• 文献标题:   Functionalized Graphene Oxide Thin Films for Anti-tumor Drug Delivery to Melanoma Cells
  • 文献类型:   Article
  • 作  者:   SIMA LE, CHIRITOIU G, NEGUT I, GRUMEZESCU V, OROBETI S, MUNTEANU CVA, SIMA F, AXENTE E
  • 作者关键词:   nanomaterial, graphene oxide, thin film, maple, cytotoxicity, drug delivery, melanoma
  • 出版物名称:   FRONTIERS IN CHEMISTRY
  • ISSN:   2296-2646
  • 通讯作者地址:   Romanian Acad
  • 被引频次:   2
  • DOI:   10.3389/fchem.2020.00184
  • 出版年:   2020

▎ 摘  要

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.