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.

Supported phospholipid membrane patches stabilized on graphene surfaces have shown potential in sensor device functionalization, including biosensors and biocatalysis. Lipid dip-pen nanolithography (L-DPN) is a method useful in generating supported membrane structures that maintain lipid functionality, such as exhibiting specific interactions with protein molecules. Here, we have integrated L-DPN, atomic force microscopy, and coarse-grained molecular dynamics simulation methods to characterize the molecular properties of supported lipid membranes (SLMs) on graphene and graphene oxide supports. We observed substantial differences in the topologies of the stabilized lipid structures depending on the nature of the surface (polar graphene oxide vs nonpolar graphene). Furthermore, the addition of water to SLM systems resulted in large-scale reorganization of the lipid structures, with measurable effects on lipid lateral mobility within the supported membranes. We also observed reduced lipid ordering within the supported structures relative to free-standing lipid bilayers, attributed to the strong hydrophobic interactions between the lipids and support. Together, our results provide insight into the molecular effects of graphene and graphene oxide surfaces on lipid bilayer membranes. This will be important in the design of these surfaces for applications such as biosensor devices.

There is urgent need to improve the clinical outcome of peripheral nerve injury. Many efforts are directed towards the fabrication of bioengineered conduits, which could deliver stem cells to the site of injury to promote and guide peripheral nerve regeneration. The aim of this study is to assess whether graphene and related nanomaterials can be useful in the fabrication of such conduits. A comparison is made between graphene oxide (GO) and reduced GO substrates. Our results show that the graphene substrates are highly biocompatible, and the reduced GO substrates are more effective in increasing the gene expression of the biomolecules involved in the regeneration process compared to the other substrates studied.

We report on the adsorption dynamics of phospholipid membranes on graphene-coated substrates using the quartz crystal microbalance with dissipation monitoring (QCM-D) technique. We compare the lipid vescle interaction and membranne formation on gold and silicon dioxide QCM crystal surfaces with their graphene oxide (GO) and reduced (r)GO coated counterparts, and report on the different lipid structures obtained. We establish graphene derivative coatings as support surfaces with tuneable hydrophobicity for the formation of controllable lipid structures. One structure of interest formed are lipid monolayer membrannes which were formed on rGO, which are otherwise challenging to produce. We also demonstrate and monitor biotin-avidin binding on such a membranne, which will then serve as a platform for a wide range of biosensing applications. The QCM-D technique could be extended to both fundamental studies and applications of other covalent and non-covalent interactions in 2-dimensional materials. [7], [8]. Graphene derivatives can solubilize and bind drug molecules and thus have the potential to be drug delivery vehicles [9]. Such properties can be exploited to increase the sensitivity of biosensors [10] and may act as a supporting platform for the construction of biological detection arrays [11], [12]. Graphene oxide (GO) has played an important role in the development of electrochemical [10], [13] and mass-sensitive sensors [14], [15] and inclusively it has shown strong antibacterial activity [16] by affecting the integrity of the cell membrane [17], which is formed by a continuous lipid bilayer. In GO, the main surface functional groups are hydroxyls and epoxies [18], with carboxylic acids and other keto groups on the edges [19]. GO retains sp 2 -carbon domains as well as sp 3 -carbon groups, endowing it with both hydrophobic and hydrophilic domains, respectively [20]. A majority of such functional groups can be removed upon treatment with a reducing agent, such as L-ascorbic acid [21] or hydrazine [22], or thermally [23] to form reduced (r)GO, which is overall significantly more hydrophobic, comparable to pristine graphene. Exploring different routes for the construction of supported lipid membranes (SLMs) (Scheme 1a), such as supported lipid bilayers (SLBs) or monolayers is pertinent since they are useful platforms for the study of fundamental cell functions and signaling, cell-cell interactions, drug delivery and biosensing [24]. SLMs help to establish a model for the cell membrane and can serve as the key component of biosensor devices. The most common membrane lipids are phospholipids; amphiphilic molecules composed of hydrocarbon chain tails attached to a phosphate head group.Here we present the study of the adsorption and rupture of small unilamellar vesicles (SUVs) (typically <100 nm) on GO-and rGOsubstrates, monitored using the quartz crystal microbalance with dissipation monitoring (QCM-D) technique [25]. Substrates used here were produced by spin coating GO on QCM-D crystals. This coating technique i...

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