Many new drugs have low aqueous solubility and high therapeutic efficacy. Paclitaxel (PTX) is a classic example of this type of compound. Here we show that extremely small (<40 nm) hydrophilic carbon clusters (HCCs) that are PEGylated (PEG-HCCs) are effective drug delivery vehicles when simply mixed with paclitaxel. This formulation of PTX sequestered in PEG-HCCs (PTX/PEG-HCCs) is stable for at least twenty weeks. The PTX/PEG-HCCs formulation was as effective as PTX in a clinical formulation in reducing tumor volumes in an orthotopic murine model of oral squamous cell carcinoma. Preliminary toxicity and biodistribution studies suggest that the PEG-HCCs are not acutely toxic and, like many other nanomaterials, are primarily accumulated in the liver and spleen. This work demonstrates that carbon nanomaterials are effective drug delivery vehicles in vivo when non-covalently loaded with an unmodified drug.

On page 4008, in the section titled "Synthesis of CDϪgraphene OrganicϪinorganic Hybrid Nanosheets and Pure Graphene", the sixth line reads "mixed with 20.0 mL of 80 mg/mL ␣-, ␤-, or ␥-CD aqueous solution" but should be changed to read "mixed with 20.0 mL of ␣-, ␤-, or ␥-CD (80 mg) aqueous solution".

Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. We previously demonstrated that poly(ethylene glycol)-functionalized carbon nanovectors are able to sequester paclitaxel, a widely used hydrophobic cancer drug, by simple physisorption and deliver the drug for killing of cancer cells. The cell-killing when these drug-loaded carbon nanoparticles were used was equivalent to when a commercial formulation of paclitaxel was used. Here we show that by further mixing the drug-loaded nanoparticles with Cetuximab, a monoclonal antibody that recognizes the epidermal growth factor receptor (EGFR), paclitaxel is preferentially targeted to EGFR+ tumor cells in vitro. This supports progressing to in vivo studies. Moreover, the construct is unusual in that all three components are assembled through non-covalent interactions. Such non-covalent assembly could enable high-throughput screening of drug/antibody combinations.

The aim of this study was to broaden the relatively small number of qualitative and quantitative data available on the endothelium of human blood vessels by scanning electron microscopy (SEM) imaging and computer based image analysis of the human endothelial microstructure and dimensions. Endothelium of the arterial blood vessels (common iliac artery and hepatic artery) was imaged directly by using SEM. From high quality images, precise information on the microstructure and dimensions of endothelial cells was obtained by using GIMP and Leica QWin image analysis software. The mean endothelial cell width, length, and area of common iliac artery endothelial cells were found to be 13.2 ± 4.1 µm, 25.8 ± 8.5 µm, and 245.0 ± 115.1 µm2, respectively. For hepatic artery endothelial cells, mean values of cell width, length, and area were found to be 4.9 ± 1.5 µm, 21.9 ± 6.6 µm, and 70.7 ± 34.8 µm2, respectively. Morphology and dimension of the endothelial cells were different depending on the donor, type, and diameter of the arteries due to the effect of blood flow direction and volume rate. The presented method is useful for obtaining quantitative data on human endothelial cells. This study provides a first basis for future studies with larger numbers of samples on morphological changes secondary to pathological conditions, such as hypertension and atherosclerosis. Furthermore, the data may support the development of a template for a novel artificial vascular graft with superior performance.

No abstract

Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. In an in vitro system, we previously demonstrated that targeted drug delivery to cancer cells overexpressing epidermal growth factor receptor (EGFR+) can be achieved by poly(ethylene glycol)-functionalized carbon nanovectors simply mixed with a drug, paclitaxel, and an antibody that binds to the epidermal growth factor receptor, Cetuximab. This construct is unusual in that all three components are assembled through non-covalent interactions. Here we show that this same construct is effective in vivo, enhancing radiotherapy of EGFR+ tumors. This targeted nanovector system has the potential to be a new therapy for head and neck squamous cell carcinomas, deserving of further preclinical development.

No abstract