Metalloestrogenic Effects of Quantum Dots

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 17β-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 17β-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 17β-estradiol. Conclusion: These findings suggest that certain cadmium-containing nanocrystals are endocrine disruptors, whose effects can exceed those induced by ionic cadmium or 17β-estradiol.

Keywords::

• cadmium
• estrogen
• estrogen receptor
• ICI 182780
• MCF-7
• metalloestrogen
• nanoparticles
• quantum dots

Financial & competing interests disclosure

This work was funded by Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council (NSERC), and Fonds de la Recherche en Sante Quebec (FRSQ). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors would like to thank graduate students for their contribution to this study: Alex Moquin for synthesizing multiple batches of various quantum dots, and Kevin Neibert for the Flame atomic absorption and Graphite furnace atomic absorption analysis of cadmium concentration in tissue samples.

Additional information

Funding

This work was funded by Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council (NSERC), and Fonds de la Recherche en Sante Quebec (FRSQ). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.