Joshua T. Robinson

PEGylated Nanographene Oxide for Delivery of Water-Insoluble Cancer Drugs

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 nanographene 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) analogue, SN38, noncovalently via pi-pi 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.

Mn3O4−Graphene Hybrid as a High-Capacity Anode Material for Lithium Ion Batteries

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.

Graphene-Wrapped Sulfur Particles as a Rechargeable Lithium-Sulfur Battery Cathode Material with High Capacity and Cycling Stability

We report the synthesis of a graphene-sulfur composite material by wrapping poly(ethylene glycol) (PEG) coated submicrometer 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 ∼600 mAh/g over more than 100 cycles, representing a promising cathode material for rechargeable lithium batteries with high energy density.

Simultaneous Nitrogen Doping and Reduction of Graphene Oxide

We developed 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 300 degrees C, while the highest doping level of approximately 5% N is achieved at 500 degrees C. N-doping is accompanied by the reduction of GO with decreases in oxygen levels from approximately 28% in as-made GO down to approximately 2% in 1100 degrees C 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 (> or = 900 degrees C). Oxygen groups in GO were found responsible for reactions with NH(3) and C-N bond formation. Prereduced GO with fewer oxygen groups by thermal annealing in H(2) exhibits greatly reduced reactivity with NH(3) and a lower N-doping level. 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 the 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.

Ultrasmall Reduced Graphene Oxide with High Near-Infrared Absorbance for Photothermal Therapy

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.

Solvothermal Reduction of Chemically Exfoliated Graphene Sheets

We have developed a solvothermal reduction method that affords more effective reduction of chemically derived graphene sheets and graphite oxide than low-temperature reduction methods. Solvothermal reduction removed oxygen and defects from graphene sheets, increased the size of sp(2) domains, and produced materials that were as conducting as pristine graphene and exhibited clear intrinsic Dirac behavior.

Nanocrystal Growth on Graphene with Various Degrees of Oxidation

We show a general two-step method for growing hydroxide and oxide nanocrystals of the iron family elements (Ni, Co, Fe) on graphene with two degrees of oxidation. Drastically different nanocrystal growth behaviors were observed on low-oxidation graphene sheets (GS) and highly oxidized graphite oxide (GO) in hydrothermal reactions. Small particles precoated on GS with few oxygen-containing surface groups diffused and recrystallized into single-crystalline Ni(OH)(2) hexagonal nanoplates or Fe(2)O(3) nanorods with well-defined morphologies. In contrast, particles precoated on GO were pinned by the high-concentration oxygen groups and defects on GO without recrystallization into well-defined shapes. Adjusting the reaction temperature can be included to further control materials grown on graphene. For materials with weak interactions with graphene, increasing the reaction temperature can lead to diffusion and recrystallization of surface species into larger crystals, even on highly oxidized and defective GO. Our results suggest an interesting new approach for controlling the morphology of nanomaterials grown on graphene by tuning the surface chemistry of graphene substrates used for crystal nucleation and growth.

Multifunctional in vivo vascular imaging using near-infrared II fluorescence

In vivo real-time epifluorescence imaging of mouse hind limb vasculatures in the second near-infrared region (NIR-II) is performed using single-walled carbon nanotubes as fluorophores. Both high spatial (∼30 μm) and temporal (<200 ms per frame) resolution for small-vessel imaging are achieved at 1–3 mm deep in the hind limb 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) or microscopic computed tomography, and 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 on the basis of their distinct hemodynamics. Further, the deep tissue penetration and 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 capabilities of ultrasonography at lower blood velocities.

High performance in vivo near-IR (>1 μm) imaging and photothermal cancer therapy with carbon nanotubes

Short single-walled carbon nanotubes (SWNTs) functionalized by PEGylated phospholipids are biologically non-toxic and long-circulating nanomaterials with intrinsic near infrared photoluminescence (NIR PL), characteristic Raman spectra, and strong optical absorbance in the near infrared (NIR). This work demonstrates the first dual application of intravenously injected SWNTs as photoluminescent agents for in vivo tumor imaging in the 1.0–1.4 μm emission region and as NIR absorbers and heaters at 808 nm for photothermal tumor elimination at the lowest injected dose (70 μg of SWNT/mouse, equivalent to 3.6 mg/kg) and laser irradiation power (0.6 W/cm2) reported to date. Ex vivo resonance Raman imaging revealed the SWNT distribution within tumors at a high spatial resolution. Complete tumor elimination was achieved for large numbers of photothermally treated mice without any toxic side effects after more than six months post-treatment. Further, side-by-side experiments were carried out to compare the performance of SWNTs and gold nanorods (AuNRs) at an injected dose of 700 μg of AuNR/mouse (equivalent to 35 mg/kg) in NIR photothermal ablation of tumors in vivo. Highly effective tumor elimination with SWNTs was achieved at 10 times lower injected doses and lower irradiation powers than for AuNRs. These results suggest there are significant benefits of utilizing the intrinsic properties of biocompatible SWNTs for combined cancer imaging and therapy.

Carbon materials for drug delivery & cancer therapy

Carbon nanotubes and graphene are both low-dimensional sp2 carbon nanomaterials exhibiting many unique physical and chemical properties that are interesting in a wide range of areas including nanomedicine. Since 2004, carbon nanotubes have been extensively explored as drug delivery carriers for the intracellular transport of chemotherapy drugs, proteins, and genes. In vivo cancer treatment with carbon nanotubes has been demonstrated in animal experiments by several different groups. Recently, graphene, another allotrope of carbon, has also shown promise in various biomedical applications. In this article, we will highlight recent research on these two categories of closely related carbon nanomaterials for applications in drug delivery and cancer therapy, and discuss the opportunities and challenges in this rapidly growing field.