It is known that many potent, often aromatic drugs are water insoluble, which has hampered their use for disease treatment. In this work, we functionalized nano-graphene oxide (NGO), a novel graphitic material, with branched polyethylene glycol (PEG) to obtain a biocompatible NGO-PEG conjugate stable in various biological solutions, and used them for attaching hydrophobic aromatic molecules including a camptothecin (CPT) analog, SN38 non-covalently via π-π stacking. The resulting NGO-PEG-SN38 complex exhibited excellent water solubility while maintaining its high cancer cell killing potency similar to that of the free SN38 molecules in organic solvents. The efficacy of NGO-PEG-SN38 was far higher than that of irinotecan (CPT-11), a FDA approved water soluble SN38 prodrug used for the treatment of colon cancer. Our results showed that graphene is a novel class of material promising for biological applications including future in vivo cancer treatment with various aromatic, low-solubility drugs.Graphene has emerged as a 2D material with interesting physical properties. 1,2 Intensive research is on-going to investigate the quantum physics in this system and potential applications for nano-electronic devices 2 , transparent conductors and nano-composite materials 3 . Thus far, little has been done to explore graphene in biological systems, despite much effort in the area of carbon nanotubes for in vitro and in vivo biological applications. 4-9 Here, we synthesize and functionalize nanoscale graphene oxide (NGO) sheets (<50nm) by branched, biocompatible polyethylene glycol (PEG) to render high aqueous solubility and stability in physiological solutions including serum. We then uncover a unique ability of graphene in attaching and delivery of aromatic, water insoluble drugs.It is known that clinical use of various potent, hydrophobic molecules (many of them aromatic) is often hampered by their poor water solubility. Although synthesis of water soluble pro-drugs may circumvent the problem, the efficacy of the drug decreases. Here, we show that PEGylated NGO (NGO-PEG) readily complexes with a water insoluble aromatic molecule SN38, a camptothecin (CPT) analog, 10 via non-covalent van der Waals interaction. The NGO-PEG-SN38 complex exhibits excellent aqueous solubility and retains the high potency of free SN38 dissolved in organic solvents. The toxicity exceeds that of irinotecan (CPT-11, a FDA approved SN38 prodrug for colon cancer treatment) by 2-3 orders of magnitude.We prepared graphene oxide by oxidizing graphite using a modified Hummer's method. 3,11 The resulting GO (single layered and few-layered, Supp Info. Fig.S1) was soluble in water but aggregated in solutions rich in salts or proteins such as cell medium and serum (Fig. 1a). This was likely due to screening of the electrostatic charges and non-specific binding of proteins on the GO. 12 To impart aqueous stability and prevent bio-fouling, we sonicated the GO to make them into small pieces and conjugated a 6-armed PEG-amine stars to the carboxylic acid...

Two-dimensional graphene offers interesting electronic, thermal, and mechanical properties that are currently being explored for advanced electronics, membranes, and composites. Here we synthesize and explore the biological applications of nano-graphene oxide (NGO), i.e., single-layer graphene oxide sheets down to a few nanometers in lateral width. We develop functionalization chemistry in order to impart solubility and compatibility of NGO in biological environments. We obtain size separated pegylated NGO sheets that are soluble in buffers and serum without agglomeration. The NGO sheets are found to be photoluminescent in the visible and infrared regions. The intrinsic photoluminescence (PL) of NGO is used for live cell imaging in the near-infrared (NIR) with little background. We found that simple physisorption via π-stacking can be used for loading doxorubicin, a widely used cancer drug onto NGO functionalized with antibody for selective killing of cancer cells in vitro. Owing to its small size, intrinsic optical properties, large specifi c surface area, low cost, and useful non-covalent interactions with aromatic drug molecules, NGO is a promising new material for biological and medical applications.

Although biomedical applications of carbon nanotubes have been intensively studied in recent years, its sister, graphene, has been rarely explored in biomedicine. In this work, for the first time we study the in vivo behaviors of nanographene sheets (NGS) with polyethylene glycol (PEG) coating by a fluorescent labeling method. In vivo fluorescence imaging reveals surprisingly high tumor uptake of NGS in several xenograft tumor mouse models. Distinctive from PEGylated carbon nanotubes, PEGylated NGS shows several interesting in vivo behaviors including highly efficient tumor passive targeting and relatively low retention in reticuloendothelial systems. We then utilize the strong optical absorbance of NGS in the near-infrared (NIR) region for in vivo photothermal therapy, achieving ultraefficient tumor ablation after intravenous administration of NGS and low-power NIR laser irradiation on the tumor. Furthermore, no obvious side effect of PEGylated NGS is noted for the injected mice by histology, blood chemistry, and complete blood panel analysis in our pilot toxicity study. Although a lot more efforts are required to further understand the in vivo behaviors and the long-term toxicology of this new type of nanomaterials, our work is the first success of using carbon nanomaterials for efficient in vivo photothermal therapy by intravenous administration and suggests the great promise of graphene in biomedical applications, such as cancer treatment.

All wrapped up: Carbon‐encapsulated metal nanoparticles, carbon microspheres decorated with metal nanoparticles, and particles with layered structures are all accessible by means of a method based on hydrothermal treatment of glucose, which produces monodisperse colloidal carbon microspheres with reactive surfaces. The picture shows silver‐cored carbon spheres obtained by using silver nanoparticles as seeds.

We show that large surface areas exist for supramolecular chemistry on single-walled carbon nanotubes (SWNTs) prefunctionalized noncovalently or covalently by common surfactant or acid-oxidation routes. Water-soluble SWNTs with poly(ethylene glycol) (PEG) functionalization via these routes allow for surprisingly high degrees of pi-stacking of aromatic molecules, including a cancer drug (doxorubicin) with ultrahigh loading capacity, a widely used fluorescence molecule (fluorescein), and combinations of molecules. Binding of molecules to nanotubes and their release can be controlled by varying the pH. The strength of pi-stacking of aromatic molecules is dependent on nanotube diameter, leading to a method for controlling the release rate of molecules from SWNTs by using nanotube materials with suitable diameter. This work introduces the concept of "functionalization partitioning" of SWNTs, i.e., imparting multiple chemical species, such as PEG, drugs, and fluorescent tags, with different functionalities onto the surface of the same nanotube. Such chemical partitioning should open up new opportunities in chemical, biological, and medical applications of novel nanomaterials.