Nano-Graphene Oxide for Cellular Imaging and Drug Delivery

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 viaπ-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.

Carbon Nanotubes in Biology and Medicine:In vitro and in vivo Detection,Imaging and Drug Delivery

Carbon nanotubes exhibit many unique intrinsic physical and chemical properties and have been intensively explored for biological and biomedical applications in the past few years.In this comprehensive review,we summarize the main results from our and other groups in this field and clarify that surface functionalization is critical to the behavior of carbon nanotubes in biological systems.Ultrasensitive detection of biological species with carbon nanotubes can be realized after surface passivation to inhibit the non-specific binding of biomolecules on the hydrophobic nanotube surface.Electrical nanosensors based on nanotubes provide a label-free approach to biological detection.Surface-enhanced Raman spectroscopy of carbon nanotubes opens up a method of protein microarray with detection sensitivity down to 1 fmol/L.In vitro and in vivo toxicity studies reveal that highly water soluble and serum stable nanotubes are biocompatible,nontoxic,and potentially useful for biomedical applications.In vivo biodistributions vary with the functionalization and possibly also size of nanotubes,with a tendency to accumulate in the reticuloendothelial system(RES),including the liver and spleen,after intravenous administration.If well functionalized,nanotubes may be excreted mainly through the biliary pathway in feces.Carbon nanotube-based drug delivery has shown promise in various In vitro and in vivo experiments including delivery of small interfering RNA(siRNA),paclitaxel and doxorubicin.Moreover,single-walled carbon nanotubes with various interesting intrinsic optical properties have been used as novel photoluminescence,Raman,and photoacoustic contrast agents for imaging of cells and animals.Further multidisciplinary explorations in this field may bring new opportunities in the realm of biomedicine.

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 1.0-1.4μm emission region and as NIR absorbers and heaters at 808 nm for photothermal tumor elimination at the lowest injected dose(70μg 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 700μg 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.