PEGylated Nanographene Oxide for Delivery of Water-Insoluble Cancer Drugs

PEGylated Nanographene Oxide for Delivery of Water-Insoluble Cancer Drug

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 °C, while the highest doping level of ∼5% N is achieved at 500 °C. N-doping is accompanied by the reduction of GO with decreases in oxygen levels from ∼28% in as-made GO down to ∼2% in 1100 °C NH3 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 (≥900 °C). Oxygen groups in GO were found responsible for reactions with NH3 and C−N bond formation. Prereduced GO with fewer oxygen groups by thermal annealing in H2 exhibits greatly reduced reactivity with NH3 and a lower N-doping level. Electrical measurements of individual GO sheet devices demonstrate that GO annealed in NH3 exhibits higher conductivity than those annealed in H2, suggesting more effective reduction of GO by annealing in NH3 than in H2, 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

Ultra-Low Doses of Chirality Sorted (6,5) Carbon Nanotubes for Simultaneous Tumor Imaging and Photothermal Therapy

Single-walled carbon nanotubes (SWCNTs) exhibit intrinsic fluorescence and strong optical absorption in the near-infrared (NIR) biological window (0.7–1.4 μm), rendering them ideal for <i>in vivo</i> imaging and photothermal therapy. Advances in SWCNT sorting have led to improved nanoelectronics and are promising for nanomedicine. To date, SWCNTs used <i>in vivo</i> consist of heterogeneous mixtures of nanotubes and only a small subset of chirality nanotubes fluoresces or heats under a NIR laser. Here, we demonstrate that separated (6,5) SWCNTs exchanged into a biocompatible surfactant, C₁₈-PMH-mPEG, are more than 6-fold brighter in photoluminescence on the per mass basis, afford clear tumor imaging, and reach requisite photothermal tumor ablation temperatures with a >10-fold lower injected dose than as-synthesized SWCNT mixtures while exhibiting relatively low (6,5) accumulation in the reticuloendothelial system. The intravenous injection of ∼4 μg of (6,5) SWCNTs per mouse (0.254 mg/kg) for dual imaging/photothermal therapy is, by far, the lowest reported dose for nanoparticle-based <i>in vivo</i> therapeutics

Graphite-Coated Magnetic Nanoparticle Microarray for Few-Cells Enrichment and Detection

Graphite-coated, highly magnetic FeCo core–shell nanoparticles were synthesized by a chemical vapor deposition method and solubilized in aqueous solution through a unique polymer mixture modification, which significantly improved the biocompatibility and stability of the magnetic nanoparticles (MNPs). Such functionalized MNPs were proven to be very stable in different conditions which would be significant for biological applications. Cell staining, manipulation, enrichment, and detection were developed with these MNPs. Under external magnetic manipulation, the MNP-stained cells exhibited directed motions. Moreover, MNPs were printed on substrates to modulate the magnetic field distribution on the surface. Capture and detection of sparse populations of cancer cells spiked into whole blood has been explored in a microarray fashion. Cancer cells from hundreds down to only two were able to be simply and efficiently detected from 1 mL of whole blood on the MNP microarray chips. Interestingly, the cells captured through the MNP microarray still showed viability and adhered to the MNP spots after incubation, which could be utilized for cancer cell detection, localized growth, and proliferation

Chirality Enriched (12,1) and (11,3) Single-Walled Carbon Nanotubes for Biological Imaging

The intrinsic band gap photoluminescence of semiconducting single-walled carbon nanotubes (SWNTs) makes them promising biological imaging probes in the second near-infrared (NIR-II, 1.0–1.4 μm) window. Thus far, SWNTs used for biological applications have been a complex mixture of metallic and semiconducting species with random chiralities, preventing simultaneous resonant excitation of all semiconducting nanotubes and emission at a single well-defined wavelength. Here, we developed a simple gel filtration method to enrich semiconducting (12,1) and (11,3) SWNTs with identical resonance absorption at ∼808 nm and emission near ∼1200 nm. The chirality sorted SWNTs showed ∼5-fold higher photoluminescence intensity under resonant excitation of 808 nm than unsorted SWNTs on a per-mass basis. Real-time <i>in vivo</i> video imaging of whole mouse body and tumor vessels was achieved using a ∼6-fold lower injected dose of (12,1) and (11,3) SWNTs (∼3 μg per mouse or ∼0.16 mg/kg of body weight vs 1.0 mg/kg for unsorted SWNTs) than a previous heterogeneous mixture, demonstrating the first resonantly excited and chirality separated SWNTs for biological imaging

Graphite-Coated Magnetic Nanoparticle Microarray for Few-Cells Enrichment and Detection

Graphite-coated, highly magnetic FeCo core–shell nanoparticles were synthesized by a chemical vapor deposition method and solubilized in aqueous solution through a unique polymer mixture modification, which significantly improved the biocompatibility and stability of the magnetic nanoparticles (MNPs). Such functionalized MNPs were proven to be very stable in different conditions which would be significant for biological applications. Cell staining, manipulation, enrichment, and detection were developed with these MNPs. Under external magnetic manipulation, the MNP-stained cells exhibited directed motions. Moreover, MNPs were printed on substrates to modulate the magnetic field distribution on the surface. Capture and detection of sparse populations of cancer cells spiked into whole blood has been explored in a microarray fashion. Cancer cells from hundreds down to only two were able to be simply and efficiently detected from 1 mL of whole blood on the MNP microarray chips. Interestingly, the cells captured through the MNP microarray still showed viability and adhered to the MNP spots after incubation, which could be utilized for cancer cell detection, localized growth, and proliferation