Fluorescently Labeled Gadolinium Ferrate/Trigadolinium Pentairon(III) Oxide Nanoparticles: Synthesis, Characterization, In Vivo Biodistribution, and Application for Visualization of Myocardial Ischemia-Reperfusion Injury.

Various gadolinium compounds have been proposed as contrasting agents for magnetic resonance imaging (MRI). In this study, we suggested a new synthesis method of gadolinium ferrate/trigadolinium pentairon(III) oxide nanoparticles (GF/TPO NPs). The specific surface area of gadolinium ferrate (GdFeO3) and trigadolinium pentairon(III) oxide (Gd3Fe5O12) nanoparticles was equal to 42 and 66 m2/g, respectively. The X-ray diffraction analysis confirmed that the synthesized substances were GdFeO3 and Gd3Fe5O12. The gadolinium content in the samples was close to the theoretically calculated value. The free gadolinium content was negligible. Biodistribution of the GF/TPO NPs was studied in rats by fluorescent imaging and Fe2+/Fe3+ quantification demonstrating predominant accumulation in such organs as lung, kidney, and liver. We showed in the in vivo rat model of myocardial ischemia-reperfusion injury that GF/TPO NPs are able to target the area of myocardial infarction as evidenced by the significantly greater level of fluorescence. In perspective, the use of fluorescently labeled GF/TPO NPs in multimodal imaging may provide basis for high-resolution 3D reconstruction of the infarcted heart, thereby serving as unique theranostic platform.

The Combination of Solid-State Chemistry and Medicinal Chemistry as the Basis for the Synthesis of Theranostics Platforms.

This review presents the main patterns of synthesis for theranostics platforms. We examine various approaches to the interpretation of theranostics, statistics of publications drawn from the PubMed database, and the solid-state and medicinal chemistry methods used for the formation of nanotheranostic objects. We highlight and analyze chemical methods for the modification of nanoparticles, synthesis of spacers with functional end-groups, and the immobilization of medicinal substances and fluorophores. An overview of the modern solutions applied in various fields of medicine is provided, along with an outline of specific examples and an analysis of modern trends and development areas of theranostics as a part of personalized medicine.

Graphene Oxide of Extra High Oxidation: A Wafer for Loading Guest Molecules.

We present a new modification of graphene oxide with very high content (85 wt %) of oxygen-containing functional groups (hydroxy, epoxy, lactol, carboxyl, and carbonyl groups) that forms stable aqueous dispersion in up to 9 g·L-1 concentration solutions. A novel faster method of the synthesis is described that produces up to 1 kg of the material and allows controlling the particle size in solution. The synthesized compound was characterized by various physicochemical methods and molecular dynamics modeling, revealing a unique structure in the form of a multilayered wafer of several sheets thick, where each sheet is highly corrugated. The ragged structure of the sheets forms pockets with hindered mobility of water that leads to the possibility of trapping guest molecules.

Biocompatibility of a nanocomposite based on Aerosil 380 and carboxylated fullerene C60[C(COOH)2]3.

Silica is silicon dioxide, which, depending on the production method, can exist in various amorphous forms with varying specific surface area, particle size, pore volume and size, and, as a result, with different physicochemical and sorption characteristics. The presence of silanol groups on the surface of silicas provides the possibility of its further functionalisation. In addition, the developed specific surface of Aerosil allows to obtain composites with a high content of biologically active substances. In this work, we studied the biocompatibility of a composite based on Aerosil 380 and carboxylated fullerene C60[C(COOH)2]3, namely: haemolysis (spontaneous and photoinduced), platelet aggregation, binding to HSA, cyto- and genotoxicity, antiradical activity. Interest in the creation of this nanomaterial is due to the fact that carboxylated fullerenes have potential applications in various fields of biomedicine, including the ability to bind reactive oxygen species, inhibition of tumour development, inactivation of viruses and bacteria. The obtained composite can be used for the immobilisation of various drugs and the further development of drugs for theranostics.

Biological Safety and Biodistribution of Chitosan Nanoparticles.

: The effect of unmodified chitosan nanoparticles with a size of ~100 nm and a weakly positive charge on blood coagulation, metabolic activity of cultured cardiomyocytes, general toxicity, biodistribution, and reactive changes in rat organs in response to their single intravenous administration at doses of 1, 2, and 4 mg/kg was studied. Chitosan nanoparticles (CNPs) have a small cytotoxic effect and have a weak antiplatelet and anticoagulant effect. Intravenous administration of CNPs does not cause significant hemodynamic changes, and 30 min after the CNPs administration, they mainly accumulate in the liver and lungs, without causing hemolysis and leukocytosis. The toxicity of chitosan nanoparticles was manifested in a dose-dependent short-term delay in weight gain with subsequent recovery, while in the 2-week observation period no signs of pain and distress were observed in rats. Granulomas found in the lungs and liver indicate slow biodegradation of chitosan nanoparticles. In general, the obtained results indicate a good tolerance of intravenous administration of an unmodified chitosan suspension in the studied dose range.

A chemiluminescence method for screening of fluoroquinolones in milk samples based on a multi-pumping flow system.

An automated and miniaturized chemiluminescence method for screening of fluoroquinolones in milk samples was proposed. The method was based on magnetic dispersive micro-solid phase extraction of analytes followed by the chemiluminescence determination of the total fluoroquinolones content using a multi-pumping flow system. In the developed method, Zr-Fe-C magnetic nanoparticles were used as an efficient sorbent for separation of fluoroquinolones from sample matrix. The chemiluminescence intensity obtained for Ce4+-SO32--Tb3+ chemiluminescence system was greatly increased in the presence of the analytes. Under the optimal conditions, the detector response for fluoroquinolones was linear in the concentration ranges from 5·10-9 to 1·10-6 mol L-1 with respect to fleroxacin. The limit of detection, calculated from a blank test based on 3σ, was 2·10-9 mol L-1 with respect to fleroxacin. The presented method demonstrated to be a good tool for available and cost-effective point-of-need screening fluoroquinolones in milk samples.

An automated magnetic dispersive micro-solid phase extraction in a fluidized reactor for the determination of fluoroquinolones in baby food samples.

An automated magnetic dispersive micro-solid phase extraction procedure in a fluidized reactor was developed for the determination of fluoroquinolone antimicrobial drugs (fleroxacin, norfloxacin and ofloxacin) in meat-based baby food samples. A stepwise injection system was successfully combined with afluidized reactorand applied for the magnetic dispersive micro-solid phase extraction procedure automation. The developed automated procedure involved injection of the sample solution into the fluidized reactor followed by the on-line separation of the analytes from the sample matrix based on fluidized beds strategy using magnetic nanoparticles, elution and determination of the analytes using a high performance liquid chromatography system with fluorescence detection. The floating of the magnetic nanoparticles in a liquid sample phase was accomplished by air-bubbling. In the developed method Zr-Fe-C magnetic nanoparticles were used as an efficient sorbent for the determination of fleroxacin, norfloxacin and ofloxacin. Under the optimal conditions, the calibration graphs were linear over the concentration ranges of 10-1000 µg L-1 for fleroxacin (R2 = 0.996), 5-1000 µg L-1for norfloxacin (R2 = 0.998) and ofloxacin (R2 = 0.998). The limits of detection, calculated from the blank tests based on 3σ, were 3.0 µg L-1forfleroxacin, 1.5 µg L-1for norfloxacin and ofloxacin. The limits of quantification, calculated from the blank tests based on 10σ, were 10 µg L-1 forfleroxacin, 5 µg L-1for norfloxacin and ofloxacin. The method was applied for the determination of fluoroquinolonesin meat-based baby food samples and the results were compared with those obtained by the reference method. The recovery values for all analytes were within of 86-122% range.

Silicon-containing nanocarriers for targeted drug delivery: synthesis, physicochemical properties and acute toxicity.

Silicon-containing nanoparticles (NPs) are considered promising drug carriers for targeted drug delivery. In this study, we investigated the physical and chemical properties of silicon-containing NPs, including silica and organomodified silica NPs (SiO2NPs and OrSiO2NPs, respectively), with different surface modifications, with the aim of increasing drug-loading efficiency. In addition, we described the original synthesis methods of different sizes of OrSiO2NPs, as well as new hybrid OrSiO2NPs with a silica core (SiO2 + OrSiO2NPs). Animal experiments revealed that the silicon-containing NPs investigated were non-toxic, as evidenced by a lack of hemodynamic response after intravenous administration. Bioelimination studies showed rapid renal excretion of OrSiO2NPs. In drug release kinetics studies, adenosine was immobilized on SiO2NPs using three different approaches: physical adsorption, ionic, and covalent bonding. We observed that the rate of adenosine desorption critically depended on the type of immobilization; therefore, adenosine release kinetics can be adjusted by SiO2NP surface modification technique. Adsorption of adenosine on SiO2 + OrSiO2NPs resulted in a significant attenuation of adenosine-induced hypotension and bradycardia.

Passive targeting of ischemic-reperfused myocardium with adenosine-loaded silica nanoparticles.

Pharmacological agents suggested for infarct size limitation have serious side effects when used at cardioprotective doses which hinders their translation into clinical practice. The solution to the problem might be direct delivery of cardioprotective drugs into ischemic-reperfused myocardium. In this study, we explored the potential of silica nanoparticles for passive delivery of adenosine, a prototype cardioprotective agent, into ischemic-reperfused heart tissue. In addition, the biodegradation of silica nanoparticles was studied both in vitro and in vivo. Immobilization of adenosine on the surface of silica nanoparticles resulted in enhancement of adenosine-mediated infarct size limitation in the rat model. Furthermore, the hypotensive effect of adenosine was attenuated after its adsorption on silica nanoparticles. We conclude that silica nanoparticles are biocompatible materials that might potentially be used as carriers for heart-targeted drug delivery.

Targeted drug delivery into reversibly injured myocardium with silica nanoparticles: surface functionalization, natural biodistribution, and acute toxicity.

The clinical outcome of patients with ischemic heart disease can be significantly improved with the implementation of targeted drug delivery into the ischemic myocardium. In this paper, we present our original findings relevant to the problem of therapeutic heart targeting with use of nanoparticles. Experimental approaches included fabrication of carbon and silica nanoparticles, their characterization and surface modification. The acute hemodynamic effects of nanoparticle formulation as well as nanoparticle biodistribution were studied in male Wistar rats. Carbon and silica nanoparticles are nontoxic materials that can be used as carriers for heart-targeted drug delivery. Concepts of passive and active targeting can be applied to the development of targeted drug delivery to the ischemic myocardial cells. Provided that ischemic heart-targeted drug delivery can be proved to be safe and efficient, the results of this research may contribute to the development of new technologies in the pharmaceutical industry.