The effect of nanoparticle degradation on poly(methacrylic acid)-coated quantum dot toxicity: The importance of particle functionality assessment in toxicology

Abstract

Colloidal semiconductor nanoparticles (quantum dots) have attracted a lot of interest in technological and biomedical research, given their potent fluorescent properties. However, the use of heavy metal-containing nanoparticles remains an issue of debate. The possible toxic effects of quantum dots remain a hot research topic and several questions such as possible intracellular degradation of quantum dots and the effect thereof on both cell viability and particle functionality remain unresolved. In the present work, poly(methacrylic acid)-coated CdSe/ZnS quantum dots were synthesized and characterized, after which their effects on cultured cells were evaluated using a multiparametric setup. The data reveal that the quantum dots are taken up through endocytosis and when exposed to the low pH of the endosomal structures, they partially degrade and release cadmium ions, which lowers their fluorescence intensity and augments particle toxicity. Using the multiparametric method, the quantum dots were evaluated at nontoxic doses in terms of their ability to visualize labeled cells for longer time periods. The data revealed that comparing different particles in terms of their applied dose is challenging, likely due to difficulties in obtaining accurate nanoparticles concentrations, but evaluating particle toxicity in terms of their biological functionality enables an easy and straightforward comparison.

Cytosolic Delivery of Nanolabels Prevents Their Asymmetric Inheritance and Enables Extended Quantitative in Vivo Cell Imaging

“…1a. Cells are first incubated with plasmonic NPs, such as gold NPs (AuNPs), for [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] min. During that time the AuNP can adsorb to the cells and are internalized just below the plasma membrane by endocytic uptake (see TEM images in Figure S1).…”

“…Instead, cells labelled by endocytosis exhibited a much more rapid decrease of the cell signal (Fig. 2a, b), due to other processes than cell division alone, most importantly label degradation (CdSe QD) or fluorescence quenching (FD) in the acidic endolysosomes 26,28 .…”

“…In other cases, problems may arise for cells that have a limited life span in culture, such as pancreatic islets, as efficient cell labelling through endocytic uptake is a rather slow process 24 . A second problem is that entrapment of contrast agents in the acidic endolysosomes may lead to increased cytotoxicity, for instance by creating reactive groups on the NP surface or by leaching of toxic metal ions, such as Cd 2+ in case of QDs [25][26][27] . A third disadvantage of endocytic cell labelling is that the vast majority of the contrast agents are trafficked to the endolysosomes where they are exposed to an acidic and overall degrading environment 26,28 .…”

“…A second problem is that entrapment of contrast agents in the acidic endolysosomes may lead to increased cytotoxicity, for instance by creating reactive groups on the NP surface or by leaching of toxic metal ions, such as Cd 2+ in case of QDs [25][26][27] . A third disadvantage of endocytic cell labelling is that the vast majority of the contrast agents are trafficked to the endolysosomes where they are exposed to an acidic and overall degrading environment 26,28 . This can lead to degradation of the contrast agent, lowering the signal intensity, as reported for fluorescent labels [28][29][30] as well as MRI contrast agents [31][32][33] .…”

The performance of gradient alloy quantum dots in cell labeling

“…Although a recent pilot study indicated that these NPs do not cause any acute toxicity in non-human primates [17], long-term effects were not looked into and need to be considered carefully [18]. In vitro data often show high toxicity levels, which are to a large extent caused by the exposure of the QDots to their immediate biological (and degradative) environment, being cellular endo-or lyso-somes and their behavior in this complex biological environment, which results in leaching of free Cd2+ ions and thereby inducing toxicity [19][20][21][22][23].…”