Department of Nanobiotechnology, Institute of Biology, Warsaw University of Life Sciences, 02-786 Warsaw, Poland.
Centre for Advanced Materials and Technologies CEZAMAT, Warsaw University of Technology, 02-822 Warsaw, Poland.
Molecules. 2021 Sep 25;26(19):5804. doi: 10.3390/molecules26195804.
Glioblastoma (GBM) is the most common primary and aggressive tumour in brain cancer. Novel therapies, despite achievements in chemotherapy, radiation and surgical techniques, are needed to improve the treatment of GBM tumours and extend patients' survival. Gene delivery therapy mostly uses the viral vector, which causes serious adverse events in gene therapy. Graphene-based complexes can reduce the potential side effect of viral carries, with high efficiency of microRNA (miRNA) or antisense miRNA delivery to GBM cells. The objective of this study was to use graphene-based complexes to induce deregulation of miRNA level in GBM cancer cells and to regulate the selected gene expression involved in apoptosis. The complexes were characterised by Fourier transform infrared spectroscopy (FTIR), scanning transmission electron microscopy and zeta potential. The efficiency of miRNA delivery to the cancer cells was analysed by flow cytometry. The effect of the anticancer activity of graphene-based complexes functionalised by the miRNA sequence was analysed using 2,3--(2-methoxy-4-nitro-5-sulfophenyl)-2-tetrazolium-5-carboxyanilide salt (XTT) assays at the gene expression level. The results partly explain the mechanisms of miRNA deregulation stress, which is affected by graphene-based complexes together with the forced transport of mimic miR-124, miR-137 and antisense miR-21, -221 and -222 as an anticancer supportive therapy.
胶质母细胞瘤(GBM)是最常见的原发性和侵袭性脑癌。尽管在化疗、放疗和手术技术方面取得了进展,但仍需要新的疗法来改善 GBM 肿瘤的治疗方法并延长患者的生存期。基因传递疗法主要使用病毒载体,这会导致基因治疗中的严重不良反应。基于石墨烯的复合物可以降低病毒载体的潜在副作用,从而高效地将 microRNA(miRNA)或反义 miRNA 递送至 GBM 细胞。本研究的目的是使用基于石墨烯的复合物来诱导 GBM 癌细胞中 miRNA 水平的失调,并调节涉及细胞凋亡的选定基因表达。通过傅里叶变换红外光谱(FTIR)、扫描透射电子显微镜和zeta 电位对复合物进行了表征。通过流式细胞术分析了 miRNA 递送至癌细胞的效率。通过使用 2,3--(2-甲氧基-4-硝基-5-磺苯基)-2-四唑-5-羧基苯胺盐(XTT)测定法在基因表达水平上分析了 miRNA 序列功能化的基于石墨烯的复合物的抗癌活性。结果部分解释了 miRNA 失调应激的机制,该应激受基于石墨烯的复合物以及模拟 miR-124、miR-137 和反义 miR-21、-221 和 -222 的强制转运的影响,作为支持抗癌治疗的方法。