The Preliminary Study on the Proapoptotic Effect of Reduced Graphene Oxide in Breast Cancer Cell Lines

Abstract

Breast cancer is the most common cancer diagnosed in women, however traditional therapies have several side effects. This has led to an urgent need to explore novel drug approaches to treatment strategies such as graphene-based nanomaterials such as reduced graphene oxide (rGO). It was noticed as a potential drug due to its target selectivity, easy functionalisation, chemisensitisation, and high drug-loading capacity. rGO is widely used in many fields, including biological and biomedical, due to its unique physicochemical properties. However, the possible mechanisms of rGO toxicity remain unclear. In this paper, we present findings on the cytotoxic and antiproliferative effects of rGO and its ability to induce oxidative stress and apoptosis of breast cancer cell lines. We indicate that rGO induced time- and dose-dependent cytotoxicity in MDA-MB-231 and ZR-75-1 cell lines, but not in T-47D, MCF-7, Hs 578T cell lines. In rGO-treated MDA-MB-231 and ZR-75-1 cell lines, we noticed increased induction of apoptosis and necrosis. In addition, rGO has been found to cause oxidative stress, reduce proliferation, and induce structural changes in breast cancer cells. Taken together, these studies provide new insight into the mechanism of oxidative stress and apoptosis in breast cancer cells.

Characteristics of Graphene Oxide for Gene Transfection and Controlled Release in Breast Cancer Cells

“…Numerous studies have analyzed characteristics of GO to determine its potential use for biomedical applications [ 69 , 117 , 118 ]. These studies have shown that the toxicity depends on the complex interactions of several intrinsic characteristics of GO and extrinsic factors.…”

“…The physiochemical properties, such as the shape, size, oxidation, and functionalization [ 69 , 119 , 120 ], are some of the main characteristics of GOs that can influence their interaction with the biological system. In addition, other experimental parameters, such as the dose of administration, time of exposure of GOs to cells, and type of cell line, represent important discriminating factors that can result in variable toxicity responses [ 118 , 119 , 121 ]. Therefore, to evaluate the toxicity of GO carriers, it is necessary to consider all of these parameters and to find the right ranges and combinations that allow the minimum cytotoxic response to be obtained on normal cells and the maximum one to be obtained on cancerous cells for breast cancer detection and elimination.…”

“…The structure, morphology, and size of GOs are the major parameters that can influence their interaction with cells. Through in vitro experiments, it is also possible to expose specific concentrations of GOs to different cell lines for defined periods of time and to test the influence of the time and concentration on the cytotoxicity in different cell types [ 118 , 122 ]. Following the exposure of cells to GOs, internalization studies highlight the mechanisms of cellular uptake and intracellular distribution that are influenced by the surface charge of the nanocarriers and their exposed functional groups [ 114 , 117 ].…”

“…Regarding the time-dependency of the cytotoxicity, the literature has reported conflicting results. Some studies did not find any relationship between the exposure time to GO and the decrease in viability [ 90 , 114 ], while others observed time-dependent cell death [ 118 , 119 , 122 ]. Chowdhury et al [ 122 ] stated that GO nanoribbons decorated with amphiphilic lipid 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG (DSPE-PEG) could cause a time- and dose-dependent cytotoxicity, even though the cell viability measured in MCF-7 cells for the highest concentration tested (i.e., 400 μg/mL) showed only decreases of 15% and 20% after 24 and 48 h treatments, respectively.…”

“…Some studies have investigated the possibility of using rGO, which is characterized by a higher hydrophobicity that leads to a higher affinity for the cell membrane [ 127 ]. In the work by Krętowski et al [ 118 ], the cytotoxicity of rGO nanoplatelets was analyzed on different breast cancer cell lines (T-47D, MCF-7, MDA-MB-231, ZR-75, Hs 578T) through LDH and propidium iodide staining (PI) tests. The cells were incubated with different amounts of rGO, ranging between 25 and 300 μg/mL, and with two different exposition times (24 and 48 h).…”