Graphene-based materials: The missing piece in nanomedicine?

This is the final version. Available on open access from Elsevier via the DOI in this recordNanomedicine utilizes biocompatible nanomaterials for therapeutic as well as imaging purposes for the treatment of various diseases including cancer, neurological disorders and wound infections. Graphene and its modified nanostructures have attracted much attention in recent years in nanomedicine owing to their scalable and cost effective preparation and physiochemical features (high specific surface area, ease in conjugation to peptides/antibodies/proteins and biocompatibility). However, the limited fabrication, functionalization, and in vivo functionalities available in literature indicate inconsistencies regarding the factors affecting in vivo metabolisms, biodistribution as well as toxicity patterns of graphene. It appears that redox signaling pathways, and their proper use to target specific diseases and to improve biocompatibility and interplay between size and optical properties are key determinants to investigate the metabolic fate of such materials. This featured letter provides key insights into the significance and multifunctional roles of redox regulated species in graphene-based materials which can be used to closely mimic therapeutic functions, navigating new paths to nanomedicine and synthetic biology. Furthermore, this letter focuses on the missing functionalities and challenges in using graphene-based materials as both nano-carriers and nano-drugs in various biomedical sectors which might be favorable for multiple payloads and drug targeting in upcoming years.The author acknowledges support from the (Engineering and Physical Sciences Research Council EPSRC) Centre for Doctoral Training in Metamaterials at the University of Exeter, United Kingdom [Grant no. EP/L015331/1]

Multivalent nanomedicines to treat COVID-19: A slow train coming

The high transmission rate and serious consequences of the unprecedented COVID-19 pandemic make it challenging and urgent to identify viral pathogens and understand their intrinsic resistance mechanisms, to pave the way for new approaches to combat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Multivalent interactions are responsible for performing a broad range of biological functions in normal cells, such as cell-cell communication and adhesion. Multivalency underlies the reversibility of ligand-receptor interactions during infections. Previous studies into multivalent nanomedicines used against viruses, have revealed their ability, not only to probe the molecular processes of viral infections, but also to target pathogen-host cell binding with minimal collateral damage to normal cells. Nanomedicines are comparable in size to viruses and to cell receptor complexes (that mediate viral uptake), and can function as safe and accurate armoured vehicles to facilitate the transport of anti-viral drugs. Multivalent nanomedicines can be designed to avoid binding to extracellular serum proteins, and ultimately lead to destruction of the viruses. This brief perspective highlights the potential of innovative smart and safe multivalent nanomedicines that could target multiple viral factors involved in infections at cellular levels. For instance it is possible to target viral spike protein mediated entry pathways, as well as viral replication and cell lysis. Nanomedicine-based approaches could open new opportunities for anti-coronavirus therapies

Developing the next generation of graphene-based platforms for cancer therapeutics: The potential role of reactive oxygen species.

This is the final version of the article. Available from the publisher via the DOI in this record.Graphene has a promising future in applications such as disease diagnosis, cancer therapy, drug/gene delivery, bio-imaging and antibacterial approaches owing to graphene's unique physical, chemical and mechanical properties alongside minimal toxicity to normal cells, and photo-stability. However, these unique features and bioavailability of graphene are fraught with uncertainties and concerns for environmental and occupational exposure. Changes in the physicochemical properties of graphene affect biological responses including reactive oxygen species (ROS) production. Lower production of ROS by currently available theranostic agents, e.g. magnetic nanoparticles, carbon nanotubes, gold nanostructures or polymeric nanoparticles, restricts their clinical application in cancer therapy. Oxidative stress induced by graphene accumulated in living organs is due to acellular factors which may affect physiological interactions between graphene and target tissues and cells. Acellular factors include particle size, shape, surface charge, surface containing functional groups, and light activation. Cellular responses such as mitochondrial respiration, graphene-cell interactions and pH of the medium are also determinants of ROS production. The mechanisms of ROS production by graphene and the role of ROS for cancer treatment, are poorly understood. The aim of this review is to set the theoretical basis for further research in developing graphene-based theranostic platforms.The authors would like to thank the EPSRC CDT in Metamaterials (Grant No. EP/L015331/1 G930207) University of Exeter, United Kingdom, for supporting this work

Rapid and label-free detection of COVID-19 using coherent anti-Stokes Raman scattering microscopy

From the 1918 influenza pandemic (H1N1) until the recent 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, no efficient diagnostic tools have been developed for sensitive identification of viral pathogens. Rigorous, early, and accurate detection of viral pathogens is not only linked to preventing transmission but also to timely treatment and monitoring of drug resistance. Reverse transcription-polymerase chain reaction (RT-PCR), the gold standard method for microbiology and virology testing, suffers from both false-negative and false-positive results arising from the detection limit, contamination of samples/templates, exponential DNA amplification, and variation of viral ribonucleic acid sequences within a single individual during the course of the infection. Rapid, sensitive, and label-free detection of SARS-CoV-2 can provide a first line of defense against the current pandemic. A promising technique is non-linear coherent anti-Stokes Raman scattering (CARS) microscopy, which has the ability to capture rich spatiotemporal structural and functional information at a high acquisition speed in a label-free manner from a biological system. Raman scattering is a process in which the distinctive spectral signatures associated with light-sample interaction provide information on the chemical composition of the sample. In this prospective, we briefly discuss the development and future prospects of CARS for real-time multiplexed label-free detection of SARS-CoV-2 pathogens

Graphene-Based Nanocomposites as Antibacterial, Antiviral and Antifungal Agents

Over the past decade, there have been many interesting studies in the scientific literature about the interaction of graphene-based polymeric nanocomposites with microorganisms to tackle antimicrobial resistance. These studies have reported variable intensities of biocompatibility and selectivity for the nanocomposites toward a specific strain, but it is widely believed that graphene nanocomposites have antibacterial, antiviral, and antifungal activities. Such antibacterial activity is due to several mechanisms by which graphene nanocomposites can act on cells including stimulating oxidative stress; disrupting membranes due to sharp edges; greatly changing core structure mechanical strength and coarseness. However, the underlying mechanisms of graphene nanocomposites as antiviral and antifungal agents remain relatively scarce. In this review, recent advances in the synthesis, functional tailoring, and antibacterial, antiviral, and antifungal applications of graphene nanocomposites are summarized. The synthesis of graphene materials and graphene-based polymeric nanocomposites with techniques such as pressurized gyration, electrospinning, chemical vapor deposition, and layer-by-layer self-assembly is first introduced. Then, the antimicrobial mechanisms of graphene membranes are presented and demonstrated typical in vitro and in vivo studies on the use of graphene nanocomposites for antibacterial, antiviral, and antifungal applications. Finally, the review describes the biosafety, current limitations, and potential of antimicrobial graphene-based nanocomposites

Porous Graphene Composite Polymer Fibres

Since the isolation of graphene, there have been boundless pursuits to exploit the many superior properties that this material possesses; nearing the two-decade mark, progress has been made, but more is yet to be done for it to be truly exploited at a commercial scale. Porous graphene (PG) has recently been explored as a promising membrane material for polymer composite fibres. However, controlling the incorporation of high surface area PG into polymer fibres remain largely unexplored. Additionally, most polymer-graphene composites suffer from low production rates and yields. In this paper, graphene-loaded microfibres, which can be produced at a very high rate and yield have been formed with a carrier polymer, polycaprolactone. For the first time, PG has been incorporated into polymer matrices produced by a high-output manufacturing process and analysed via multiple techniques; scanning electron microscopy (SEM), Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Raman spectra showed that single layer graphene structures were achieved, evidence for which was also backed up by the other techniques. Fibres with an average diameter ranging from 3–8 µm were produced with 3–5 wt% PG. Here, we show how PG can be easily processed into polymeric fibres, allowing for widespread use in electrical and ultrafiltration system

High yield synthesis of graphene quantum dots from biomass waste as a highly selective probe for Fe3+ sensing

Graphene quantum dots (GQDs), a novel type of zero-dimensional fluorescent materials, have gained considerable attention owing to their unique optical properties, size and quantum confinement. However, their high cost and low yield remain open challenges for practical applications. In this work, a low cost, green and renewable biomass resource is utilised for the high yield synthesis of GQDs via microwave treatment. The synthesis approach involves oxidative cutting of short range ordered carbon derived from pyrolysis of biomass waste. The GQDs are successfully synthesised with a high yield of over 84%, the highest value reported to date for biomass derived GQDs. As prepared GQDs are highly hydrophilic and exhibit unique excitation independent photoluminescence emission, attributed to their single-emission fluorescence centre. As prepared GQDs are further modified by simple hydrothermal treatment and exhibit pronounced optical properties with a high quantum yield of 0.23. These modified GQDs are used for the highly selective and sensitive sensing of ferric ions (Fe3+). A sensitive sensor is prepared for the selective detection of Fe3+ ions with a detection limit of as low as 2.5 × 10–6 M. The utilisation of renewable resource along with facile microwave treatment paves the way to sustainable, high yield and cost-effective synthesis of GQDs for practical applications

A facile synthesis of porous graphene for efficient water and wastewater treatment

This is the final version of the article. Available from Springer Nature via the DOI in this record.The use of two-dimensional graphene-based materials in water treatment has recently gained significant attention due to their unique electronic and thermal mobility, high surface area, high mechanical strength, excellent corrosion resistance and tunable surface chemistry. However, the relatively expensive, poor hydrophobicity, low adsorption capacity and recyclability, and complex post-treatment of the most pristine graphene frameworks limit their practical application. Here, we report a facile scalable method to produce highly porous graphene from reduced graphene oxide via thermal treatment without addition of any catalyst or use of any template. Comparing to conventional graphene counterparts, as-prepared porous graphene nanosheets showed evident improvement in hydrophobicity, adsorption capacity, and recyclability, making them ideal candidate materials for water treatment. Superhydrophobic and superoleophilic porous graphene prepared in this work has been demonstrated as effective absorbents for a broad range of ions, oils and organic solvents, exhibiting high selectivity, good recyclability, and excellent absorption capacities > 90%. The synthesis method of porous graphene reported in this paper is easy to implement, low cost and scalable. These attributes could contribute towards efficient and cost-effective water purification and pollution reduction.The authors acknowledge support from the EPSRC Centre for Doctoral Training in Metamaterials at the University of Exeter [Grant no. EP/L015331/1]

Boron nitride nanoscrolls: structure, synthesis, and applications

This is the author accepted manuscriptBoron nitride nanoscrolls (BNS) are open-ended, one-dimensional (1D) nanostructures made by the process of rolling boron nitride nanosheets (BNNS) into a scroll-like morphology. BNS offer a high surface area to volume ratio and possess many unique properties (similar to carbon nanotubes (CNT), carbon nanoscrolls (CNS) and boron nitride nanotubes (BNT)) such as high resistance to oxidation, chemical stability, increased lubrication, high-temperature resistance, electrical insulation, the ability to cap molecules inside and at the ends,and a wide band gap regardless of chirality. Despite these attractive featuresand properties well suited for applications in biotechnology, energy storage, and electronics, the true potential of boron nitride, and BNS as the next ‘miracle material’ is yet to be fully explored. In this critical review, we assess, for the first time, various studies published on the formation, structural and dynamic characteristics of BNS, potential routes for BNS synthesis, and the toxicology of BNS. Finally, the future perspectives of BNS are discussed in view of its unique and exceptional candidacy for many (real-world) applications

Investigating the intracellular bactericidal effects of rifampicin loaded S-protected thiomeric chitosan nanocargoes against Mycobacterium tuberculosis

The antibiotic drug resistance in Mycobacterium tuberculosis (M.tb) is typically associated with immune evasion shared by pathogenic bacterium and intrinsic antimycobacterial drug resistance. These factors significantly contribute to the limited delivery of drugs intracelullary thereby posing an ever-growing threat to mankind. A promising approach to tackle this multi-drug resistance is to use nanocargoes (NCs) based drug delivery approach. The aim of the present study was to develop mannose coated S-protected thiomeric site-specific nanocargoes (MPTCh-NCs) of Rifampicin (Rif) in order to deliver drug locally inside the macrophages. This NCs-based delivery system modifies the macrophage activation states via mannose receptors and endocytosis to alter the macrophage activation state thus providing synergistic antimycobacterial effects. MPTCh-NCs were synthesized by ionic gelation method and assessed for particle size and encapsulation efficiency Moreover, MPTCh-NCs were also investigated in in vitro for drug release, macrophage uptake, buffering potential, Mycothione reductase (MTR) inhibition ability, minimum inhibitory concentration (MIC), phagolysosomal fusion, reactive oxygen species (ROS) production apoptosis and RV 1258 inhibition. The in vivo bioavailability study of MPTCh-NCs was also evaluated in male BALB/c models over a period of 72 h. The optimized MPTCh-NC formulation was nanosized (390 ± 20 nm) with better EE of Rif i.e. 73.68 ± 5.99%. The MPTCh-NCs showed better buffering capacity at different pH ranges, 35.69 folds higher macrophage uptake than Rif with P-gp inhibition potential and pronounced MTR inhibition potential. The MPTCh-NCs exhibited MIC of 16 μg/ml by drug susceptibility testing. Flow cytometric analysis of MPTCh-NCs exhibited, increased apoptosis (33.29%). Real time PCR data suggested enhanced RV 1258 inhibition potential (0.387 fold expression) of the MPTCh-NCs. In vivo results indicated increased bioavailability of MPTCh-NCs (AUC 12.31 folds higher) in comparison to conventional drug Rif. In summary, the observed capacity of the mannose coated S-protected NCs-based approach to deliver therapeutic levels of Rif selectively has potential to improve the therapeutic management against drug resistant tuberculosis