking of live cells in vitro,” the university’s Sangeeta Bhatia told nanotechweb.org. “In this application, the toxicity of zinc sulphide-capped CdSe quantum dots is negligible - we showed that quantum dots remain intracellular and fluorescent even after a week in culture with sensitive primary cells, with no effects on viability or function.”

But Bhatia reckons the outlook is more bleak for in vivo applications. “Long-term ultraviolet (UV) exposure resulted in high levels of cadmium-ion formation and cytotoxicity in hepatocytes [liver cells],” she explained. “Even with an inorganic (ZnS) and organic (BSA) capping layer, cadmium release still occurred.”

Bhatia and colleagues prepared CdSe quantum dots using the solvent tri-n-octylphosphine oxide (TOPO) in an inert atmosphere and employed mercaptoacetic acid (MAA) to make the dots water-soluble. These quantum dots were not cytotoxic. But exposing TOPO-coated quantum dots to air before modifying them with MAA produced quantum dots that did cause cytotoxic effects. Applying UV light to MAA-coated CdSe dots had the same effect. The researchers believe that both these findings were due to the release of free cadmium ions from the quantum-dot cores.

The scientists also looked at the protective effect of adding one or two monolayers of ZnS as a surface coating on the quantum dot. The coating virtually eliminated cytotoxicity following exposure of the quantum dots to air, but UV light did still induce some cytotoxicity. Adding a protein shell of bovine serum albumin (BSA) around the ZnS-capped quantum dot reduced this toxicity further but did not remove it completely.

While Bhatia says such a high level of UV exposure would not normally occur in vivo, there are other mechanisms of oxidation (for example phagocytosis by macrophages) that could cause breakdown of the particles. “In any case, to be cleared from the body, these particles must be broken down, as their size dictates clearance intact would be a rare event,” she added.

Now, the researchers plan to look at the non-specific uptake and clearance of a variety of nanoparticles and particle coatings. “If therapeutic particles are to be designed, some thought must be given to their breakdown and exit from the body,” said Bhatia. “Additionally, non-specific uptake of circulating nanoparticles by macrophages of the reticuloendothelial system (RES) [in the liver] is a reality (though strategies exist to evade this system).”

The researchers reported their work in Nano Letters.