Kostiantyn Turcheniuk

Recent advances in the synthesis of fluorinated aminophosphonates and aminophosphonic acids

This review article surveys recent achievements in the preparation and biological properties evaluation of fluorinated aminophosphonates and aminophosphonic acids. Recently, in view of various important biological applications of the fluorinated aminophosphonic acid derivatives, the development of suitable synthetic methodologies for their preparation in racemic and in optically pure form has been a topic of great interest. Considerable progress has been made in asymmetric synthesis of fluorinated acyclic aminophosphonates and aminophosphonic acids using catalytic enantioselective reduction of fluorinated α-iminophosphonates, catalytic enantioselective addition of alkyl phosphites to fluorinated imines, and diastereoselective addition of alkyl phosphites to chiral fluorinated imines. A new efficient access to CF3-substituted cyclic α-aminophosphonates has been developed based on metal-catalyzed carbene transfer reactions with diethyl 1-diazo-2,2,2-trifluoroethylphosphonate. New processes, e.g. enantioselective alkynylation and nucleophilic aromatic substitution involving fluorinated substrates are also considered.

Gold–graphene nanocomposites for sensing and biomedical applications

Recent developments in materials science and nanotechnology have propelled the development of a plethora of materials with unique chemical and physical properties for biomedical applications. Graphitic nanomaterials such as carbon nanotubes, fullerenes and, more recently, graphene oxide (GO) and reduced graphene oxide (rGO) have received a great deal of interest in this domain. Besides the exceptional physico-chemical features of these materials, another advantage is that they can be easily produced in good quantities. Moreover, the presence of abundant functional groups on their surface and good biocompatibility make them highly suitable for biomedical applications. Many research groups have utilized GO and rGO nanocargos to effectively deliver insoluble drugs, nucleic acids and other molecules into cells for bioimaging and therapeutic purposes. Gold nanostructures (Au NSs), on the other hand, have also attracted great attention owing to their applications in biomedical fields, organic catalysis, etc. Loading of GO and rGO sheets with Au NSs generates a new class of functional materials with improved properties and thus provides new opportunities in the use of such hybrid materials for catalytic biosensing and biomedical applications. This review article is aimed at providing an insight into the important features of gold-graphene nanocomposites, the current research activities related to the different synthetic routes to produce these nanocomposites, and their potential applications in sensing and biomedical therapy, notably photothermal therapy (PTT).

Plasmonic photothermal destruction of uropathogenic E. coli with reduced graphene oxide and core/shell nanocomposites of gold nanorods/reduced graphene oxide

The development of non-antibiotic based treatments against bacterial infections by Gram-negative uropathogenic E. coli is a complex task. New strategies to treat such infections are thus urgently needed. This report illustrates the development of pegylated reduced graphene oxide nanoparticles (rGO-PEG) and gold nanorods (Au NRs) coated with rGO-PEG (rGO-PEG-Au NRs) for the selective killing of uropathogenic E. coli UTI89. We took advantage of the excellent light absorption properties of rGO-PEG and Au NR particles in the near-infrared (NIR) region to photothermally kill Gram-negative pathogens up to 99% in 10 min by illumination of solutions containing the bacteria. The rGO-PEG-Au NRs demonstrated better photothermal efficiency towards E. coli than rGO-PEG. Targeted killing of E. coli UTI89 could be achieved with rGO-PEG-Au NRs functionalized with multimeric heptyl α-d-mannoside probes. This currently offers a unique biocompatible method for the ablation of pathogens with the opening of probably a new possibility for clinical treatments of patients with urinary infections.

Cobalt phthalocyanine tetracarboxylic acid modified reduced graphene oxide: a sensitive matrix for the electrocatalytic detection of peroxynitrite and hydrogen peroxide

The quantification of peroxynitrite (ONOO−, PON) and hydrogen peroxide (H2O2) is intrinsically difficult as both species show similar oxidative features located within a narrow potential. The sub-second lifetime of ONOO− at neutral pH further complicates the analysis. In this paper, we examine the electrocatalytic activity of cobalt phthalocyanine tetracarboxylic acid (CoPc–COOH) loaded reduced graphene oxide (rGO) films towards peroxynitrite and hydrogen peroxide detection. The rGO/CoPc–COOH matrix is synthesized by the reaction of graphene oxide (GO) and CoPc–COOH at 90 °C for 5 h under ultrasonication. The integration of CoPc–COOH and the reduction of GO to rGO was confirmed by X-ray photoelectron spectroscopy, FTIR, Raman, UV-vis spectroscopy and electrochemistry. The rGO/CoPc–COOH film showed high electrocatalytic activity and specificity for ONOO− at anodic potential with a sensitivity of ≈11.5 ± 1 nA nM−1 and a peroxynitrite detection limit of ≈1.7 nM. The rGO/CoPc–COOH films further exhibited electrocatalytic reduction of H2O2 with a sensitivity of 14.5 μA mM−1 and a detection limit of ≈60 μM for H2O2.

Insulin loaded iron magnetic nanoparticle–graphene oxide composites: synthesis, characterization and application for in vivo delivery of insulin

One of the focal subjects in insulin delivery is the development of insulin formulations that protect the native insulin from degradation under acidic pH in the stomach. In this work we show, for the first time, that a graphene oxide (GO) based matrix can ensure the stability of insulin at low pH. GO and GO modified with 2-nitrodopamine coated magnetic particle (GO–MPdop) matrices loaded with insulin were prepared and the pH triggered release of the insulin was studied. The loading of insulin on the GO nanomaterials proved to be extremely high at pH < 5.4 with a loading capacity of 100 ± 3% on GO and 88 ± 3% on GO–MPdop. The insulin-containing GO matrices were stable at acidic pH, while insulin was released when exposed to basic solutions (pH = 9.2). Using Xenopus laevis oocytes as a model we showed that the meiotic resumption rate of GO and GO–MPdop remained unaltered when pre-treated in acidic conditions, while pre-incubated insulin (without GO nanomaterials) has lost almost entirely its maturation effect. These results suggest that GO based nanomatrices are promising systems for the protection of insulin.

Plasmonic photothermal cancer therapy with gold nanorods/reduced graphene oxide core/shell nanocomposites

Gold nanorods (Au NRs) are known for their efficient conversion of photon energy into heat, resulting in hyperthermia and suppression of tumor growth in vitro and in vivo. Au NRs are thus of great promise for photothermal therapy (PTT) of different cancers. From the point of cancer therapy, low laser powers are essential (≤1 W cm−2) to ensure minimal side effects such as skin burning. Herein, we investigate the potential of polyethylene glycol functionalized reduced graphene oxide (rGO-PEG) enrobed Au NRs for the photothermal destruction of human glioblastoma astrocytoma (U87MG) cells in mice. We show that Au NRs@rGO-PEG are ideal multifunctional theranostic nanostructures that can exert efficient photothermal destruction of tumors in mice upon low doses of NIR light excitation and can act as fluorescent cellular markers due to the presence of a NIR dye integrated onto the rGO shell. Due to the specific interaction between Tat protein modified Au NRs@rGO-PEG nanostructures with the human glioblastoma astrocytoma (U87MG) cells, selective targeting of the tumor is achieved. In vivo experiments in mice show that upon irradiation of the tumor implanted in mice at 800 nm under low doses (0.7 W cm−2), U87MG tumor growth gets suppressed. The study demonstrates that the novel nanomaterials allow for an efficient destruction of solid tumors and might thus serve as an excellent multi-functional theranostic agent in photothermal therapeutic applications.

Infrared Photothermal Therapy with Water Soluble Reduced Graphene Oxide: Shape, Size and Reduction Degree Effects

In this work, we investigate the effects of lateral size and reduction level of polyethylene glycol (PEG)-modified graphene oxide (GO) nanosheets on the photothermal properties. PEG-modified GO (GO–PEG) and reduced graphene oxide (rGO–PEG) matrices were synthesized through amide bond formation between the carboxyl groups of carboxylated GO and rGO and the amine groups of a PEG linker. We found that the reaction temperature has an important influence on the morphology and size of the pegylated nanostructures. While rGO–PEG formed at 80°C is of nanometer size, the GO–PEG, prepared at room temperature, has needle-like shape with micrometric dimensions. The rGO–PEG matrix was found to be highly soluble under physiological conditions with no aggregation observed even after 6 months of storage. The cytotoxicity of both matrices as well as their photothermal properties to ablate cervical HeLa cancer cells and MDA-MB-231 human breast carcinoma cells were studied. There was no sign of acute toxicity of rGO–PEG for HeLa and MDA-MB-31 cancer cells over a wide concentration range. A complete destruction of the tumor cells could be achieved with a laser power of 6 W cm-2 and a concentration of 60 μg mL-1 of rGO–PEG.

Particle-based photodynamic therapy based on indocyanine green modified plasmonic nanostructures for inactivation of a Crohn's disease-associated Escherichia coli strain

Particle-based photodynamic therapy (PPDT) holds great promise in theranostic applications. Herein, we demonstrate that PPDT based on gold nanorods coated with an indocyanine green (ICG)-loaded silica shell allows for the inactivation of the Crohns disease-associated adherent-invasive Escherichia coli strain LF82 (E. coli LF82) under pulsed laser light irradiation at 810 nm. Fine-tuning of the plasmonic structures together with maximizing the photosensitizer loading onto the nanostructures allowed optimizing the singlet oxygen generation capability and the PPDT efficiency. Using a nanoparticle concentration low enough to suppress photothermal heating effects, 6 log10 reduction in E. coli LF82 viability could be achieved using gold nanostructures displaying a plasmonic band at 900 nm. An additional modality of nanoparticle-based photoinactivation of E. coli is partly observed, with 3 log10 reduction of bacterial viability using Au NRs@SiO2 without ICG, due to the two-photon induced formation of reactive oxygen species. Interaction of the particles with the bacterial surface, responsible for the disruption of the bacterial integrity, together with the generation of moderate quantities of singlet oxygen could account for this behavior.

Reduced graphene oxide nanosheets decorated with AuPd bimetallic nanoparticles: a multifunctional material for photothermal therapy of cancer cells

Gold nanoparticles (Au NPs) and reduced graphene oxide (rGO) mediated hyperthermia are the two most widely explored systems used for the photothermal ablation of cancer cells. We show that the photothermal conversion and efficiency of these nanomaterials can be improved not only by combining them into one material, but also by forming bimetallic AuPd embedded on rGO. The AuPd NPs-rGO nanocomposites were prepared by a simple one-step chemical reduction technique using the individual metallic salts, graphene oxide (GO) and ascorbic acid as a green reducing agent. The AuPd NPs-rGO nanocomposites were covalently functionalized with poly(ethylene glycol) (PEG) chains and characterized by high resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and UV/Vis spectrophotometry. Covalent attachment of PEG units to the AuPd NPs-rGO nanocomposites greatly improved the solubility and stability of the nanocomposites in biological media and ensured its biocompatibility towards cancer cells such as HeLa cells. The near-infrared photothermal properties of AuPd NPs-rGO-PEG nanocomposites were evaluated using a continuous laser at 800 nm with power densities between 0.5 and 2 W cm-2. The nanocomposite was successfully used for the in vitro photothermal ablation of HeLa cells. At 1 W cm-2, the total killing of HeLa cells was achieved through irradiation of AuPd NPs-rGO-PEG nanocomposites incubated cells for 10 min at a particle concentration of 20 μg mL-1. Such high efficiency was principally assigned to the synergetic effects of rGO and AuPd NPs.