Abstract
Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy.
Highlights
Primary brain tumors represent about 2% of all malignant tumors in adults; 50%–60% of these are astrocyte gliomas [1]
We demonstrated that graphene enters into GMB cells and other cells in GMB tissue, causing severe destruction of cells by triggering apoptosis
The Fourier transform infrared spectroscopy (FTIR) spectrum of reduced graphene oxide (rGO), rGO + Arg and rGO + Pro samples indicate the presence of amino acids grafted by rGO (Figure 2)
Summary
Primary brain tumors represent about 2% of all malignant tumors in adults; 50%–60% of these are astrocyte gliomas [1]. These tumors are relatively uncommon, they generate major clinical problems because of their infiltrative growth, aggressive character and progression to malignancy [2]. Glioblastoma multiforme (GBM) is extremely aggressive and the most lethal type of brain tumor. After diagnosis the median patient survival is approximately one year [3,4]. Major challenges in the therapy of GBM are associated with the tumor location within the brain, which greatly complicates surgical removal, and the fact that pharmacological therapy is extremely harmful to healthy tissues [5]. Research into new methods for GBM therapy that minimize side effects remains indispensable
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