The cadmium–mercaptoacetic acid complex contributes to the genotoxicity of mercaptoacetic acid-coated CdSe-core quantum dots

Abstract

Quantum dots (QDs) have many potential clinical and biological applications because of their advantages over traditional fluorescent dyes. However, the genotoxicity potential of QDs still remains unclear. In this paper, a plasmid-based system was designed to explore the genotoxic mechanism of QDs by detecting changes in DNA configuration and biological activities. The direct chemicobiological interactions between DNA and mercaptoacetic acid-coated CdSecore QDs (MAA–QDs) were investigated. After incubation with different concentrations of MAA–QDs (0.043, 0.13, 0.4, 1.2, and 3.6 μmol/L) in the dark, the DNA conversion of the covalently closed circular (CCC) DNA to the open circular (OC) DNA was significantly enhanced (from 13.9% ± 2.2% to 59.9% ± 12.8%) while the residual transformation activity of plasmid DNA was greatly decreased (from 80.7% ± 12.8% to 13.6% ± 0.8%), which indicated that the damages to the DNA structure and biological activities induced by MAA–QDs were concentration-dependent. The electrospray ionization mass spectrometry data suggested that the observed genotoxicity might be correlated with the cadmium–mercaptoacetic acid complex (Cd–MAA) that is formed in the solution of MAA–QDs. Circular dichroism spectroscopy and transformation assay results indicated that the Cd–MAA complex might interact with DNA through the groove-binding mode and prefer binding to DNA fragments with high adenine and thymine content. Furthermore, the plasmid transformation assay could be used as an effective method to evaluate the genotoxicities of nanoparticles.

Keywords:

• genotoxicity
• MAA CdSe quantum dots
• cadmium-MAA complex
• transformation assay
• DNA

Acknowledgments

This work was supported by the National Natural Science Foundation of China (20677044, 30971573), the Science Fund for Creative Research Groups of NSFC (20621502, 20921062), National High-tech R&D Program of China (863 Program) (2007 AA06Z407), the Fundamental Research Funds for the Central Universities (3081001), and the National Fund for Fostering Talents of Basic Science (J1103513). We would also like to thank Dr. Yong Li (Wuhan University), Dr. Yan Zhang (Wuhan University) and Dr. Jingwei Gao (Wuhan University) for technical assistance and helpful discussion.

Disclosure

The authors report no conflicts of interest in this work.