Silica layer-dependent leakage of cadmium from CdSe/ZnS quantum dots and comparison of cytotoxicity with polymer-coated analogues

The cytotoxicity of cadmium-containing quantum dots (QDs) is reportedly caused by released Cd2+ as well as other factors such as ligand, size, and surface modification. The tolerated concentration of QDs therefore deviates from ~ 1 to 1000 nM. However, the concentration of Cd2+ released from QDs has seldom been correctly and systematically measured. We prepared highly emitting silica capsules with incorporated multiple CdSe/ZnS QDs through a sol-gel-derived wet method. The concentration of released Cd2+ in buffer solution was measured as a function of the preparation conditions of the capsules. When the shell thickness of the capsule was 15 nm, the release was effectively suppressed compared with a capsule shell thickness of 10 nm. Heat treatment at 40 °C further suppressed the leakage. When the silicon alkoxide hydrolysis time was increased from 3 to 15 h, and the surface was modified with COOH groups, the leakage reached a minimum of ~ 0.01 ppb for a QD concentration of 10 nM after 15 h of dispersion. This was two orders of magnitude less than polymer-coated analogues with the same surface functional groups. These silica capsules did not show any toxicity to culture cells, whereas the polymer-coated ones showed high toxicity with the same QD concentration. Silica capsules are therefore not only the expected ideal, but show significantly superior performance when correctly prepared for biomedical application with CdSe/ZnS QDs, owing to their strong suppression of Cd2+ leakage into solution.