Graphene quantum dots (GQD), the new generation members of graphene-family, have shown promising applications in anticancer therapy. In this study, we report the synthesis of a fluorescent and biocompatible nanovector, based on GQD, for the targeted delivery of an anticancer drug with benzofuran structure (BFG) and bearing the targeting ligand riboflavin (RF, vitamin B2). The highly water-dispersible nanoparticles, synthesized from multi-walled carbon nanotubes (MWCNT) by prolonged acidic treatment, were linked covalently to the drug by means of a cleavable PEG linker while the targeting ligand RF was conjugated to the GQD by π–π interaction using a pyrene linker. The cytotoxic effect of the synthesized drug delivery system (DDS) GQD-PEG-BFG@Pyr-RF was tested on three cancer cell lines and this effect was compared with that exerted by the same nanovector lacking the RF ligand (GQD-PEG-BFG) or the anticancer drug (GQD@Pyr-RF). The results of biological tests underlined the low cytotoxicity of the GQD sample and the cytotoxic activity of the DDS against the investigated cancer cell lines with a higher or similar potency to that exerted by the BFG alone, thus opening new possibilities for the use of this drug or other anticancer agents endowed of cytotoxicity and serious side effects.

Graphene quantum dots (GQDs), the latest member of the graphene family, have attracted enormous interest in the last few years, due to their exceptional physical, chemical, electrical, optical, and biological properties. Their strong size‐dependent photoluminescence and the presence of many reactive groups on the graphene surface allow their multimodal conjugation with therapeutic agents, targeting ligands, polymers, light responsive agents, fluorescent dyes, and functional nanoparticles, making them valuable agents for cancer diagnosis and treatment. In this review, the very recent advances covering the last 3 years on the applications of GQDs as drug delivery systems and theranostic tools for anticancer therapy are discussed, highlighting the relevant factors which regulate their biocompatibility. Among these factors, the size, kind, and degree of surface functionalization have shown to greatly affect their use in biological systems. Toxicity issues, which still represent an open challenge for the clinical development of GQDs based therapeutic agents, are also discussed at cellular and animal levels.

The timely diagnosis of cancer represents the best chance to increase treatment success and to reduce cancer deaths. Nanomaterials-based biosensors containing graphene quantum dots (GQDs) as a sensing platform show great promise in the early and sensitive detection of cancer biomarkers, due to their unique chemical and physical properties, large surface area and ease of functionalization with different biomolecules able to recognize relevant cancer biomarkers. In this review, we report different advanced strategies for the synthesis and functionalization of GQDs with different agents able to selectively recognize and convert into a signal specific cancer biomarkers such as antigens, enzymes, hormones, proteins, cancer related byproducts, biomolecules exposed on the surface of cancer cells and changes in pH. The developed optical, electrochemical and chemiluminescent biosensors based on GQDs have been shown to ensure the effective diagnosis of several cancer diseases as well as the possibility to evaluate the effectiveness of anticancer therapy. The wide linear range of detection and low detection limits recorded for most of the reported biosensors highlight their great potential in clinics for the diagnosis and management of cancer.

Due to their outstanding physicochemical properties, the next generation of the graphene family—graphene quantum dots (GQDs)—are at the cutting edge of nanotechnology development. GQDs generally possess many hydrophilic functionalities which allow their dispersibility in water but, on the other hand, could interfere with reactions that are mainly performed in organic solvents, as for cycloaddition reactions. We investigated the 1,3-dipolar cycloaddition (1,3-DCA) reactions of the C-ethoxycarbonyl N-methyl nitrone 1a and the newly synthesized C-diethoxyphosphorylpropilidene N-benzyl nitrone 1b with the surface of GQDs, affording the isoxazolidine cycloadducts isox-GQDs 2a and isox-GQDs 2b. Reactions were performed in mild and eco-friendly conditions, through the use of a natural deep eutectic solvent (NADES), free of chloride or any metal ions in its composition, and formed by the zwitterionic trimethylglycine as the -bond acceptor, and glycolic acid as the hydrogen-bond donor. The results reported in this study have for the first time proved the possibility of performing cycloaddition reactions directly to the p-cloud of the GQDs surface. The use of DES for the cycloaddition reactions on GQDs, other than to improve the solubility of reactants, has been shown to bring additional advantages because of the great affinity of these green solvents with aromatic systems.

Cancer-targeted drug delivery systems (DDS) based on carbon nanostructures have shown great promise in cancer therapy due to their ability to selectively recognize specific receptors overexpressed in cancer cells. In this paper, we have explored a green route to synthesize nanobiochar (NBC) endowed with graphene structure from the hydrothermal carbonization (HTC) of orange peels and evaluated the suitability of this nanomaterial as a nanoplatform for cancer therapy. In order to compare the cancer-targeting ability of different widely used targeting ligands (TL), we have conjugated NBC with biotin, riboflavin, folic acid and hyaluronic acid and have tested, in vitro, their biocompatibility and uptake ability towards a human alveolar cancer cell line (A549 cells). The nanosystems which showed the best biological performances—namely, the biotin- and riboflavin- conjugated systems—have been loaded with the poorly water-soluble drug DHF (5,5-dimethyl-6a-phenyl-3-(trimethylsilyl)-6,6a-dihydrofuro[3,2-b]furan-2(5H)-one) and tested for their anticancer activity. The in vitro biological tests demonstrated the ability of both systems to internalize the drug in A549 cells. In particular, the biotin-functionalized NBC caused cell death percentages to more than double with respect to the drug alone. The reported results also highlight the positive effect of the presence of oxygen-containing functional groups, present on the NBC surface, to improve the water dispersion stability of the DDS and thus make the approach of using this nanomaterial as nanocarrier for poorly water-soluble drugs effective.