This study successfully synthesized maltodextrin coated cadmium sulfide semiconductor nanoparticles. The results show that CdS-MD nanoparticles can cause cytotoxicity, alter cell, proliferation and induce ROS production in human cell lines; however, the toxicity differed significantly depending on the cell type and CdS-MD nanoparticles concentration. We also showed evidence of the embryotoxic potential of CdS-MD nanoparticles when used in high concentrations. Although, quantum dots have attracted tremendous interest as luminiscent probes in biological and medical research due to their unique properties, their potential application in these fields has been limited due to their toxic effects [21, 22]. Specifically, QDs contain toxic components such as cadmium . Surface modification of QDs is therefore required to enhance stability.
The present study demonstrates that CdS-MD nanoparticles produced different effects on human cell lines, causing cytotoxic effects in MDA-MB-231 cells but inducing cell proliferation of HepG2 and Caco-2 cells depending on concentration. Indeed, some studies suggest that nanoparticles are not inherently benign and that they affect biological behavior at the cellular, subcellular, and protein levels [24–26]. Early studies by Kirchner et al. attempted to quantitatively determine values for the onset of cytotoxicity in CdSe and CdSe/ZnS quantum dots, either coated with mercaptopropionic acid (MPA), embedded in a silica shell or embedded in an amphiphilic polymer Shell . They found that the majority of the nanoparticles were ingested into the cells and were stored in vesicles around the nucleus, irrespective of the surface coating. The toxic ions are commonly thought to be released from quantum dots when the surface of the nanoparticle is oxidized; early reports on the inclusion of simple quantum dots in bacteria support this . Here we synthesized CdS nanoparticles coated with maltodextrin polymer and found cytotoxic effects at high concentrations. It is clear from this and other studies the surface coating is related to the toxicity experienced by the cells, which affects the level of toxic material released from the nanoparticles. The present study supports others indicating that different cell types have varying thresholds for quantum dots-induced toxicity.
Nanoparticles exposures can lead to disturbances in cellular homeostatic mechanisms, resulting either in adaptive cellular responses or cell death . Cell death could occur either through an abrupt process named necrosis or by a tightly regulated or programmed process (apoptosis and autophagy) [13, 30]. There has been a particular focus on DNA when looking at the effects of quantum dots in vitro given that DNA is known to be damaged by cadmium . The morphological characterization of cell death in MDA-MB-231 cells was confirmed by immunofluorescence stain and by transmission electron microscopy (TEM) analysis of ultrastructure. TEM analysis confirmed the presence of the typical morphological features of apoptosis and necrosis in MDA-MB-231 cells after exposure to CdS-MD nanoparticles. Cells undergoing apoptosis show characteristic morphological features such as chromatin aggregation, nuclear and cytoplasmic condensation, partition of cytoplasm and nucleus into membrane bound-vesicles (apoptotic bodies); while the necrotic cells showed a loss membrane integrity, there was no vesicle formation and complete lysis. No cell deaths were observed when cells were treated with 1.64 nM of CdS-MD nanoparticles. However, apoptosis and necrosis were observed at concentrations higher 8.20 nM of CdS-MD nanoparticles, and this phenomenon increased in a dose dependent manner. The present report provides relatively consistent data on the cytotoxicity of QDs.
ROS play a dual role in cell fate, causing cell death as well as acting as second messengers to induce an adaptive cell response . Oxidative stress has in fact been shown to induce cell death through a variety of mechanisms [30, 33]. A hierarchical model for nanoparticles toxicity also describes the possibility of higher oxidative stress levels leading to cell death induction . Different types of QDs have been shown to induce oxidative stress [35, 36], and it was suggested that the photo-activation of QDs resulted in the generation of free radicals such as reactive oxygen intermediates (ROI), which would damage the DNA . This study quantified the amount of ROS production in MDA-MB-231 cells. We found a significant increase in ROS production at concentrations of 11.48 and 14.76 nM of CdS-MD nanoparticles. It has been suggested that toxicity due to the production of reactive oxygen intermediates (ROI) is less controllable because it essentially has no barrier and occurs due to the resonance energy transfer from the quantum dots to molecular oxygen . Lu et al. suggested that CdSe quantum dots were implicated in the apoptosis of human osteoblasts via the generation of ROI, causing the activation of certain enzymes that trigger apoptotic death . Our results agree with this given that we found a significant rate of cell death at high CdS-MD nanoparticles concentrations.
QDs-induced perturbations of cellular mechanisms might act as a basis for different pathophysiological processes depending on concentration and the duration of exposure [21–23]. This study analyzed the effect of prolonged exposure to CdS-MD nanoparticles in MDA-MB-231 cells. We found that cells were alive after 24 hours and that cell proliferation during five days after exposition was not significantly affected; at 7 days, however, we found that cell proliferation had significantly increased with the lower concentration (1.64 nM) and was inhibited using concentrations higher than 4.92 nM at 7 days (p < 0.05). The results presented here indicate that although there initially was an adaptive response, the cytotoxic effect could not be completely eliminated. Proliferation changes in cells incubated with high concentrations suggest the presence of cell death or late cell arrest to repair the damage.
There are no published studies on QDs potential embryotoxicity in mammals. However, several in vitro and in vivo studies suggest local and systemic effects following exposure to nanoparticles . Moreover, some nanoparticles readily travel throughout the body, deposit in target organs and get into many types of cells, lodge in mitochondria, and may trigger injurious responses . Embryotoxicity is an important part of the toxicological profile of any new biologically active substance relevant to human safety. To reduce animal experimentation and predict in vivo embryotoxicity, in vitro tests like the chicken embryo model have been optimized . Di Guglielmo et al.  used a zebrafish embryo model to demonstrate that gold and cobalt ferrite nanoparticles were able to modulate cell differentiation and induce weak embryotoxicity. Fein et al.  used the same model to demonstrate that fluorescent silica nanoparticles and/or aggregates mainly accumulate on the chorion of embryos and exhibit no overt embryotoxicity. By contrast, Bosman et al.  demonstrated that embryo development was not inhibited by exposure to polystyrene-based nanoparticles, suggesting a lack of embryotoxicity.
Our results showed that the tested CdS-MD nanoparticles were embryotoxic at high concentrations: a reduction in the axial skeleton and morphological changes in neural tube, somites, cardiovascular structure and central nervous system were observed. The embryotoxicity induced by cadmium was demonstrated early [46, 47]. Present results indicate that the embryotoxicity mechanisms induced by CdS-MD nanoparticles have direct effects on developing tissue. The nature of the observed abnormalities suggests that these effects could be directly associated with concentration. However, embryotoxicity could also be explained by the chicken embryo model itself and the fact that the CdS-MD nanoparticles were added directly into the eggs.