What we learned from toxicological studies for cadmium-based quantum dots in mice

抄録

Quantum dot 705 (QD705) is a cadmium/selenium/tellurium (Cd/Se/Te)-based nanocrystal. The near-infrared fluorescence emitted by QD705 may render it useful as a probe for detecting vasculature and imaging in vivo. To evaluate the safety of QD705 for clinical application, we conducted a series of toxicology studies in mice. First, we investigated kinetics and tissues distribution of QD705 after intravenous injection. Compared with Cd ion, QD705 had a longer retention time in plasma, spleen, carcass and kidneys, and accumulated in spleen, liver, and kidneys up to 6 months. Tissues distribution of QD705 could be predicted by a physiologically-based pharmacokinetic model. Furthermore, QD705 slowly degraded and released toxic Cd ion in the kidneys. Toxicities were observed in the liver and kidneys on week 12 and 16. Because drug delivery via the lung and lung imaging are potential applications of QDs, we also evaluated the biological effects of QD705 in the lungs of mice. Intratracheal instillation of a single dose of QD705 reduced pulmonary function and persistently induced acute neutrophil infiltration, followed by interstitial lymphocyte infiltration and a granulomatous reaction on day 17 and 90. We further observed that Toll-like receptor pathways were important mechanisms for QD705-induced inflammatory reactions in mouse macrophages. In summary, QD705 tended to accumulate in certain tissues with delayed degradation and toxicities in target organs for weeks later after intravenous injection. The lung was a dangerous route of administration for QD705. While some QD705 remained intact after intratracheal instillation, QD705 induced acute and persistent adverse responses in the lung.