The Role of Mitchondria in the Potential Hepatotoxicty Caused by Cadmium Telluride Quantum Dot Nanoparticles

Nanotechnology has widespread applications in a variety of fields, thus raising concerns about the potential health risk of nanomaterials. Nanoparticle (NP) toxicity is often linked to their novel physiochemical properties which allow them to be transported across cell membranes or to be taken up into target cells, causing changes in sub-cellular structures and affecting cellular activity. This thesis focused on quantum dots (QDs) which are engineered NPs of semiconductor structures. Cadmium-based QDs such as cadmium telluride QDs (CdTe-QDs), owing to their unique optical and electronic properties, have gained much interest as emerging fluorophores and are widely used in microelectronic and biomedical applications. However, the toxicity associated with these NPs has been a concern and needs to be thoroughly investigated. The overall objectives of this thesis were 1) to examine hepatotoxicity of CdTe-QDs in a hepatocyte cell line and in a mouse model and 2) to investigate mitochondrial effects as the underlying mechanisms of CdTe-QD hepatotoxicity. In HepG2 cells, CdTe-QDs induced cytotoxicity and oxidative stress by increasing reactive oxygen species production and interfering with antioxidant defenses, ultimately activating extrinsic and intrinsic apoptosis pathways. CdTe-QDs also caused mitochondrial toxicity, including mitochondrial enlargement, membrane potential disruption, electron transport chain (ETC) complexes alterations, decreased cellular respiration, ATP depletion, and mitochondrial biogenesis activation. Exposure of BALB/c mice to CdTe-QDs via intravenous injection revealed that the liver was the main target tissue for toxicity. Hepatotoxicity was evidenced by changes in the liver tissue architecture and liver injury biomarkers. At the cellular level, CdTe-QDs induced liver oxidative stress and apoptosis. Effects on mitochondria of liver hepatocytes were also observed, including enlargement and increased number of these organelles and effects on ETC complexes and ATP synthesis. This thesis demonstrates that mitochondria are the prominent targets for CdTe-QD hepatotoxicity as mitochondrial dysfunction resulted in energy metabolism impairment and intracellular oxidant stress that signaled apoptotic pathways, leading to observed cytotoxicity and liver damage in the test models. This thesis provides insights into the toxicological mechanisms of QDs in biological systems and helpful information towards bridging the gap between in vitro and in vivo testing for risk assessment of these NPs.