ABSTRACT
AIM: To investigate the metalloestrogenic effects of cadmium telluride quantum dots (QDs) in both human breast cancer cells and in vivo in mice. MATERIALS & METHODS: Human breast cancer cells (MCF-7 cells) were utilized to study QDs, cadmium and 17ß-estradiol induced estrogen-related genomic and nongenomic signaling. Female prepubescent and ovariectomized adult mice were treated with CdTe QDs to assess whether QD-induced estrogenicity would lead to uterine changes. RESULTS & DISCUSSION: Our findings demonstrate that in vitro cadmium-containing QDs induce cellular proliferation, estrogen receptor α activation, and biphasic phosphorylation of AKT and ERK1/2, comparable with 17ß-estradiol. Green QDs elicited a more robust estrogenic response than orange QDs. Addition of the selective estrogen receptor antagonist, ICI 182780, completely abolished all QD-induced estrogenic effects, suggesting that QD-induced estrogenic signaling is mediated via the estrogen receptor. In vivo, chronic treatment of mice with QDs led to a two- to three-fold increase in uterine weight, comparable or greater than 17ß-estradiol. CONCLUSION: These findings suggest that certain cadmium-containing nanocrystals are endocrine disruptors, whose effects can exceed those induced by ionic cadmium or 17ß-estradiol.
Subject(s)
Cadmium Compounds/administration & dosage , Quantum Dots , Receptors, Estrogen/antagonists & inhibitors , Receptors, Estrogen/metabolism , Tellurium/administration & dosage , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Estradiol/analogs & derivatives , Estradiol/pharmacology , Female , Fulvestrant , Humans , MAP Kinase Signaling System/drug effects , Mice , Oncogene Protein v-akt/drug effects , Oncogene Protein v-akt/metabolism , Phosphorylation/drug effects , Receptors, Estrogen/drug effects , Uterus/drug effectsABSTRACT
AIM: Toxicity of nanoparticles developed for biomedical applications is extensively debated as no uniform guidelines are available for studying nanomaterial safety, resulting in conflicting data obtained from different cell types. This study demonstrates the varied toxicity of a selected type of nanoparticle, cadmium telluride quantum dots (QDs), in three increasingly complex cell models of the peripheral nervous system. MATERIALS & METHODS: QD-induced cytotoxicity was assessed via cell viability assays and biomarkers of subcellular damage in PC12 cells and mixed primary dispersed dorsal root ganglia (DRG) cultures. Morphological analysis of neurite outgrowth was used to determine the viability of axotomized DRG explant cultures. RESULTS & DISCUSSION: Cadmium telluride QDs and their core metals exert different degrees of toxicity in the three cell models, the primary dispersed DRGs being the most susceptible. alpha-lipoic acid is an effective, multimodal, cytoprotective agent that can act as an antioxidant, metal chelator and QD-surface modifier in these cell systems. CONCLUSION: Complex multicellular model systems, along with homogenous cell models, should be utilized in standard screening and monitoring procedures for evaluating nanomaterial safety.
Subject(s)
Cadmium Compounds/toxicity , Cytoprotection , Ganglia, Spinal/cytology , Quantum Dots , Tellurium/toxicity , Thioctic Acid/pharmacology , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Cadmium Compounds/chemistry , Cell Survival/drug effects , Cells, Cultured , Ganglia, Spinal/drug effects , Glutathione/metabolism , Mice , PC12 Cells , Rats , Tellurium/chemistry , Thioctic Acid/chemistryABSTRACT
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.
