Comprehensive Analysis of the Effects of CdSe Quantum Dot Size, Surface Charge, and Functionalization on Primary Human Lung Cells

The growing potential of quantum dots (QDs) in applications as diverse as biomedicine and energy has provoked much dialogue about their conceivable impact on human health and the environment at large. Consequently, there has been an urgent need to understand their interaction with biological systems. Parameters such as size, composition, surface charge, and functionalization can be modified in ways to either enhance biocompatibility or reduce their deleterious effects. In the current study, we simultaneously compared the impact of size, charge, and functionalization alone or in combination on biological responses using primary normal human bronchial epithelial cells. Using a suite of cellular end points and gene expression analysis, we determined the biological impact of each of these properties. Our results suggest that positively charged QDs are significantly more cytotoxic compared to negative QDs. Furthermore, while QDs functionalized with long ligands were found to be more cytotoxic than those functionalized with short ligands, negative QDs functionalized with long ligands also demonstrated size-dependent cytotoxicity. We conclude that QD-elicited cytotoxicity is not a function of a single property but a combination of factors. The mechanism of toxicity was found to be independent of reactive oxygen species formation, as cellular viability could not be rescued in the presence of the antioxidant n-acetyl cysteine. Further exploring these responses at the molecular level, we found that the relatively benign negative QDs increased gene expression of proinflammatory cytokines and those associated with DNA damage, while the highly toxic positive QDs induced changes in genes associated with mitochondria! function. In an attempt to tentatively rank the contribution of each property in the observed QD-induced responses, we concluded that QD charge and ligand length, and to a lesser extent, size, are key factors that should be considered when engineering nanomaterials with minimal bioimpact (charge > functionalization > size).