Graphene oxide selectively targets cancer stem cells, across multiple tumor types: Implications for non-toxic cancer treatment, via “differentiation-based nano-therapy”

Abstract

Tumor-initiating cells (TICs), a.k.a. cancer stem cells (CSCs), are difficult to eradicate with conventional approaches to cancer treatment, such as chemo-therapy and radiation. As a consequence, the survival of residual CSCs is thought to drive the onset of tumor recurrence, distant metastasis, and drug-resistance, which is a significant clinical problem for the effective treatment of cancer. Thus, novel approaches to cancer therapy are needed urgently, to address this clinical need. Towards this end, here we have investigated the therapeutic potential of graphene oxide to target cancer stem cells. Graphene and its derivatives are well-known, relatively inert and potentially non-toxic nano-materials that form stable dispersions in a variety of solvents. Here, we show that graphene oxide (of both big and small flake sizes) can be used to selectively inhibit the proliferative expansion of cancer stem cells, across multiple tumor types. For this purpose, we employed the tumor-sphere assay, which functionally measures the clonal expansion of single cancer stem cells under anchorage-independent conditions. More specifically, we show that graphene oxide effectively inhibits tumor-sphere formation in multiple cell lines, across 6 different cancer types, including breast, ovarian, prostate, lung and pancreatic cancers, as well as glioblastoma (brain). In striking contrast, graphene oxide is non-toxic for “bulk” cancer cells (non-stem) and normal fibroblasts. Mechanistically, we present evidence that GO exerts its striking effects on CSCs by inhibiting several key signal transduction pathways (WNT, Notch and STAT-signaling) and thereby inducing CSC differentiation. Thus, graphene oxide may be an effective non-toxic therapeutic strategy for the eradication of cancer stem cells, via differentiation-based nano-therapy.

Graphene and graphene oxide as nanomaterials for medicine and biology application

“…Graphene is used to detect early stage of cancer cells [77]. With the tumour sphere assay, the functionality as well as the clonal expansion of the anchorage-independent single cancer stem cell can be measured [77].…”

“…With the tumour sphere assay, the functionality as well as the clonal expansion of the anchorage-independent single cancer stem cell can be measured [77]. GO restricts the formation of tumour sphere effectively in various cell lines that include ovarian, pancreatic, breast, lung cancers and glioblastoma.…”

Analysis of the cytotoxicity of hierarchical nanoporous graphenic carbon against human glioblastoma grade IV cells

“…After 45 min of sonification, the stock solution (1.0 mg/mL) was diluted to different concentrations (5,10,20,50, and 100 μg/mL) with fresh 1× DMEM. Each sample was measured after 120 s of stabilization at 25°C in three replicates.…”

“…6,7 The results of experiments on various carbon nanomaterials have shown that their diverse behavior in living organisms may be useful in cancer therapy. [8][9][10][11] One of the tested materials was graphene, as previous studies have indicated that it is a very promising nanomaterial in treating glioblastoma. such as graphene oxide and reduced graphene oxide produced by chemical methods, or pristine graphene produced by physical methods, may have different properties.…”

GO/TiO2 Hybrid Nanoparticles as New Photosensitizers in Photodynamic Therapy of A375 Melanoma Cancer Cells

“…For these reasons, GO NPs have been proposed for treatment of cancer (5). As an evidence, Fiorillo et al revealed that GO NPs could eradicate cancer stem cells, offering them as a new therapeutic strategy of cancer (22). Moreover, when GO is co-loaded with a second anti-cancer agent, its anti-cancer properties might be improved (5).…”