We present the science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems, targeting an evolution in technology, that might lead to impacts and benefits reaching into most areas of society. This roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. We provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large number of sectors, highlighting the steps necessary to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries. We also define an extensive list of acronyms in an effort to standardize the nomenclature in this emerging field.

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Science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems

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 chemi...

Graphene in Mice: Ultrahigh In Vivo Tumor Uptake and Efficient Photothermal Therapy

Functional Nanomaterials for Phototherapies of Cancer

Owing to their unique physical and chemical properties, graphene and its derivatives such as graphene oxide (GO), reduced graphene oxide (RGO) and GO-nanocomposites have attracted tremendous interest in many different fields including biomedicine in recent years. With every atom exposed on its surface, single-layered graphene shows ultra-high surface area available for efficient molecular loading and bioconjugation, and has been widely explored as novel nano-carriers for drug and gene delivery. Utilizing the intrinsic near-infrared (NIR) optical absorbance, in vivo graphene-based photothermal therapy has been realized, achieving excellent anti-tumor therapeutic efficacy in animal experiments. A variety of inorganic nanoparticles can be grown on the surface of nano-graphene, obtaining functional graphene-based nanocomposites with interesting optical and magnetic properties useful for multi-modal imaging and imaging-guided cancer therapy. Moreover, significant efforts have also been devoted to study the behaviors and toxicology of functionalized nano-graphene in animals. It has been uncovered that both surface chemistry and sizes play key roles in controlling the biodistribution, excretion, and toxicity of nano-graphene. Biocompatibly coated nano-graphene with ultra-small sizes can be cleared out from body after systemic administration, without rendering noticeable toxicity to the treated mice. In this review article, we will summarize the latest progress in this rapidly growing field, and discuss future prospects and challenges of using graphene-based materials for theranostic applications.

Nano-graphene in biomedicine: theranostic applications

and Applications of Fullerenes, Carbon Dots, Nanotubes, Graphene, Nanodiamonds, and Combined Superstructures Vasilios Georgakilas,† Jason A. Perman,‡ Jiri Tucek,‡ and Radek Zboril*,‡ †Material Science Department, University of Patras, 26504 Rio Patras, Greece ‡Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University in Olomouc, 17 listopadu 1192/12, 771 46 Olomouc, Czech Republic

Broad family of carbon nanoallotropes: classification, chemistry, and applications of fullerenes, carbon dots, nanotubes, graphene, nanodiamonds, and combined superstructures.

A simple synthetic route for the preparation of functional nanoscale graphene oxide (NGO), a novel nanocarrier for the loading and targeted delivery of anticancer drugs, is reported. The NGO is functionalized with sulfonic acid groups, which render it stable in physiological solution, followed by covalent binding of folic acid (FA) molecules to the NGO, thus allowing it to specifically target MCF-7 cells, human breast cancer cells with FA receptors. Furthermore, controlled loading of two anticancer drugs, doxorubicin (DOX) and camptothecin (CPT), onto the FA-conjugated NGO (FA-NGO) via pi-pi stacking and hydrophobic interactions is investigated. It is demonstrated that FA-NGO loaded with the two anticancer drugs shows specific targeting to MCF-7 cells, and remarkably high cytotoxicity compared to NGO loaded with either DOX or CPT only. Considering that the combined use of two or more drugs, a widely adopted clinical practice, often displays much better therapeutic efficacy than that of a single drug, the controlled loading and targeted delivery of mixed anticancer drugs using these graphene-based nanocarriers may find widespread application in biomedicine.

Functional Graphene Oxide as a Nanocarrier for Controlled Loading and Targeted Delivery of Mixed Anticancer Drugs

PEI GO The RNA interference (RNAi) technique, an effective method to inhibit protein expression by targeted cleavage of messenger RNA (mRNA), has made substantial progress since the fi rst demonstration of gene knockdown in mammalian cells. [ 1 ] Short interfering RNA (siRNA) induces specifi c silencing of targeted protein, thus offering signifi cant potential in overcoming multiple drug resistance (MDR) of cancer cells. [ 2 ] For example, Bcl-2 protein, one of the main antiapoptotic defense proteins, is closely related to the MDR of cancer cells. [ 3 ] Knockdown of the Bcl-2 protein expression level in cancer cells by Bcl-2-targeted siRNA would effectively overcome the MDR of cancer cells and sensitize cancer cells to anticancer drugs. [ 3 d, 4 ] Herein, we report sequential delivery of Bcl-2-targeted siRNA and the anticancer drug doxorubicin (DOX) using polyethylenimine (PEI)-functionalized graphene oxide (PEI-GO). We demonstrate that the PEI-GO is an excellent nanocarrier for effective delivery of siRNA and chemical drugs, and that sequential delivery of the siRNA and DOX by PEI-GO into cancer cells exhibits a synergistic effect, which leads to a signifi cantly enhanced chemotherapy effi cacy. To the best of our knowledge, this is the fi rst report on applications of GO-based nanovectors for delivery of siRNA, and sequential delivery of siRNA and anticancer drugs into cancer cells. Graphene, a newly discovered 2D nanomaterial, has been studied extensively due to its fundamental importance and potential applications, [ 5 ] while exploration of its biomedical applications has just started. [ 6 ] Noncovalent adsorption through π – π stacking, electrostatic, and other molecular interactions has proven to be effective for immobilizing chemical drugs, single-stranded DNA, and RNA onto GO sheets. [ 6 a–e]

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Enhanced Chemotherapy Efficacy by Sequential Delivery of siRNA and Anticancer Drugs Using PEI‐Grafted Graphene Oxide

Single stranded ribonucleic acid (ssRNA) acts as a probe, antisense (AS), miRNA analog and inhibitor, and is promising for gene therapy and molecular diagnosis. However, free ssRNA exhibits poor cellular uptake due to its negative charges, and enzyme instability, which have largely limited the practical applications of ssRNA in biomedicine. To address these issues, we have developed a PEGylated reduced graphene oxide (PEG-RGO) nanovector for efficient delivery of ssRNA. We have demonstrated that PEG-RGO exhibits superior ssRNA loading and delivery capability, compared to the widely studied PEGylated graphene oxide (PEG-GO). Computational simulation further suggested that PEG-RGO binds ssRNA much stronger than PEG-GO, consistent with the experimental results. These results will have implications in designing RGO-based biocompatible and efficient ssRNA delivery systems.

Qinghuan Zhao

Papers

Functional Graphene Oxide as a Nanocarrier for Controlled Loading and Targeted Delivery of Mixed Anticancer Drugs

Enhanced Chemotherapy Efficacy by Sequential Delivery of siRNA and Anticancer Drugs Using PEI‐Grafted Graphene Oxide

PEGylated reduced graphene oxide as a superior ssRNA delivery system

Self-assembled virus-like particles from rotavirus structural protein VP6 for targeted drug delivery.

Rotavirus capsid surface protein VP4-coated Fe3O4 nanoparticles as a theranostic platform for cellular imaging and drug delivery