The Low Toxicity of Graphene Quantum Dots is Reflected by Marginal Gene Expression Changes of Primary Human Hematopoietic Stem Cells

Abstract

Graphene quantum dots (GQDs) are a promising next generation nanomaterial with manifold biomedical applications. For real world applications, comprehensive studies on their influence on the functionality of primary human cells are mandatory. Here, we report the effects of GQDs on the transcriptome of CD34 + hematopoietic stem cells after an incubation time of 36 hours. Of the 20 800 recorded gene expressions, only one, namely the selenoprotein W, 1, is changed by the GQDs in direct comparison to CD34 + hematopoietic stem cells cultivated without GQDs. Only a meta analysis reveals that the expression of 1171 genes is weakly affected, taking into account the more prominent changes just by the cell culture. Eight corresponding, weakly affected signaling pathways are identified, which include, but are not limited to, the triggering of apoptosis. These results suggest that GQDs with sizes in the range of a few nanometers hardly influence the CD34 + cells on the transcriptome level after 36 h of incubation, thereby demonstrating their high usability for in vivo studies, such as fluorescence labeling or delivery protocols, without strong effects on the functional status of the cells.

Synthesis of graphene quantum dots and their applications in drug delivery

“…Similar with graphene, GQDs have capability to bind with a variety of aromatic bimolecular through the π–π stacking interaction and/or electrostatic binding. However compared with graphene sheets, GQDs exhibit improved biocompatibility and minimal toxicity [ 16 – 18 ], making them more promising materials for delivering of biologically active cargoes into living systems. In recent years, many researchers have been dedicated to the application of GQDs in drug delivery systems [ 19 – 21 ].…”

Uptake of carbon nanodots into human AML cells in comparison to primary hematopoietic cells

“…A smaller uptake avidity of CD3 + T and T helper cells compared to CD19 + B cells from healthy donors was already observed in our previous study. 19 The difference between these two types of lymphoid cells may relate to the phagocytic ability of activated B cells. 39 The t-SNE plots (Fig.…”

“…Based on the results of previous studies in HSCs and human breast cancer cells using a counterstaining method these clusters could be localized to lysosomes. 19,40 It is therefore conceivable that the CNDs following ingestion into the leukemic blasts are stored in the lysosomes, suggesting that the endolysosomal pathway is also effective in AML cells. In the light of this nding the results of Folkerts et al are interesting and of potential therapeutic relevance.…”

“…[10][11][12][13] As far as living cells are concerned, CNDs enter the cytoplasm of many human cell lines as well as of primary human blood cells, without signicant effects on the cell viability. [14][15][16][17][18][19] As for other nanoparticles, CNDs have been used in studies for cancer diagnosis or drug delivery. [20][21][22][23][24][25][26] In this context, the question arises whether the uptake of CNDs by malignant primary cells differs from that observed for healthy cells.…”

Graphene Quantum Dots as Flourishing Nanomaterials for Bio-Imaging, Therapy Development, and Micro-Supercapacitors

“…The desirable biocompatibility was related with the small sizes and ease of clearance from their body and high oxygen content [ 106 ]. In a very recent study, it was demonstrated that GQDs can alter one gene’s expression on CD 34+ hematopoietic stem cells after 36 hours of incubation, which is a negligible number within 20,800 genes [ 107 ].…”