Functionalized Graphene Oxide Thin Films for Anti-tumor Drug Delivery to Melanoma Cells

Abstract

Since Graphene discovery, their associated derivate nanomaterials, Graphene Oxide (GO) and reduced-GO were in the forefront of continuous developments in bio-nano-technology due to unique physical-chemical properties. Although GO nano-colloids (GON) were proposed as drug release matrix for targeting cancer cells, there is still a concern regarding its cytotoxicity issues. In this study, we report on the fabrication of functional GON bio-coatings by Matrix-Assisted Pulsed Laser Evaporation (MAPLE) to be used as drug carriers for targeting melanoma cells. We first performed a thorough in vitro cytotoxicity assay for comparison between GON and protein functionalized GON coatings. As functionalization protein, Bovine Serum Albumin (BSA) was non-covalently conjugated to GO surface. Safe concentration windows were identified in cytotoxicity tests by live/dead staining and MTS assays for five different human melanoma cell lines as well as for non-transformed melanocytes and human dermal fibroblasts. Hybrid GON-BSA nano-scaled thin coatings incorporating Dabrafenib (DAB) and Trichostatin A (TSA) inhibitors for cells bearing BRAF V600E pathway activating mutation were assembled on solid substrates by MAPLE technique. We further demonstrated the successful immobilization for each drug-containing GON-BSA assembling systems by evaluating cellular BRAF activity inhibition and histone deacetylases activity blocking, respectively. DAB activity was proven by the decreased ERK phosphorylation in primary melanoma cells (SKmel28 BRAF V600E cell line), while TSA effect was evidenced by acetylated histones accumulation in cell's nuclei (SKmel23 BRAF WT cell line). In addition, melanoma cells exposed to GON-BSA coatings with compositional gradient of inhibitors evidenced a dose-dependent effect on target activity. Such functional bio-platforms could present high potential for cell-biomaterial interface engineering to be applied in personalized cancer therapy studies.

Histone Deacetylase Inhibitor Trichostatin A Reduces Endothelial Cell Proliferation by Suppressing STAT5A-Related Gene Transcription

“…Clinical studies have demonstrated that HDACi can affect different biological processes ( 21 ). In the present study, we explored the direct effects of TSA on endothelial cell gene expression, proliferation, and tube formation.…”

Biomimetic Coatings Obtained by Combinatorial Laser Technologies

“…Inorganic, organic, hybrid coatings: Chitosan/ bio-mimetic apatite [61], CaPs, biopolymers [62,63] Levan and Chitosan blends [64], Graphene Oxide, BSA protein, drugs [65]/Implant devices, drug delivery, model surfaces.…”

“…Since then, MAPLE has evolved to produce a broad spectrum of organic, inorganic, and hybrid coatings [109][110][111][112] for various biomedical applications as well as for energy [113][114][115], sensing [116][117][118], wearable electronics, and photonic devices [98,119]. Indeed, although initially designed for polymers, the method proved successful for a large variety of compounds such as proteins [106,107], enzymes [120,121], polysaccharides [103,122,123], calcium phosphates [24,55,124,125], nanoparticles [126,127], proteins and drug functionalized graphene oxide [65], or carbon nanostructures embedded in organic matrices [128]. Its maturity has already been achieved and existing commercial installations fulfil the anticipations of the scientific community [129].…”

“…The goal of adopting such irradiation geometry is necessary when the generation of compositional gradient coatings is applied in a single-step process. One possible application revealed a possibility of investigating a drug dose-dependent effect when incorporated into the coatings, with respect to controlled delivery for cancer studies [65].…”

Gold Nanoparticles and Graphene Oxide Flakes Synergistic Partaking in Cytosolic Bactericidal Augmentation: Role of ROS and NOX2 Activity

“…The graphene family materials, including graphene oxide (GO), reduced/functionalized graphene oxide (rGO), graphene quantum dots, graphene nanoribbons, 3D (three-dimensional) graphene foam, and graphene nanopores, all are known to exert enormous effects in various biomedical applications. These materials were tried as antibacterial [25,26], anticancer [27,28], drug delivery [29][30][31], bio-sensing [32][33][34], and bio-imaging [35,36] processes owing to their differential interactions with biosystems and biomolecules under in vivo and in vitro conditions. This potential ascended from the characteristic physical, chemical, and mechanical properties of NPs and flakes to participate in biological processes at subcellular, cellular, and upcellular levels and scales.…”