Kasturi Muthoosamy

Exceedingly biocompatible and thin-layered reduced graphene oxide nanosheets using an eco-friendly mushroom extract strategy

Purpose A simple, one-pot strategy was used to synthesize reduced graphene oxide (RGO) nanosheets by utilizing an easily available over-the-counter medicinal and edible mushroom, Ganoderma lucidum. Methods The mushroom was boiled in hot water to liberate the polysaccharides, the extract of which was then used directly for the reduction of graphene oxide. The abundance of polysaccharides present in the mushroom serves as a good reducing agent. The proposed strategy evades the use of harmful and expensive chemicals and avoids the typical tedious reaction methods. Results More importantly, the mushroom extract can be easily separated from the product without generating any residual byproducts and can be reused at least three times with good conversion efficiency (75%). It was readily dispersible in water without the need of ultrasonication or any surfactants; whereas 5 minutes of ultrasonication with various solvents produced RGO which was stable for the tested period of 1 year. Based on electrochemical measurements, the followed method did not jeopardize RGO’s electrical conductivity. Moreover, the obtained RGO was highly biocompatible to not only colon (HT-29) and brain (U87MG) cancer cells, but was also viable towards normal cells (MRC-5). Conclusion Besides being eco-friendly, this mushroom based approach is easily scalable and demonstrates remarkable RGO stability and biocompatibility, even without any form of functionalization.

Site-Selective Lysine Modification of Native Proteins and Peptides via Kinetically Controlled Labeling

The site-selective modification of the proteins RNase A, lysozyme C, and the peptide hormone somatostatin is presented via a kinetically controlled labeling approach. A single lysine residue on the surface of these biomolecules reacts with an activated biotinylation reagent at mild conditions, physiological pH, and at RT in a high yield of over 90%. In addition, fast reaction speed, quick and easy purification, as well as low reaction temperatures are particularly attractive for labeling sensitive peptides and proteins. Furthermore, the multifunctional bioorthogonal bioconjugation reagent (19) has been achieved allowing the site-selective incorporation of a single ethynyl group. The introduced ethynyl group is accessible for, e.g., click chemistry as demonstrated by the reaction of RNase A with azidocoumarin. The approach reported herein is fast, less labor-intensive and minimizes the risk for protein misfolding. Kinetically controlled labeling offers a high potential for addressing a broad range of native proteins and peptides in a site-selective fashion and complements the portfolio of recombinant techniques or chemoenzymatic approaches.

State of the art and recent advances in the ultrasound-assisted synthesis, exfoliation and functionalization of graphene derivatives

Sonochemistry, an almost a century old technique was predominantly employed in the cleaning and extraction processes but this tool has now slowly gained tremendous attention in the synthesis of nanoparticles (NPs) where particles of sub-micron have been produced with great stability. Following this, ultrasonication techniques have been largely employed in graphene synthesis and its dispersion in various solvents which would conventionally take days and offers poor yield. Ultrasonic irradiation allows the production of thin-layered graphene oxide (GO) and reduced graphene oxide (RGO) of up to 1nm thickness and can be produced in single layers. With ultrasonic treatment, reactions were made easy whereby graphite can be directly exfoliated to graphene layers. Oxidation to GO can also be carried out within minutes and reduction to RGO is possible without the use of any reducing agents. In addition, various geometry of graphene can be produced such as scrolled graphene, sponge or foam graphene, smooth as well as those with rough edges, each serving its own unique purpose in various applications such as supercapacitor, catalysis, biomedical, etc. In ultrasonic-assisted reaction, deposition of metal NPs on graphene was more homogeneous with custom-made patterns such as core-shell formation, discs, clusters and specific deposition at the edges of graphene sheets. Graphene derivatives with the aid of ultrasonication are the perfect catalyst for various organic reactions as well as an excellent adsorbent. Reactions which used to take hours and days were significantly reduced to minutes with exceedingly high yields. In a more recent approach, sonophotocatalysis was employed for the combined effect of sonication and photocatalysis of metal deposited graphene. The system was highly efficient in organic dye adsorption. This review provides detailed fundamental concepts of ultrasonochemistry for the synthesis of graphene, its dispersion, exfoliation as well as its functionalization, with great emphasis only based on recent publications. Necessary parameters of sonication such as frequency, power input, sonication time, type of sonication as well as temperature and dual-frequency sonication are discussed in great length to provide an overview of the resultant graphene products.

Exceedingly Higher co-loading of Curcumin and Paclitaxel onto Polymer-functionalized Reduced Graphene Oxide for Highly Potent Synergistic Anticancer Treatment

Metastasis of lung carcinoma to breast and vice versa accounts for one of the vast majority of cancer deaths. Synergistic treatments are proven to be the effective method to inhibit malignant cell proliferation. It is highly advantageous to use the minimum amount of a potent toxic drug, such as paclitaxel (Ptx) in ng/ml together with a natural and safe anticancer drug, curcumin (Cur) to reduce the systemic toxicity. However, both Cur and Ptx suffer from poor bioavailability. Herein, a drug delivery cargo was engineered by functionalizing reduced graphene oxide (G) with an amphiphilic polymer, PF-127 (P) by hydrophobic assembly. The drugs were loaded via pi-pi interactions, resulting in a nano-sized GP-Cur-Ptx of 140 nm. A remarkably high Cur loading of 678 wt.% was achieved, the highest thus far compared to any other Cur nanoformulations. Based on cell proliferation assay, GP-Cur-Ptx is a synergistic treatment (CI < 1) and is highly potent towards lung, A549 (IC50 = 13.24 μg/ml) and breast, MDA-MB-231 (IC50 = 1.450 μg/ml) cancer cells. These positive findings are further confirmed by increased reactive oxygen species, mitochondrial membrane potential depletion and cell apoptosis. The same dose treated on normal MRC-5 cells shows that the system is biocompatible and cancerous cell-specific.

Sonochemical and sustainable synthesis of graphene-gold (G-Au) nanocomposites for enzymeless and selective electrochemical detection of nitric oxide

In this study, a sonochemical approach was utilised for the development of graphene-gold (G-Au) nanocomposite. Through the sonochemical method, simultaneous exfoliation of graphite and the reduction of gold chloride occurs to produce highly crystalline G-Au nanocomposite. The in situ growth of gold nanoparticles (AuNPs) took place on the surface of exfoliated few-layer graphene sheets. The G-Au nanocomposite was characterised by UV-vis, XRD, FTIR, TEM, XPS and Raman spectroscopy techniques. This G-Au nanocomposite was used to modify glassy carbon electrode (GCE) to fabricate an electrochemical sensor for the selective detection of nitric oxide (NO), a critical cancer biomarker. G-Au modified GCE exhibited an enhanced electrocatalytic response towards the oxidation of NO as compared to other control electrodes. The electrochemical detection of NO was investigated by linear sweep voltammetry analysis, utilising the G-Au modified GCE in a linear range of 10-5000μM which exhibited a limit of detection of 0.04μM (S/N=3). Furthermore, this enzyme-free G-Au/GCE exhibited an excellent selectivity towards NO in the presence of interferences. The synergistic effect of graphene and AuNPs, which facilitated exceptional electron-transfer processes between the electrolyte and the GCE thereby improving the sensing performance of the fabricated G-Au modified electrode with stable and reproducible responses. This G-Au nanocomposite introduces a new electrode material in the sensitive and selective detection of NO, a prominent biomarker of cancer.

The biogenic synthesis of a reduced graphene oxide–silver (RGO–Ag) nanocomposite and its dual applications as an antibacterial agent and cancer biomarker sensor

Cancer nanotechnology encourages cutting edge research utilizing nanomaterials for the diagnosis, therapy and prevention of cancer. Recognition of cancer-related biomarkers in the body has made early detection possible and thus, paves the way towards devising methods to control it from progressing to advanced stages. Hydrogen peroxide (H2O2) is a critical biomolecule, which plays an important dual role in cancer progression. Herein, we have developed a sensitive method for the detection of H2O2 utilizing a reduced graphene oxide–silver (RGO–Ag) nanocomposite. This RGO–Ag nanocomposite was prepared using a green and facile one-step synthesis approach utilizing the extract of a medicinal mushroom, Ganoderma lucidum. The higher content of polysaccharides in this extract makes it a potent reducing agent for the combined reduction of GO and AgNO3 to produce the RGO–Ag nanocomposite. The properties of the RGO–Ag obtained were characterized by UV-Vis spectroscopy, SEM, TEM, XRD, FT-IR and XPS techniques. The RGO–Ag modified electrode showed good electrocatalytic activity towards H2O2 when compared to other modified electrodes. Furthermore, it showed an LOD of 136 nM, which was determined using the LSV technique. The amperometric i–t curve displayed two different linear ranges of 1–100 μM and 100–1100 μM with an LOD of 3 and 56 nM, respectively. This excellent electrochemical performance towards H2O2 detection could contribute to advances in current cancer diagnosis. The RGO–Ag nanocomposite was also explored as a potential antibacterial agent. Owing to its synergistic effects, RGO–Ag showed a comparable antibacterial activity to the standard antibiotic, chloramphenicol. The combined antibacterial effects and sensing potential make this RGO–Ag nanocomposite a promising candidate for future health care.

Acoustic cavitation induced generation of stabilizer-free, extremely stable reduced graphene oxide nanodispersion for efficient delivery of paclitaxel in cancer cells

Graphene is one of the highly explored nanomaterials due to its unique and extraordinary properties. In this study, by utilizing a hydrothermal reduction method, graphene oxide (GO) was successfully converted to reduced graphene oxide (RGO) without using any toxic reducing agents. Following this, with the use of ultrasonic cavitation, profoundly stable few layer thick RGO nanodispersion was generated without employing any stabilizers or surfactants. During ultrasonication, shockwaves from the collapse of bubbles cause a higher dispersing energy to the graphene nanosheets which surpass the forces of Van der Waals and π-π stacking and thus pave the way to form a stable aqueous nanodispersion of graphene. Ultrasonication systems with different power intensity have been employed to determine the optimum conditions for obtaining the most stable RGO dispersion. The optimised conditions of ultrasonic treatments led to the development of a very stable reduced graphene oxide (RGO) aqueous dispersion. The stability was observed for two years and was analyzed by using Zetasizer by measuring the particle size and zeta potential at regular intervals and found to have exceptional stability. The excellent stability at physiological pH promotes its utilization in nano drug delivery application as a carrier for Paclitaxel (Ptx), an anticancer drug. The in vitro cytotoxicity analysis of Ptx loaded RGO nanodispersion by MTT assay performed on the cell lines revealed the potential of the nanodispersion as a suitable drug carrier. Studies on normal lung cells, MRC-5 and nasopharyngeal cancer cells, HK-1 supported the biocompatibility of RGO-Ptx towards normal cell line. This investigation shows the potential of exceptionally stable RGO-Ptx nanodispersion in nano drug delivery applications.

Conjugation of insulin onto the sidewalls of single-walled carbon nanotubes through functionalization and diimide-activated amidation

Purpose The high aspect ratio of carbon nanotubes (CNTs) allows the attachment of compounds that enhance the functionality of the drug vehicle. Considering this, use of CNTs as a multifunctional insulin carrier may be an interesting prospect to explore. Materials and methods The carboxylic acid groups were functionalized on the sidewalls of single-walled CNTs (SWCNTs) followed by diimidation to form amide bonds with the amine groups of the insulin. Results Scanning transmission electron microscopy and transmission electron microscopy establish clear conjugation of insulin onto the surface of nanotube sidewalls. The incorporation of insulin further increased the solubility of SWCNTs in biological solution for the tested period of 5 months. Bicinchoninic acid assay confirms that 0.42 mg of insulin could be attached to every 1 mg of carboxylated SWCNTs. Conclusion With the successful conjugation of insulin to SWCNTs, it opens up the potential use of SWCNTs as an insulin carrier which in need of further biological studies.

Hydration or hydroxylation: direct synthesis of fullerenol from pristine fullerene [C60] via acoustic cavitation in the presence of hydrogen peroxide

A green and clean approach that requires low energy and avoids the use of any toxic or corrosive reagents/solvents for the synthesis of potential fullerenol moieties [C60(OH)n·mH2O] was proposed in this investigation, in which pristine fullerene (C60) in dil. H2O2 (30%) aqueous media was ultrasonicated (20 kHz, 200 W) at 30% amplitude for 1 h. The attachment of hydroxyl groups (–OH) was investigated via FTIR and the quantification of –OH groups attached to the C60 cage was conducted via elemental analysis. The number of secondary bound water molecules (mH2O) with each fullerenol molecule [C60(OH)n] was measured via TGA, and the estimated average structure of fullerenol was calculated to be C60(OH)8·2H2O. The synthesized fullerenol was moderately soluble in water and DMSO. Furthermore, the size of the synthesized C60(OH)8·2H2O particles determined by both AFM and DLS analysis was found to be in the range of 135–155 nm. The proposed ultrasound-assisted acoustic cavitation technique encompasses a one-step facile reaction strategy, requires less time for the reaction, and reduces the number of solvents required for the separation and purification of C60(OH)8·2H2O, which could be scalable for the commercial synthesis of fullerenol moieties in the future.

Nanomedicine in Theranostics

Theranostics is a novel concept which involves the integration of diagnosis and therapy in a single platform using nanomaterials. Nanotheranostics is a promising combination of multidisciplinary fields like chemistry, physics, material sciences, nanotechnology, drug delivery, and pharmacology. By using innumerable biomarkers, imaging agents, chemotherapeutic agents, and specific targeting ligands, these multidisciplinary theranostic systems will make a radical change in the field of personalized medicine. It enables the simultaneous analysis of diagnostics tests and real-time monitoring of drug effects. This combination therapy can provide optimized treatment for individuals and in the early detection of various diseases. Enhanced drug efficiency, better disease management, and improved healthcare are the different impacts experienced by the various in vitro and in vivo evaluations of nanotheranostic agents. This chapter deals with the basics and applications of nanotheranostics. Besides, it gives an outlook on the future prospects and challenges especially in the field of cancer treatment. Looking into the potential, nanotheranostics devotes an auspicious future in the field of nanomedicine.