Biological impact of Quantum Dots in rodents

Quantum Dots (QDs) are fluorescent semiconductor nanocrystals that have a narrow and tunable emission wavelengths across the visible and infrared spectrum. This makes them a promising tool for in vivo, in vitro and ex vivo imaging (Smith et al., 2000). However, the assessment of biocompatibility and biosafety of QDs is a critical issue for further applications as diagnostic and imaging tools on humans. The work of this thesis focuses on non modified QTracker® 800 QDs, which are a commercial type of QDs with a heavy metals core of CdSeTe, specifically designed for in vivo vascular and tumour imaging, for their emission wavelength in the near infrared spectrum (800nm). The biodistribution of QTracker QDs is assessed in Balb-c mice (40pM, 10μl/g) during 3 weeks following an i.v. injection. Accumulation is monitored using inductively coupled plasma mass spectroscopy, optical imaging, confocal microscopy and electron microscopy, and revealed a major accumulation of QDs in liver and spleen, specifically in the mononuclear phagocytic system. The accumulation in the brain is observed over 3 weeks, suggesting a long biological half-life, in the scale of weeks or months. It is in particularly observed around blood vessels, in different brain areas. QDs are found in neurons, glia and epithelial cells, both in cytosol and nucleus. Animal’s behaviour is investigated and novel object recognition test shows that QDs can significantly impair recognition memory at 3 weeks after treatment (with no locomotory and coordination alterations observed). Such impairment is possibly due to the alteration of physiological conditions in the anatomical regions that encode for recognition memory, such as enthorinal and perirhinal cortices, dentate gyrus and areas CA1-CA3 of hippocampus. Therefore, an increased inflammatory response in terms of microglia and astrocytes activation is observed in all these regions. However, it do not have an effect on hippocampal plasticity, which is investigated by measuring long term potentiation (LTP) at 1 and 3 weeks after treatment. Taken together, the data presented in this thesis suggest that due to long term accumulation, induction of neuroinflammation and behavioural changes, the application of QDs in human should be cautious.