A possible application of these SGSs is within the medical sector due to their enhanced solubility (compared PD-332991 to other PI3K inhibitor graphene derivatives) and potential for surface modifications for attachment of biomolecules and drugs. However, the interaction of SGSs with biological systems has yet to be investigated and is the basis of the work described herein. To date, much of the biological work regarding graphene has focused on assessing

the cytotoxicity, cell adhesion, proliferation, and antibacterial properties of graphene oxide (GO) [5–8] as well as biodistribution, toxicology, and internalization of various suspensions of GO complexes. These include 125I and 188Re radioisotope-labeled GO [9, 10], PEGylated GO for cellular imaging and delivery of water-insoluble cancer drugs [11–13], and the imaging and treatment of brain, SBI-0206965 in vivo lung,

and breast xenograft tumors in mice through the use of photothermal light therapy from the absorption of near-infrared (NIR) light by PEGylated GO with fluorescent Cy7 probes [14]. Toxicity analysis (in vitro) of GO (prepared using chemical vapor deposition or the modified Hummers method [15]) on lung [16, 17] and neuronal [18] cell lines (A549 and PC12, respectively) has shown concentration-dependent cytotoxicity. The exact mechanism of cell death from GO remains uncertain although a slight increase in lactate dehydrogenase (LDH) from cells, generation of reactive oxygen species, and weak activation of a caspase-3-mediated apoptosis pathway have all been reported. These reports suggest GO cytotoxicity from either direct cellular membrane damage or activation of natural cellular suicide Protirelin mechanisms. Similarly, in vivo mouse toxicology studies have shown that GO nanoplatelets of diameters 10 to 700 nm apparently cause no acute toxicities at low doses [9, 10]. However,

at high doses (10 mg/kg), significant pathological changes such as granulomatous lesions, pulmonary edema, inflammatory cell infiltration, and fibrosis were observed throughout the lungs. In light of the potential applications of graphene materials in drug delivery, imaging, and thermal therapy, but with limitations due to cytotoxicity of GO, we sought to investigate the in vitro interaction of our highly water-soluble SGS with liver cancer cells. Our initial studies using the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), WST-1[2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1), and LDH colorimetric assays have shown that SGSs are non-toxic up to concentrations of 10 μg/ml. We also show that liver cancer cell lines (SNU449 and Hep3B) can internalize SGSs of diameters up to 5 μm, which in some cases are comparable to the size of the cells themselves.