Chemistry of two-dimensional pnictogens: emerging post-graphene materials for advanced applications.

The layered allotropes of group 15 (P, As, Sb and Bi), also called two-dimensional (2D) pnictogens, have emerged as one of the most promising families of post-graphene 2D-materials. This is mainly due to the great variety of properties they exhibit, including layer-dependent bandgap, high charge-carrier mobility and current on/off ratios, strong spin-orbit coupling, wide allotropic diversity and pronounced chemical reactivity. These are key ingredients for exciting applications in (opto)electronics, heterogeneous catalysis, nanomedicine or energy storage and conversion, to name a few. However, there are still many challenges to overcome in order to fully understand their properties and bring them to real applications. As a matter of fact, due to their strong interlayer interactions, the mechanical exfoliation (top-down) of heavy pnictogens (Sb & Bi) is unsatisfactory, requiring the development of new methodologies for the isolation of single layers and the scalable production of high-quality flakes. Moreover, due to their pronounced chemical reactivity, it is necessary to develop passivation strategies, thus preventing environmental degradation, as in the case of bP, or controlling surface oxidation, with the corresponding modification of the interfacial and electronic properties. In this Feature Article we will discuss, among others, the most important contributions carried out in our group, including new liquid phase exfoliation (LPE) processes, bottom-up colloidal approaches, the preparation of intercalation compounds, innovative non-covalent and covalent functionalization protocols or novel concepts for potential applications in catalysis, electronics, photonics, biomedicine or energy storage and conversion. The past years have seen the birth of the chemistry of pnictogens at the nanoscale, and this review intends to highlight the importance of the chemical approach in the successful development of routes to synthesise, passivate, modify, or process these materials, paving the way for their use in applications of great societal impact

Rational chemical multifunctionalization of graphene interface enhances targeted cancer therapy

The synthesis of a drug delivery platform based on graphene was achieved through a step‐by‐step strategy of selective amine deprotection and functionalization. The multifunctional graphene platform, functionalized with indocyanine green, folic acid, and doxorubicin showed an enhanced anticancer activity. The remarkable targeting capacity for cancer cells in combination with the synergistic effect of drug release and photothermal properties prove the great advantage of a combined chemo‐ and phototherapy based on graphene against cancer, opening the doors to future therapeutic applications of this type of material

A Straightforward approach to multifunctional graphene

Graphene has been covalently functionalized through a one‐pot reductive pathway using graphite intercalation compounds (GICs), in particular KC8, with three different orthogonally protected derivatives of 4‐aminobenzylamine. This novel multifunctional platform exhibits excellent bulk functionalization homogeneity (Hbulk) and degree of addition while preserving the chemical functionalities of the organic addends through different protecting groups, namely: tert‐butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz) and phthalimide (Pht). We have employed (temperature‐dependent) statistical Raman spectroscopy (SRS), X‐ray photoelectron spectroscopy (XPS), magic angle spinning solid state 13C NMR (MAS‐NMR), and a characterization tool consisting of thermogravimetric analysis coupled with gas chromatography and mass spectrometry (TG‐GC‐MS) to unambiguously demonstrate the covalent binding and the chemical nature of the different molecular linkers. This work paves the way for the development of smart graphene‐based materials of great interest in biomedicine or electronics, to name a few, and will serve as a guide in the design of new 2D multifunctional materials

Design and preparations of multifunctional nanomaterials for biomedical applications

Le graphène et le nitrure de bore sont des matériaux bidimensionnles présentant des propriétés prometteuses pour les applications biomédicales. L'objectif de ce travail est l'étude de leur biocompatibilité et de leurs applications en tant que transporteurs de médicaments.Nous avons étudié l’exfoliation de ces deux matériaux dans l’eau en utilisant des tensioactifs organiques biocompatibles pour la stabilisation des feuillets. Nous avons obtenu des dispersions stables de celles-ci par bain sonicateur, et sélectionné la taille des feuillets par ultracentrifugation. Enfin, nous avons étudié la cytotoxicité in vitro du graphène et du hBN et la toxicité in vivo du graphène. En outre, nous avons exploré la fonctionnalisation covalente du graphène afin d’obtenir une plate-forme multifonctionnelle pour les applications de délivrance de médicaments. Après la fonctionnalisation covalente de la surface, nous avons introduit différentes fonctionnalités sur la plate-forme, pour le ciblage, le suivi et les applications anticancéreuses du graphène multifonctionnel. Enfin, nous avons étudié les propriétés anticancéreuses du matériau développé sur les cellules HeLa, montrant des résultats prometteurs pour l’application biomédicale de matériaux à base de graphène.Graphene and boron nitride are 2D materials presenting promising properties for biomedical application. Aim of this work is the investigation of their biocompatibility and the applications as drug delivery carriers. We investigated the exfoliation of these two materials in water, employing biocompatible organic surfactants for the stabilization of the sheets. We obtained stable dispersions of these by bath sonication, tailoring the size of the sheets by ultra-centrifugation. Finally, we investigated the in vitro cytotoxicity of graphene and hBN and the in vivo toxicity of graphene. Furthermore, we explored the covalent functionalization of graphene to obtain a multi-functional platform for drug delivery applications. After the covalent functionalization of the surface, we introduced different functionalities on the platform, for the targeting, tracking and anti-cancer applications of multi-functional graphene.Finally, we investigated the anti-cancer properties of the developed material on HeLa cells, showing promising results for biomedical application of graphene-based materials

Mechanics of biosurfactant aided liquid phase exfoliation of 2D materials

Biosurfactant-aided liquid-phase exfoliation (LPE) is emerging as a biocompatible, green, economical, safe, and efficient approach to prepare two-dimensional (2D) materials for biomedical applications. However, relatively little is known about the molecular mechanisms of this process. Herein, we present the first study of how flavin mononucleotide (FMN) interacts with hexagonal boron nitride (hBN) nanosheets in the context of LPE. We demonstrate that FMN molecules can self-assemble on hBN via π-π interactions, as well as intermolecular hydrogen bonds (H-bonds) between the isoalloxazine moieties. Binding free energy analysis has shown FMN to be an efficient surfactant for LPE of hBN in water. According to the theoretical simulations, stable water suspension of hBN were experimentally obtained by LPE using FMN. With this work, we aim to exemplify how molecular dynamics (MD) simulation can predict and guide empirical LPE experiments, direct the surfactant screening and improve scalable production of 2D materials for biomedical applications

Inside Back Cover: Rational Chemical Multifunctionalization of Graphene Interface Enhances Targeted Cancer Therapy

A multifunctional graphene conjugate was designed for cancer treatment, as reported by E. Miyako, A. Bianco, and co-workers in their Communication on page 14034. The image depicts the three regalia–crown, orb, and sword–representing triply chemically modified graphene as the strongest approach for cancer therapy.PNICTOCHEM 804110 (G.A.)PID2019-111742-GA-I00CIDEGENT/2018/001A multifunctional graphene conjugate was designed for cancer treatment, as reported by E. Miyako, A. Bianco, and co-workers in their Communication on page 14034. The image depicts the three regalia–crown, orb, and sword–representing triply chemically modified graphene as the strongest approach for cancer therapy.Es una portada de revista, actividad de difusión

2D Materials and Primary Human Dendritic Cells: A Comparative Cytotoxicity Study

International audienceHuman health can be affected by materials indirectly through exposure to the environment or directly through close contact and uptake. With the ever-growing use of 2D materials in many applications such as electronics, medical therapeutics, molecular sensing, and energy storage, it has become more pertinent to investigate their impact on the immune system. Dendritic cells (DCs) are highly important, considering their role as the main link between the innate and the adaptive immune system. By using primary human DCs, it is shown that hexagonal boron nitride (hBN), graphene oxide (GO) and molybdenum disulphide have minimal effects on viability. In particular, it is evidenced that hBN and GO increase DC maturation, while GO leads to the release of reactive oxygen species and pro-inflammatory cytokines. hBN and MoS2 increase T cell proliferation with and without the presence of DCs. hBN in particular does not show any sign of downstream T cell polarization. The study allows ranking of the three materials in terms of inherent toxicity, providing the following trend: GO > hBN ≈ MoS2, with GO the most cytotoxic

Boron Nitride Nanosheets Can Induce Water Channels Across Lipid Bilayers Leading to Lysosomal Permeabilization

While the interaction between 2D materials and cells is of key importance to the development of nanomedicines and safe applications of nanotechnology, still little is known about the biological interactions of many emerging 2D materials. Here, an investigation of how hexagonal boron nitride (hBN) interacts with the cell membrane is carried out by combining molecular dynamics (MD), liquid-phase exfoliation, and in vitro imaging methods. MD simulations reveal that a sharp hBN wedge can penetrate a lipid bilayer and form a cross-membrane water channel along its exposed polar edges, while a round hBN sheet does not exhibit this behavior. It is hypothesized that such water channels can facilitate cross-membrane transport, with important consequences including lysosomal membrane permeabilization, an emerging mechanism of cellular toxicity that involves the release of cathepsin B and generation of radical oxygen species leading to cell apoptosis. To test this hypothesis, two types of hBN nanosheets, one with a rhomboidal, cornered morphology and one with a round morphology, are prepared, and human lung epithelial cells are exposed to both materials. The cornered hBN with lateral polar edges results in a dose-dependent cytotoxic effect, whereas round hBN does not cause significant toxicity, thus confirming our premise

Lung Persistence, Biodegradation and Elimination of Graphene Based Materials is Predominantly Size-Dependent and Mediated by Alveolar Phagocytes

Graphene-based materials (GBMs) have promising applications in various sectors, including pulmonary nanomedicine. Nevertheless, the influence of GBM physicochemical characteristics on their fate and impact in lung has not been thoroughly addressed. To fill this gap, the biological response, distribution, and bio-persistence of four different GBMs in mouse lungs up to 28 days after single oropharyngeal aspiration are investigated. None of the GBMs, varying in size (large versus small) and carbon to oxygen ratio as well as thickness (few-layers graphene (FLG) versus thin graphene oxide (GO)), induce a strong pulmonary immune response. However, recruited neutrophils internalize nanosheets better and degrade GBMs faster than macrophages, revealing their crucial role in the elimination of small GBMs. In contrast, large GO sheets induce more damages due to a hindered degradation and long-term persistence in macrophages. Overall, small dimensions appear to be a leading feature in the design of safe GBM pulmonary nanovectors due to an enhanced degradation in phagocytes and a faster clearance from the lungs for small GBMs. Thickness also plays an important role, since decreased material loading in alveolar phagocytes and faster elimination are found for FLGs compared to thinner GOs. These results are important for designing safer-by-design GBMs for biomedical application