The effect of intracellular degradation on cytotoxicity and cell labeling efficacy of inorganic ligand-stabilized colloidal CdSe/CdS quantum dots

Abstract

Quantum dots (QDots) are explored in biomedicine as highly fluorescent, photostable nanomaterials, but their use is impeded by their hydrophobic nature. In the present work, we evaluate the potential biomedical use of QDots that have been transferred into the aqueous phase by means of inorganic ligands. CdSe/CdS QDots were prepared and transferred to water upon ligand exchange to S2- ions. However, a multiparametric evaluation of the effect of these QDots on multiple cell types revealed significant QDot cytotoxicity. Using optimized methods, the QDots were found to rapidly degrade under endosomal pH, resulting in leached Cd2+. Together with the induction of oxidative stress, this significantly affected cell viability. Using proliferation-restricted cells, QDot degradation was found to augment cytotoxicity with time resulting in mitochondrial and DNA damage, effects on cell morphology and cell functionality. The final non-cytotoxic concentration was defined at 2 nM, enabling cells to be tracked up to 2 cell divisions. A direct comparison with other QDots and fluorescent particles studied resulted in similar concentrations; however, the functionality of previously analyzed particles was much higher. These data reveal that comparing NP toxicity based on particle concentrations is extremely difficult. A comparison of NPs is better obtained by evaluating NP functionality using a straightforward approach, such as follow-up of QDot fluorescence in dividing cells. These data highlight the importance of (1) considering QDot stability in the intracellular microenvironment, (2) the protective nature of the QDot-stabilizing coating, (3) the need for comparison of particle functionality to understand any observed effects