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.

We report the synthesis of a graphene-sulfur composite material by wrapping polyethyleneglycol (PEG) coated submicron sulfur particles with mildly oxidized graphene oxide sheets decorated by carbon black nanoparticles. The PEG and graphene coating layers are important to accommodating volume expansion of the coated sulfur particles during discharge, trapping soluble polysulfide intermediates and rendering the sulfur particles electrically conducting. The resulting graphene-sulfur composite showed high and stable specific capacities up to ~600mAh/g over more than 100 cycles, representing a promising cathode material for rechargeable lithium batteries with high energy density.

We developed nanosized, reduced graphene oxide (nano-rGO) sheets with high near-infrared (NIR) light absorbance and biocompatibility for potential photothermal therapy. The single-layered nano-rGO sheets were ∼20 nm in average lateral dimension, functionalized noncovalently by amphiphilic PEGylated polymer chains to render stability in biological solutions and exhibited 6-fold higher NIR absorption than nonreduced, covalently PEGylated nano-GO. Attaching a targeting peptide bearing the Arg-Gly-Asp (RGD) motif to nano-rGO afforded selective cellular uptake in U87MG cancer cells and highly effective photoablation of cells in vitro. In the absence of any NIR irradiation, nano-rGO exhibited little toxicity in vitro at concentrations well above the doses needed for photothermal heating. This work established nano-rGO as a novel photothermal agent due to its small size, high photothermal efficiency, and low cost as compared to other NIR photothermal agents including gold nanomaterials and carbon nanotubes.

We develop a simple chemical method to obtain bulk quantities of N-doped, reduced graphene oxide (GO) sheets through thermal annealing of GO in ammonia. X-ray photoelectron spectroscopy (XPS) study of GO sheets annealed at various reaction temperatures reveals that N-doping occurs at a temperature as low as 300ºC, while the highest doping level of ~5% N is achieved at 500ºC. N-doping is accompanied by the reduction of GO with decreases in oxygen levels from ~28% in as-made GO down to ~2% in 1100ºC NH 3 reacted GO. XPS analysis of the N binding configurations of doped GO finds pyridinic N in the doped samples, with increased quaternary N (N that replaced the carbon atoms in the graphene plane) in GO annealed at higher temperatures (>900ºC). Oxygen groups in GO were found responsible for reactions with NH 3 and C-N bond formation.Pre-reduced GO with fewer oxygen groups by thermal annealing in H 2 exhibits greatly reduced reactivity with NH 3 and lower N-doping level.2 Electrical measurements of individual GO sheet devices demonstrate that GO annealed in NH 3 exhibits higher conductivity than those annealed in H 2 , suggesting more effective reduction of GO by annealing in NH 3 than in H 2 , consistent with XPS data. The N-doped reduced GO shows clearly n-type electron doping behavior with Dirac point (DP) at negative gate voltages in three terminal devices. Our method could lead to the synthesis of bulk amounts of N-doped, reduced GO sheets useful for various practical applications.3

We developed two-step solution-phase reactions to form hybrid materials of Mn(3)O(4) nanoparticles on reduced graphene oxide (RGO) sheets for lithium ion battery applications. Selective growth of Mn(3)O(4) nanoparticles on RGO sheets, in contrast to free particle growth in solution, allowed for the electrically insulating Mn(3)O(4) nanoparticles to be wired up to a current collector through the underlying conducting graphene network. The Mn(3)O(4) nanoparticles formed on RGO show a high specific capacity up to ∼900 mAh/g, near their theoretical capacity, with good rate capability and cycling stability, owing to the intimate interactions between the graphene substrates and the Mn(3)O(4) nanoparticles grown atop. The Mn(3)O(4)/RGO hybrid could be a promising candidate material for a high-capacity, low-cost, and environmentally friendly anode for lithium ion batteries. Our growth-on-graphene approach should offer a new technique for the design and synthesis of battery electrodes based on highly insulating materials.

The near-infrared photoluminescence intrinsic to semiconducting single-walled carbon nanotubes is ideal for biological imaging owing to the low autofluorescence and deep tissue penetration in the near-infrared region beyond 1 µm. However, biocompatible single-walled carbon nanotubes with high quantum yield have been elusive. Here, we show that sonicating single-walled carbon nanotubes with sodium cholate, followed by surfactant exchange to form phospholipidpolyethylene glycol coated nanotubes, produces in vivo imaging agents that are both bright and biocompatible. The exchange procedure is better than directly sonicating the tubes with the phospholipid-polyethylene glycol, because it results in less damage to the nanotubes and improves the quantum yield. We show whole-animal in vivo imaging using an InGaAs camera in the 1-1.7 µm spectral range by detecting the intrinsic near-infrared photoluminescence of the 'exchange' single-walled carbon nanotubes at a low dose (17 mg l −1 injected dose). The deep tissue penetration and low autofluorescence background allowed high-resolution intravital microscopy imaging of tumour vessels beneath thick skin.Single-walled carbon nanotubes (SWNTs) have shown potential for biological and medical 1 applications because of their intrinsic optical properties and ability to load both targeting ligands and chemotherapy drugs, in vitro 2,3 and in vivo 4-6. Their unique optical properties make SWNTs attractive candidates for biological imaging7 -11 and sensing12. In particular, the near-infrared (NIR) photoluminescence of semiconducting SWNTs13 has made them promising as NIR fluorescent contrast agents in biological systems8 -11. SWNT NIR fluorescent probes with emission mostly in the infrared-A (IR-A, 1-1.4 µm) region (Fig. 1) are ideal as biological probes because of the inherently low autofluorescence in the NIR range (0.8-1.7 µm) 14 and large Stokes shift between the excitation and emission bands, which allows excitation in the biological transparency window15 near 800 nm while further reducing the background effects of autofluorescence and scattering. Work carried out by Lim and colleagues16 has predicted that NIR fluorophores with emission in the 1,100-1,400 nm range have higher tissue penetration than those near 800 nm by considering the

In vivo real-time epifluorescence imaging of mouse hindlimb vasculatures in the second near-infrared region (NIR-II, 1.1–1.4 µm) is performed using single-walled carbon nanotubes (SWNTs) as fluorophores. Both high spatial resolution (~30 µm) and temporal resolution (<200 ms/frame) for small vessel imaging are achieved 1~3 mm deep in the tissue owing to the beneficial NIR-II optical window that affords deep anatomical penetration and low scattering. This spatial resolution is unattainable by traditional NIR imaging (NIR-I, 0.75–0.9 µm) or microscopic computed tomography (micro-CT), while the temporal resolution far exceeds scanning microscopic imaging techniques. Arterial and venous vessels are unambiguously differentiated using a dynamic contrast-enhanced NIR-II imaging technique based on their distinct hemodynamics. Further, the deep tissue penetration, high spatial and temporal resolution of NIR-II imaging allow for precise quantifications of blood velocity in both normal and ischemic femoral arteries, which are beyond the capability of ultrasonography at lower blood velocity.