Cytotoxicity assessment of exfoliated MoS2 using primary human mast cells and the progenitor cell-derived mast cell line LAD2.

Molybdenum disulfide is an emerging 2D material with several potential applications in medicine. Therefore, it is crucial to ascertain its biocompatibility. Mast cells are immune cells that are found in many organs and tissues in contact with the extracellular environment, and can be cultured from progenitor cells present in the bone marrow. Given the long period required for differentiation and proliferation of primary mast cells, human mast cell lines have emerged as a tractable model for biological and toxicological studies. Here, we compare two types of industrial MoS2 using CD34+-derived primary human mast cells and the LAD2 cell line. Minimal effects were observed on early-stage activation endpoints such as ß-hexosaminidase release and expression of surface markers of mast cell activation. Transmission electron microscopy revealed limited uptake of the tested materials. Overall, MoS2 was found to be biocompatible, and the LAD2 cell line was validated as a useful in vitro model of mast cells.

Recent Progress on Second Near-Infrared Emitting Carbon Dots in Biomedicine.

Second near-infrared (NIR-II) carbon dots, with absorption or emission between 1000 and 1700 nm, are gaining increasing attention in the biomaterial field due to their distinctive properties, which include straightforward preparation processes, stable photophysical characteristics, excellent biocompatibility, and low cost. As a result, there is a growing focus on the controlled synthesis and modulation of the photochemical and photophysical properties of NIR-II carbon dots, with the aim to further expand their biomedical applications, a current research hotspot. This account aims to provide a comprehensive overview of the recent advancements in NIR-II carbon dots within the biomedical field. The review will cover the following topics: (i) the design, synthesis, and purification of NIR-II carbon dots, (ii) the surface modification strategies, and (iii) the biomedical applications, particularly in the domain of cancer theranostics. Additionally, this account addresses the challenges encountered by NIR-II carbon dots and will outline future directions in the realm of cancer theranostics. By exploring carbon-based NIR-II biomaterials, we can anticipate that this contribution will garner increased attention and contribute to the development of next-generation advanced functional carbon dots, thereby offering enhanced tools and strategies in the biomedical field.

Biocompatible 2D Materials via Liquid Phase Exfoliation.

2D materials (2DMs), such as graphene, transition metal dichalcogenides (TMDs), and black phosphorus (BP), have been proposed for different types of bioapplications, owing to their unique physicochemical, electrical, optical, and mechanical properties. Liquid phase exfoliation (LPE), as one of the most effective up-scalable and size-controllable methods, is becoming the standard process to produce high quantities of various 2DM types as it can benefit from the use of green and biocompatible conditions. The resulting exfoliated layered materials have garnered significant attention because of their biocompatibility and their potential use in biomedicine as new multimodal therapeutics, antimicrobials, and biosensors. This review focuses on the production of LPE-assisted 2DMs in aqueous solutions with or without the aid of surfactants, bioactive, or non-natural molecules, providing insights into the possibilities of applications of such materials in the biological and biomedical fields.

Celebrating Maurizio Prato's Passion, Talent and Imagination.

This Editorial introduces a Special Collection of papers dedicated to Maurizio Prato, featuring prominent examples of his team's efforts to integrate complex frontier research with pioneering achievements in the field of carbon nanostructures and molecular nanoscience.

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective.

Two-dimensional (2D) materials have attracted tremendous interest ever since the isolation of atomically thin sheets of graphene in 2004 due to the specific and versatile properties of these materials. However, the increasing production and use of 2D materials necessitate a thorough evaluation of the potential impact on human health and the environment. Furthermore, harmonized test protocols are needed with which to assess the safety of 2D materials. The Graphene Flagship project (2013-2023), funded by the European Commission, addressed the identification of the possible hazard of graphene-based materials as well as emerging 2D materials including transition metal dichalcogenides, hexagonal boron nitride, and others. Additionally, so-called green chemistry approaches were explored to achieve the goal of a safe and sustainable production and use of this fascinating family of nanomaterials. The present review provides a compact survey of the findings and the lessons learned in the Graphene Flagship.

Structural Transformation of Coassembled Fmoc-Protected Aromatic Amino Acids to Nanoparticles.

Materials made of assembled biomolecules such as amino acids have drawn much attention during the past decades. Nevertheless, research on the relationship between the chemical structure of building block molecules, supramolecular interactions, and self-assembled structures is still necessary. Herein, the self-assembly and the coassembly of fluorenylmethoxycarbonyl (Fmoc)-protected aromatic amino acids (tyrosine, tryptophan, and phenylalanine) were studied. The individual self-assembly of Fmoc-Tyr-OH and Fmoc-Phe-OH in water formed nanofibers, while Fmoc-Trp-OH self-assembled into nanoparticles. Moreover, when Fmoc-Tyr-OH or Fmoc-Phe-OH was coassembled with Fmoc-Trp-OH, the nanofibers were transformed into nanoparticles. UV-vis spectroscopy, Fourier transform infrared spectroscopy, and fluorescence spectroscopy were used to investigate the supramolecular interactions leading to the self-assembled architectures. π-π stacking and hydrogen bonding were the main driving forces leading to the self-assembly of Fmoc-Tyr-OH and Fmoc-Phe-OH forming nanofibers. Further, a mechanism involving a two-step coassembly process is proposed based on nucleation and elongation/growth to explain the structural transformation. Fmoc-Trp-OH acted as a fiber inhibitor to alter the molecular interactions in the Fmoc-Tyr-OH or Fmoc-Phe-OH self-assembled structures during the coassembly process, locking the coassembly in the nucleation step and preventing the formation of nanofibers. This structural transformation is useful for extending the application of amino acid self- or coassembled materials in different fields. For example, the amino acids forming nanofibers could be applied for tissue engineering, while they could be exploited as drug nanocarriers when they form nanoparticles.

Unveiling Liquid-Phase Exfoliation of Graphite and Boron Nitride Using Fluorescent Dyes Through Combined Experiments and Simulations.

Liquid-phase exfoliation (LPE) in aqueous solutions provides a simple, scalable, and green approach to produce 2D materials. By combining atomistic simulations with exfoliation experiments, the interaction between a surfactant and a 2D layer at the molecular scale can be better understood. In this work, two different dyes, corresponding to rhodamine B base (Rbb) and to a phenylboronic acid BODIPY (PBA-BODIPY) derivative, are employed as dispersants to exfoliate graphene and hexagonal boron nitride (hBN) through sonication-assisted LPE. The exfoliated 2D sheets, mostly as few-layers, exhibit good quality and high loading of dyes. Using molecular dynamics (MD) simulations, the binding free energies are calculated and the arrangement of both dyes on the layers are predicted. It has been found that the dyes show a higher affinity toward hBN than graphene, which is consistent with the higher yields of exfoliated hBN. Furthermore, it is demonstrated that the adsorption behavior of Rbb molecules on graphene and hBN is quite different compared to PBA-BODIPY.

Carbon nanotubes targeted to the tumor microenvironment inhibit metastasis in a preclinical model of melanoma.

Despite notable progress in cancer therapy, metastatic diseases continue to be the primary cause of cancer-related mortality. Multi-walled carbon nanotubes (MWCNTs) can enter tissues and cells and interfere with the dynamics of the cytoskeletal nanofilaments biomimetically. This endows them with intrinsic anti-tumoral effects comparable to those of microtubule-binding chemotherapies such as Taxol®. In this study, our focus was on exploring the potential of oxidized MWCNTs in selectively targeting the vascular endothelial growth factor receptor (VEGFR). Our objective was to evaluate their effectiveness in inhibiting metastatic growth by inducing anti-proliferative, anti-migratory, and cytotoxic effects on both cancer and tumor microenvironment cells. Our findings demonstrated a significant reduction of over 80 % in malignant melanoma lung metastases and a substantial enhancement in overall animal welfare following intravenous administration of the targeted biodegradable MWCNTs. Furthermore, the combination of these nanomaterials with the conventional chemotherapy agent Taxol® yielded a remarkable 90 % increase in the antimetastatic effect. These results highlight the promising potential of this combined therapeutic approach against metastatic disease and are of paramount importance as metastasis is responsible for nearly 60,000 deaths each year.

Graphene oxide and bacteria interactions: what is known and what should we expect?

Graphene oxide (GO) and graphene-based materials (GBMs) have gained over the last two decades considerable attention due to their intrinsic physicochemical properties and their applications. Besides, a lot of concern regarding the potential toxicity of GBMs has emerged. One of the aspects of concern is the interactions between GBMs and different environmental compartments, especially indigenous microbial and, in particular, bacterial communities. Recent research showed that GO and GBMs impacted bacterial pure culture or bacterial communities; therefore, these interactions have to be further studied to better understand and assess the fate of these materials in the environment. Here, we present our opinion and hypotheses related to possible degradation mechanisms of GO that can be used by environmental bacteria. This work is the first attempt to deduce and summarize plausible degradation pathways of GO, from structurally similar recalcitrant and toxic compounds, such as polyaromatic hydrocarbons.

Preparation and optimization of agarose or polyacrylamide/amino acid-based double network hydrogels for photocontrolled drug release.

The high water content and biocompatibility of amino-acid-based supramolecular hydrogels have generated growing interest in drug delivery research. Nevertheless, the existing dominant approach of constructing such hydrogels, the exploitation of a single amino acid type, typically comes with several drawbacks such as weak mechanical properties and long gelation times, hindering their applications. Here, we design a near-infrared (NIR) light-responsive double network (DN) structure, containing amino acids and different synthetic or natural polymers, i.e., polyacrylamide, poly(N-isopropylacrylamide), agarose, or low-gelling agarose. The hydrogels displayed high mechanical strength and high drug-loading capacity. Adjusting the ratio of Fmoc-Tyr-OH/Fmoc-Tyr(Bzl)-OH or Fmoc-Phe-OH/Fmoc-Tyr(Bzl)-OH, we could drastically shorten the gelation time of the DN hydrogels at room and body temperatures. Moreover, introducing photothermal agents (graphene oxide, carbon nanotubes, molybdenum disulfide nanosheets, or indocyanine green), we equipped the hydrogels with NIR responsivity. We demonstrated the light-triggered release of the drug baclofen, which is used in severe spasticity treatment. Rheology and stability tests confirmed the positive impact of the polymers on the mechanical strength of the hydrogels, while maintaining good stability under physiological conditions. Overall, our study contributed a novel hydrogel formulation with high mechanical resistance, rapid gel formation, and efficient NIR-controlled drug release, offering new opportunities for biomedical applications.

Electrochemical impedance spectroscopy, another arrow in the arsenal to study the biodegradability of two-dimensional materials.

Carbon nitride (C3N4) is an innovative material with a high potential in many applications including energy storage, catalysis, composites, and biomedicine. C3N4 appears remarkably interesting not only for its properties but also because its simple preparation routes involve low-cost starting materials and reagents. However, there is still a lack of information on its degradability. For this reason, in this study, we evaluate the environmental persistence of C3N4 and its oxidized form by applying the photo-Fenton reaction. The morphological and structural changes of both materials were monitored by transmission electron microscopy and Raman spectroscopy respectively. In addition, electrochemical impedance spectroscopy has been used as an original technique to validate the degradation process of C3N4.

Pulmonary Toxicity of Boron Nitride Nanomaterials Is Aspect Ratio Dependent.

Boron nitride (BN) nanomaterials have drawn a lot of interest in the material science community. However, extensive research is still needed to thoroughly analyze their safety profiles. Herein, we investigated the pulmonary impact and clearance of two-dimensional hexagonal boron nitride (h-BN) nanosheets and boron nitride nanotubes (BNNTs) in mice. Animals were exposed by single oropharyngeal aspiration to h-BN or BNNTs. On days 1, 7, and 28, bronchoalveolar lavage (BAL) fluids and lungs were collected. On one hand, adverse effects on lungs were evaluated using various approaches (e.g., immune response, histopathology, tissue remodeling, and genotoxicity). On the other hand, material deposition and clearance from the lungs were assessed. Two-dimensional h-BN did not cause any significant immune response or lung damage, although the presence of materials was confirmed by Raman spectroscopy. In addition, the low aspect ratio h-BN nanosheets were internalized rapidly by phagocytic cells present in alveoli, resulting in efficient clearance from the lungs. In contrast, high aspect ratio BNNTs caused a strong and long-lasting inflammatory response, characterized by sustained inflammation up to 28 days after exposure and the activation of both innate and adaptive immunity. Moreover, the presence of granulomatous structures and an indication of ongoing fibrosis as well as DNA damage in the lung parenchyma were evidenced with these materials. Concurrently, BNNTs were identified in lung sections for up to 28 days, suggesting long-term biopersistence, as previously demonstrated for other high aspect ratio nanomaterials with poor lung clearance such as multiwalled carbon nanotubes (MWCNTs). Overall, we reveal the safer toxicological profile of BN-based two-dimensional nanosheets in comparison to their nanotube counterparts. We also report strong similarities between BNNTs and MWCNTs in lung response, emphasizing their high aspect ratio as a major driver of their toxicity.

Photocrosslinked Co-Assembled Amino Acid Nanoparticles for Controlled Chemo/Photothermal Combined Anticancer Therapy.

Nanostructures formed from the self-assembly of amino acids are promising materials in many fields, especially for biomedical applications. However, their low stability resulting from the weak noncovalent interactions between the amino acid building blocks limits their use. In this work, nanoparticles co-assembled by fluorenylmethoxycarbonyl (Fmoc)-protected tyrosine (Fmoc-Tyr-OH) and tryptophan (Fmoc-Trp-OH) are crosslinked by ultraviolet (UV) light irradiation. Two methods are investigated to induce the dimerization of tyrosine, irradiating at 254 nm or at 365 nm in the presence of riboflavin as a photo-initiator. For the crosslinking performed at 254 nm, both Fmoc-Tyr-OH and Fmoc-Trp-OH generate dimers. In contrast, only Fmoc-Tyr-OH participates in the riboflavin-mediated dimerization under irradiation at 365 nm. The participation of both amino acids in forming the dimers leads to more stable crosslinked nanoparticles, allowing also to perform further chemical modifications for cancer applications. The anticancer drug doxorubicin (Dox) is adsorbed onto the crosslinked nanoparticles, subsequently coated by a tannic acid-iron complex, endowing the nanoparticles with glutathione-responsiveness and photothermal properties, allowing to control the release of Dox. A remarkable anticancer efficiency is obtained in vitro and in vivo in tumor-bearing mice thanks to the combined chemo- and photothermal treatment.

Applications of graphene-based nanomaterials in drug design: The good, the bad and the ugly.

INTRODUCTION: Graphene-based materials (GBMs) have unique physicochemical properties that make them extremely attractive as platforms for the design of new drugs. Indeed, their bidimensional (2D) morphology, high surface area, mechanical and optical properties, associated to different possibilities for functionalization of their surface, provides opportunities for their use as nanomedicines for drug delivery and/or phototherapies. AREAS COVERED: This opinion paper provides an overview of the current status of GBMs in drug design, with a focus on their therapeutic applications, potential environmental and health risks, and some controversial results. The authors discuss the chemical modifications of GBMs for the treatment of various diseases. The potential toxicity associated with some GBMs is also presented, along with a safe-by-design approach to minimize the risks. Finally, the authors address some issues associated to the use of GBMs in the biomedical field, such as contradictory antibacterial effects, fluorescence quenching and imprecise chemical functionalization. EXPERT OPINION: GBMs are a promising and exciting area of research in drug delivery. It is however important that responsible and safe use of these materials is ensured to fully exploit their advantages and overcome their drawbacks.

Polymyxin B complexation enhances the antimicrobial potential of graphene oxide.

Introduction: The antibacterial activity of graphene oxide (GO) has been widely explored and tested against various pathogenic bacterial strains. Although antimicrobial activity of GO against planktonic bacterial cells was demonstrated, its bacteriostatic and bactericidal effect alone is not sufficient to damage sedentary and well protected bacterial cells inside biofilms. Thus, to be utilized as an effective antibacterial agent, it is necessary to improve the antibacterial activity of GO either by integration with other nanomaterials or by attachment of antimicrobial agents. In this study, antimicrobial peptide polymyxin B (PMB) was adsorbed onto the surface of pristine GO and GO functionalized with triethylene glycol. Methods: The antibacterial effects of the resulting materials were examined by evaluating minimum inhibitory concentration, minimum bactericidal concentration, time kill assay, live/dead viability staining and scanning electron microscopy. Results and discussion: PMB adsorption significantly enhanced the bacteriostatic and bactericidal activity of GO against both planktonic cells and bacterial cells in biofilms. Furthermore, the coatings of PMB-adsorbed GO applied to catheter tubes strongly mitigated biofilm formation, by preventing bacterial adhesion and killing the bacterial cells that managed to attach. The presented results suggest that antibacterial peptide absorption can significantly enhance the antibacterial activity of GO and the resulting material can be effectively used not only against planktonic bacteria but also against infectious biofilms.

Janus porous polylactic acid membranes with versatile metal-phenolic interface for biomimetic periodontal bone regeneration.

Conventional treatment to periodontal and many other bone defects requires the use of barrier membranes to guided tissue regeneration (GTR) and guided bone regeneration (GBR). However, current barrier membranes normally lack of the ability to actively regulate the bone repairing process. Herein, we proposed a biomimetic bone tissue engineering strategy enabled by a new type of Janus porous polylactic acid membrane (PLAM), which was fabricated by combining unidirectional evaporation-induced pore formation with subsequent self-assembly of a bioactive metal-phenolic network (MPN) nanointerface. The prepared PLAM-MPN simultaneously possesses barrier function on the dense side and bone-forming function on the porous side. In vitro, the presence of MPN nanointerface potently alleviated the proinflammatory polarization of mice bone marrow-derived macrophages (BMDMs), induced angiogenesis of human umbilical vein endothelial cells (HUVECs), and enhanced the attachment, migration and osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). The implantation of PLAM-MPN into rat periodontal bone defects remarkably enhanced bone regeneration. This bioactive MPN nanointerface within a Janus porous membrane possesses versatile capacities to regulate cell physiology favoring bone regeneration, demonstrating great potential as GTR and GBR membranes for clinical applications.

Lung Persistence, Biodegradation, and Elimination of Graphene-Based Materials are 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.

RuO2 Nanostructure as an Efficient and Versatile Catalyst for H2 Photosynthesis.

Photocatalytic H2 generation holds promise in the green production of alternative fuels and valuable chemicals. Seeking alternative, cost-effective, stable, and possibly reusable catalysts represents a timeless challenge for scientists working in the field. Herein, commercial RuO2 nanostructures were found to be a robust, versatile, and competitive catalyst in H2 photoproduction in several conditions. We employed it in a classic three-component system and compared its activities with those of the widely used platinum nanoparticle catalyst. We observed a hydrogen evolution rate of 0.137 mol h-1 g-1 and an apparent quantum efficiency (AQE) of 6.8% in water using EDTA as an electron donor. Moreover, the favorable employment of l-cysteine as the electron source opens possibilities precluded to other noble metal catalyst. The versatility of the system has also been demonstrated in organic media with impressive H2 production in acetonitrile. The robustness has been proved by the recovery of the catalyst by centrifugation and reusage alternatively in different media.

Correction to "Bonding of Neuropeptide Y on Graphene Oxide for Drug Delivery Applications to the Central Nervous System".

[This corrects the article DOI: 10.1021/acsanm.2c03409.].