The performance of gradient alloy quantum dots in cell labeling

Abstract

The interest in using quantum dots (QDots) as highly fluorescent and photostable nanoparticles in biomedicine is vastly increasing. One major hurdle that slows down the (pre)clinical translation of QDots is their potential toxicity. Several strategies have been employed to optimize common coreshell QDots, such as the use of gradient alloy (GA)-QDots. These particles no longer have a sizedependent emission wavelength, but the emission rather depends on the chemical composition of the gradient layer. Therefore, particles of identical sizes but with emission maxima spanning the entire visible spectrum can be generated. In the present study, two types of GA-QDots are studied with respect to their cytotoxicity and cellular uptake. A multiparametric cytotoxicity approach reveals concentration-dependent effects on cell viability, oxidative stress, cell morphology and cell functionality (stem cell differentiation and neurite outgrowth), where the particles are very robust against environmentally-induced breakdown. Non-toxic concentrations are defined and compared to common core-shell QDots analyzed under identical conditions. Additionally, this value is translated into a functional value by analyzing the potential of the particles for cell visualization. Interestingly, these particles result in clear endosomal localization, where different particles result in identical intracellular distributions. This is in contrast with CdTe QDots with the same surface coating, which resulted in clearly distinct intracellular distributions as a result of differences in nanoparticle diameter.The GA-QDots are therefore ideal platforms for cell labeling studies given their high brightness, low cytotoxicity and identical sizes, resulting in highly similar intracellular particle distributions which offer a lot of potential for optimizing drug delivery strategies.

Coating of Quantum Dots strongly defines their effect on lysosomal health and autophagy

“…This could be expected since it has been observed before that NP agglomeration has a negative impact on cellular uptake. [48][49][50] It is therefore likely that we need a higher dosage of MPA-coated QDs to reach similar intracellular fluorescence levels as PEGylated QDs because only the [29] This difference with our data may be attributed to differences in aggregation: their MPA-QDs form smaller aggregates, which could lead to more efficient uptake and consequently toxicity at lower concentrations. This hypothesis was confirmed in vivo in mice where aggregated MPA-QDs exhibited less toxicity than their unaggregated counterparts.…”

“…Furthermore, our group recently reported that cells labeled with GA-QDs can be tracked 1.5 times longer than conventional core-shell QDs. [29] In conclusion, the combination of this excellent functionality and biocompatibility makes these MPA-coated GA-QDs very well suited for cell labeling applications.…”

“…Furthermore, very little attention has yet been paid to the potential harm induced by the highly promising GA-QDs. [29] In addition, many of those studies are limited to one type of coating or lack data on intracellular uptake. [24] In this paper we look into the influence of QD surface chemistry on the toxicity and its underlying causes by comparing two types of QDs that only differ in their coating.…”

“…[30][31][32] As a second coating strategy we selected the short ligand 3-mercaptopropionic acid (MPA) based on previous reports that observed limited toxicity with this coating. [29][30][31] We therefore wanted to analyze this promising observation further with a special focus on autophagy since the influence of MPA coating on this pathway remains unexplored so far. To this end, we examined the aggregation profile, cellular uptake, cytotoxicity and associated ROS levels of QDs, and studied their effect on lysosomes and autophagosomes -the two most essential organelles of the autophagy pathway.…”

Polyethyleneimine-coated quantum dots for miRNA delivery and its enhanced suppression in HepG2 cells

“…CdSe/ZnS QDs were selected as labeling probes for living cells since the gradient alloy CdSe/ZnS QDs possess excellent opticophysical properties and are more compatible with a biological environment by shielding the Cd 2+ -containing core from the ZnS shell structure. 31,32 The recombinant plasmid expression vector of miR-26a, which is capable of inducing green fluorescence and cell cycle arrest in HepG2 cells, 29 was used for the evaluation of gene delivery of PEI/QD NPs in HepG2 cells. CdSe/ZnS QDs were fabricated with PEI coating using a simple method of electrostatic attraction.…”