Long-Term Exposure to CdTe Quantum Dots Causes Functional Impairments in Live Cells

Abstract

Several studies suggested that the cytotoxic effects of quantum dots (QDs) may be mediated by cadmium ions (Cd2+) released from the QDs cores. The objective of this work was to assess the intracellular Cd2+ concentration in human breast cancer MCF-7 cells treated with cadmium telluride (CdTe) and core/shell cadmium selenide/zinc sulfide (CdSe/ZnS) nanoparticles capped with mercaptopropionic acid (MPA), cysteamine (Cys), or N-acetylcysteine (NAC) conjugated to cysteamine. The Cd2+ concentration determined by a Cd2+-specific cellular assay was below the assay detection limit (<5 nM) in cells treated with CdSe/ZnS QDs, while in cells incubated with CdTe QDs, it ranged from approximately 30 to 150 nM, depending on the capping molecule. A cell viability assay revealed that CdSe/ZnS QDs were nontoxic, whereas the CdTe QDs were cytotoxic. However, for the various CdTe QD samples, there was no dose-dependent correlation between cell viability and intracellular [Cd2+], implying that their cytotoxicity cannot be attributed solely to the toxic effect of free Cd2+. Confocal laser scanning microscopy of CdTe QDs-treated cells imaged with organelle-specific dyes revealed significant lysosomal damage attributable to the presence of Cd2+ and of reactive oxygen species (ROS), which can be formed via Cd2+-specific cellular pathways and/or via CdTe-triggered photoxidative processes involving singlet oxygen or electron transfer from excited QDs to oxygen. In summary, CdTe QDs induce cell death via mechanisms involving both Cd2+ and ROS accompanied by lysosomal enlargement and intracellular redistribution.

Quantum dots induce heat shock-related cytotoxicity at intracellular environment

“…On the other hand, both cell types demonstrated substantial resistance against CdSe/ZnS (10 μg/ mL, 24 h), implying that these QDs were not contaminated with cadmium ion prior to use and, more importantly, that they did not release cadmium ions in the cellular environment, at least within the time frame of this measurement. Furthermore, QDs were most often found at lysosome, in agreement with previous findings by Cho et al 2007. Hence, the QD-induced cytotoxicity is expected to be initiated within these organelles.…”

“…Hence, the QD-induced cytotoxicity is expected to be initiated within these organelles. Moreover, Cho et al determined intracellular cadmium ion at the QDs exposure condition (Cho et al 2007). For CdTe QDs (10 μg/mL, 24 h) exposure, the intracellular cadmium concentration is similar level to cadmium chloride (1 μM, 24 h) exposure.…”

“…This result suggests the dependence of the CdTe Qds-induced cytotoxicity on the intracellular free cadmium ions possibly released from lysosome. However, CdSe/ZnS do not release the cadmium ion in intracellular environment, as described by Cho et al 2007. It is known that the expression of HSP70B′ is induced by cadmium ions, but it is also regulated by other cytotoxic stimulations (Schlesinger 1990;Kiang and Tsokos 1998), such as protein denaturation (Welch 1992) or ROS (Ma et al 1998;Gorman et al 1999).…”

“…However, the most useful QDs contain toxic elements, mostly cadmium. Although QDs injection in animals does not trigger nefarious events over a limited timeline (up to a few mo) (Rak-Raszewska et al 2012), concerns have risen about the long-term cytotoxicity of QDs as a consequence of slow degradation of the shell built around the CdSe core upon exposure to the biological milieu (Derfus et al 2004;Michalet et al 2005;Cho et al 2007;Winnik and Maysinger 2013).…”

“…(Lovric et al 2005a(Lovric et al , 2005b. Thus, Cho et al found that QDs' cytotoxicity may not be attributed solely to the toxic effect of released cadmium ion, and concluded oxidative stress is generated both by free cadmium and by photooxidation processes to QDs in a polar aerobic environment (Cho et al 2007). Moreover, Hoshino et al gave strong evidence that QD toxicity is related to the chemical structure of the ligand bound to the QDs surface molecules (Hoshino et al 2004).…”