CHARACTERIZATION, FUNCTIONALIZATION AND BIOLOGICAL EVALUATION OF CARBON NANOSTRUCTURES

Carbon nanostructures are gaining attention due to their promising properties for a wide range of applications from electrochromic devices to drug nanocarriers. Among the members of carbon nanostructure family, nanodiamonds (NDs), graphene quantum dots (GQDs), carbon dots (CDs) and multi-walled carbon nanotubes (MWCNTs) were used in this research project. Different functionalization reactions were performed on carbon nanostructures and the obtained products were characterized and evaluated. Rhamnose, imidazolium containing ionic liquids, 2-(2-(2-(2-aminoethoxy)ethoxy)ethyl)isoindoline-1,3-dione and tert-butyl (2-(2-(2-aminoethoxy)ethoxy)ethyl)carbamate were some organic molecules used for functionalizations in order to improve the solubility of carbon nanostructures and add different physical, electronic and biological properties. Despite promising properties, nanodiamonds tend to create big aggregates in aqueous media and this is the main obstacle for biological applications. It was shown that NDs with proper functionalizations can be dispersed in water and create stable dispersions. Thanks to fluorescent labeling with fluorescein isothiocyanate, NDs have been demonstrated to be promising nanocarrier for the delivery of functionalized molecules on their surface. The functionalization reactions of NDs were performed with different methodologies. NDs were demonstrated to be a performance tuning additive in electrochromic devices. Graphene Quantum Dots were produced with a methodology developed by the research group. Different modifications were performed in order to improve the production. GQDs were functionalized with different organic molecules with different methodologies such as amide bond generation and cycloaddition. It was demonstrated that GQDs have big potential to improve the performance of electrochromic devices. Carbon dots were produced from natural chitin resources: insect exoskeleton and shell of shrimp. It is shown that CDs produced from these natural and renewable resources are strongly fluorescent. CDs obtained from the new production methodology were characterized. Two different types of MWCNTs were functionalized and characterized for the comparison with other carbon nanostructures. The functionalization reactions were optimized in order to obtain high degree of functionalization. New physical, biological and electronic properties were introduced to carbon nanostructures through various functionalization reactions. Graphene quantum dots and carbon dots were produced by using new methodologies. Characterization studies were performed with different techniques, such as TGA, AFM and Raman spectroscopy. Nanodiamonds were evaluated in human peripheral blood mononuclear cells for biomedical applications. Graphene quantum dots and nanodiamonds were evaluated in electrochromic devices for possible performance improvements

Graphene quantum dots : from efficient preparation to safe renal excretion

Carbon nanomaterials offer excellent prospects as therapeutic agents, and among them, graphene quantum dots (GQDs) have gained considerable interest thanks to their aqueous solubility and intrinsic fluorescence, which enable their possible use in theranostic approaches, if their biocompatibility and favorable pharmacokinetic are confirmed. We prepared ultra-small GQDs using an alternative, reproducible, top-down synthesis starting from graphene oxide with a nearly 100% conversion. The materials were tested to assess their safety, demonstrating good biocompatibility and ability in passing the ultrafiltration barrier using an in vitro model. This leads to renal excretion without affecting the kidneys. Moreover, we studied the GQDs in vivo biodistribution confirming their efficient renal clearance, and we demonstrated that the internalization mechanism into podocytes is caveolae-mediated. Therefore, considering the reported characteristics, it appears possible to vehiculate compounds to kidneys by means of GQDs, overcoming problems related to lysosomal degradation

Graphene, other carbon nanomaterials and the immune system:toward nanoimmunity-by-design

Carbon-based materials (CBMs), such as graphene, nanodiamonds, carbon fibers, and carbon dots, have attracted a great deal scientific attention due to their potential as biomedical tools. Following exposure, particularly intravenous injection, these nanomaterials can be recognized by immune cells. Such interactions could be modulated by the different physicochemical properties of the materials (e.g. structure, size, and chemical functions), by either stimulating or suppressing the immune response. However, a harmonized cutting-edge approach for the classification of these materials based not only on their physicochemical parameters but also their immune properties has been missing. The European Commission-funded G-IMMUNOMICS and CARBO-IMmap projects aimed to fill this gap, developing a functional pipeline for the qualitative and quantitative immune characterization of graphene, graphene-related materials (GRMs), and other CBMs. The goal was to open breakthrough perspectives for the definition of the immune profiles of these materials. Here, we summarize our methodological approach, key results, and the necessary multidisciplinary expertise ranging across various fields, from material chemistry to engineering, immunology, toxicology, and systems biology. G-IMMUNOMICS, as a partnering project of the Graphene Flagship, the largest scientific research initiative on graphene worldwide, also complemented the studies performed in the Flagship on health and environmental impact of GRMs. Finally, we present the nanoimmunity-by-design concept, developed within the projects, which can be readily applied to other 2D materials. Overall, the G-IMMUNOMICS and CARBO-IMmap projects have provided new insights on the immune impact of GRMs and CBMs, thus laying the foundation for their safe use and future translation in medicine