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.

Genotoxicity of metal oxide nanomaterials: review of recent data and discussion of possible mechanisms

“…During these interactions, the metal oxide/silica NMs might bind and influence DNA replication or disturb other DNA processes, for example, transcription to RNA. 225 Several studies support the hypothesis of direct primary genotoxicity of NMs indicating binding with DNA, [226][227][228][229][230][231][232][233][234][235][236][237][238][239] although many of them are computational studies. [231][232][233][235][236][237][238] Palchoudhury et al, 227 using gel electrophoresis, studied platinum-attached iron oxide NMs' interaction with DNA and showed that DNA has strong interaction with iron oxide NMs attached to platinum.…”

“…Several studies support the hypothesis of direct primary genotoxicity of NMs indicating binding with DNA [223][224][225][226][227][228][229][230][231][232][233][234][235][236], although many of them are computational studies [228][229][230][232][233][234][235]. Palchoudhury et al [224], using gel electrophoresis, studied platinum-attached iron oxide NMs' interaction with DNA and showed that DNA has strong interaction with iron oxide NMs' attached to platinum.…”

Antibacterial and Antifungal Thioglycolic Acid‐Capped Silver Nanoparticles and Their Application on Wool Fabric as a Durable Antimicrobial Treatment

“…investigated the antimicrobial performance of variously modified chitosan and they found that chitosan conjugated with TGA showed markedly better activity against Streptococcus sobrinus (Gram‐positive bacteria), Neisseria subflava (Gram‐negative bacteria) and Candida albicans (fungi) than the chitosan alone. Tang et al . found that compared to unmodified CdSe quantum dots, TGA‐coated CdSe quantum dots showed genotoxicity as they interacted with DNA through groove‐binding.…”

Cellular Targets and Mechanisms in the Cytotoxic Action of Non-biodegradable Engineered Nanoparticles

“…Quantum dots, containing cadmium and lead, cause genotoxic damage by release of these metals, which subsequently may inhibit DNA repair and induce methylation of nucleotides [85]. In addition to that, direct binding of CdSe quantum dots to adenine and thymidine-rich regions of the DNA was attributed to the genotoxic effect of these NPs [86]. Aberrant clusters of topoisomerase I induced by SiO 2 NPs can cause alterations in DNA transcription [87].…”