3D and 2D cell models in a novel microfluidic tool for evaluation of highly chemically and microbiologically pure graphene oxide (GO) as an effective drug carrier

Abstract

Microfluidic Lab-on-a-Chip systems have gained a lot of interest in cellular research. Currently, two- (2D) and three-dimensional (3D) cancer cell cultures are carried out under microfluidic conditions as new culture models. Mostly, they are used for the evaluation of cancer metastasis and effectiveness of anticancer therapy. Herein, we present a novel microfluidic tool for cancer cell cultures as 2D monolayer and 3D - spheroids simultaneously. The designed device was successfully used to create 4-day cultures of liver (HepG2), breast (MCF-7) and colon (HT-29) cancer cells. Biological properties of chemically and microbiologically pure graphene oxide (GO) were studied on the obtained cancer cell models as a new application of the developed microsystem. We showed that the presented microsystem is an ideal tool for studying the impact of carbon slurries on cell cultures carried out under microfluidic conditions. Moreover, our research showed that GO effect varies depending on its concentration, time after its treatment, origin of cells and the cell model. 2D monolayer cell models was more resistant to GO than 3D spheroids, what can relate with the microsystem geometry. Moreover, we showed that slight cytotoxic effect of GO (cell viability ∼70%) was observed only in 3D liver and breast cancer models. In our best knowledge, this is the first presentation of GO cytotoxicity under environmental conditions which much more reproduce in vivo than standard cell cultures (macroscale). Therefore, the results presented by us can show the real effect of graphene oxide on liver, breast and colon cancer tissue.