Cytotoxicity Evaluation of Ammonia-Modified Graphene Oxide Particles in Lung Cancer Cells and Embryonic Stem Cells

Abstract

Potential toxicity of graphene oxide (GO) is a subject of increasing research interest in the recent years. Here, we have evaluated the cytotoxicity of ammonia-modified GO (GO-NH2) and pristine GO particles in human lung cancer cells, A549 and embryonic stem cells, Lep3 exposed to different particles concentrations (0.1, 1, 10, 20, and 50 μg/ml) for different times (24 and 48h). Compared with GO, GO-NH2 particles possessed smaller size, positive surface charge and higher thickness. An increased propensity to aggregation in cell cultures was also found for GO-NH2 particles. Cytotoxicity evaluation revealed that GO-NH2 particles are more toxic than pristine GO. Applied at concentrations of 10, 20 and 50 μg/ml for 24h they affect significantly cell morphology of viable embryonic stem cells whereas human lung cancer A549 cells seem to be relatively more resistant to short-time exposure. After 48h exposure however cell proliferation of A549 cells was strongly suppressed in a dose-dependent manner while the proliferation ability of embryonic stem cells was not affected. These results suggested that both GO particles exert different degree of cytotoxicity which is time, dose and cell dependent. In general, ammonia-modified GO particles are more toxic than the pristine GO which should be taken into account for future biomedical applications.

Amination of Graphene Oxide Leads to Increased Cytotoxicity in Hepatocellular Carcinoma Cells

“…Compared with pristine GO, haGO-NH 2 sheets were more wrinkled (the right micrograph at Figure 2A) with no other morphological changes being detected. Similar morphologies for both, pristine and aminated by ammonia GO sheets have been observed in our previous studies [21], indicating that the different methods of amination of GO resulted in a similar effect on GO morphology, namely increasing the level of crumpling of the modified GO sheets. Dynamic light scattering (DLS) is a particularly important technique for determining nanoparticle size and size distribution in aqueous suspensions.…”

“…PEGylation reduces the non-specific binding of GO to biological membranes and improves its in vivo pharmacokinetics for better tumor targeting [18,19]. In our previous study, we found that exposure to ammonia-modified GO NPs could induce cell cycle arrest in the G2/M phase, thus, significantly increasing the apoptosis rate and the generation of reactive oxygen species (ROS) in colorectal Colon 26 and lung A549 cancer cells, but did not influence the viability of non-tumor embryonic stem cells [20,21]. Our findings highlight the potential of GOs NPs to be used as anticancer drugs.…”

Graphenic Materials for Biomedical Applications

“…The non-tumor embryonic stem cell morphology was strongly influenced, whereas cancerous A549 cells better withstood short-term exposure. After 48 h of exposure, the embryonic stem cells proliferative ability remained unaffected and, on the contrary, a strong effect on A549 cell proliferation was demonstrated [63].…”

“…Previous studies have shown that the information obtained on the in vitro and in vivo toxicity of GBMs due to their dimensions and variation in oxidation states is far from complete [60]. The interactions of living cells with GBMs depends on their hydrophilicity, surface chemistry, purity, lateral dimensions, layer number, and dose [61][62][63][64]. These properties vary greatly according to their synthesis eventually to methods of functionalization.…”

“…The cytotoxicity of pristine GO and GO, modified with ammonia (GO-NH 2 ), in cancerous cells A549 of human lung tissue and human non-tumor embryonic stem Lep3 cells after exposition to five particle concentration levels (0.1, 1, 10, 20, and 50 µg/mL) for 24 and 48 h was evaluated [63]. Characterization of the prepared GO-NH 2 particles showed they possess a higher thickness but smaller size, with a positive charge of surface and an increased ability to aggregate in cell cultures compared to GO.…”