Non-homogeneous dispersion of graphene in polyacrylonitrile substrates induces a migrastatic response and epithelial-like differentiation in MCF7 breast cancer cells

Abstract

Background Recent advances from studies of graphene and graphene-based derivatives have highlighted the great potential of these nanomaterials as migrastatic agents with the ability to modulate tumor microenvironments. Nevertheless, the administration of graphene nanomaterials in suspensions in vivo is controversial. As an alternative approach, herein, we report the immobilization of high concentrations of graphene nanoplatelets in polyacrylonitrile film substrates (named PAN/G10) and evaluate their potential use as migrastatic agents on cancer cells. Results Breast cancer MCF7 cells cultured on PAN/G10 substrates presented features resembling mesenchymal-to-epithelial transition, e.g., (i) inhibition of migratory activity; (ii) activation of the expression of E-cadherin, cytokeratin 18, ZO-1 and EpCAM, four key molecular markers of epithelial differentiation; (iii) formation of adherens junctions with clustering and adhesion of cancer cells in aggregates or islets, and (iv) reorganization of the actin cytoskeleton resulting in a polygonal cell shape. Remarkably, assessment with Raman spectroscopy revealed that the above-mentioned events were produced when MCF7 cells were preferentially located on top of graphene-rich regions of the PAN/G10 substrates. Conclusions The present data demonstrate the capacity of these composite substrates to induce an epithelial-like differentiation in MCF7 breast cancer cells, resulting in a migrastatic effect without any chemical agent-mediated signaling. Future works will aim to thoroughly evaluate the mechanisms of how PAN/G10 substrates trigger these responses in cancer cells and their potential use as antimetastatics for the treatment of solid cancers. Graphical Abstract

Investigation of Inlet Conditions in The Mixing Process of Nanoparticles and Blood in a T-Shaped Microfluidic Reactor with Small Rectangular Cavities

“…Consequently, many types of microreactors were developed for biomedical applications in order to replace the traditional devices [11]. As a result of the above, a state-of-the-art flat membrane composite material made of polyacrylonitrile and graphene with a certain composition (PAN/G10) was developed in a micromixer device [12]. In this microdevice, the migration of the breast cancer cells due to the specific localization of graphene clusters in the polymer matrix was regulated [12].…”

“…As a result of the above, a state-of-the-art flat membrane composite material made of polyacrylonitrile and graphene with a certain composition (PAN/G10) was developed in a micromixer device [12]. In this microdevice, the migration of the breast cancer cells due to the specific localization of graphene clusters in the polymer matrix was regulated [12]. Cancer cells localized preferentially on top of graphene clusters in PAN/G10 membranes and formed 3D cancer cell islets.…”