Investigating an organ-targeting platform based on hydroxyapatite nanoparticles using a novel in situ method of radioactive 125Iodine labeling

In this study, we have investigated the synthesis of nanoparticles of hydroxyapatite (HAp) and hydroxyapatite coated with chitosan (HAp/Ch) and the chitosan-poly-d,l-lactide-co-glycolide polymer blend (HAp/Ch-PLGA) as an organ-targeting system. We have examined and defined the final destination, as well as the dynamics and the pathways of the synthesized particles following intravenous administration in vivo.\ud \ud The XRD, ZP, FT-IR and SEM analyses have confirmed that the hydroxyapatite nanoparticles with d50 = 72 nm are coated with polymers. Radioactive 125-Iodine (125I), a low energy gamma emitter, was used to develop a novel in situ method for the radiolabeling of particles and investigation of their biodistribution. 125I-labeled particles exhibited high stability in saline and serum over the second day, which justified their use in the following in vivo studies.\ud \ud The biodistribution of 125I-labeled particles after intravenous injection in rats differed significantly: HAp particles mostly targeted the liver, HAp/Ch the spleen and the liver, while HAp/Ch-PLGA targeted the lungs. Twenty-four hours post injection, HAp particles were excreted completely, while both 125I-HAp/Ch and 125I-HAp/Ch-PLGA were retained in the body for a prolonged period of time with more than 20% of radioactivity still found in different organs

Evalaution of radioiodination of synthesised meta-iodobenzylguanidine catalyzed by in situ generated Cu(i)

Meta-iodobenzylguanidine (m-IBG) is a biogenic amine precursor, noradrenaline analogue, which is actively taken up by tumors. In tracer amounts, [123/131I]-m-IBG is used as a radiopharmaceutical to target normal and malignant tissues of neuroadrenergic origin for diagnostic scintigraphy, and labeled with higher activities of 131I, it is used for therapy of phenochromocytoma and neuroblastoma. The increased clinical therapeutic use of unlabeled m-IBG at doses of up to 40 mg/m2 emphasizes the need for syntheses and an established quality protocol for this substance that relies on verifiable analytical parameters. Evaluation of radioiodination was necessary to obtain higher labeling yield (we achieved over 90% instead no more than 70%), because isotopic exchange labeling of m-IBG with 131I catalyzed by Cu(I) is much more efficient than with conveniently used ammonium sulphate.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Insulin responses to acute glucose infusions in Buša and Holstein-Friesian cattle breed during the peripartum period: Comparative study

The aim of this study was to compare insulin responsevness to acute glucose infusion in cows of Holstein Friesian (HF) and Buša breeds during the peripartal period. Eight cows per each group (HF and Buša), were chosen. At day 7 prior to calving (ante partum) and day 14 after calving (post partum) animals were subjected to a glucose tolerance test (GTT). Blood samples were taken immediately before infusion and 15, 30, 60, 120 and 180 min thereafter. Glucose and insulin concentrations were measured in each blood sample, while BHBA and NEFA were measured only in samples taken before the infusion. QUICKY an indicator of insulin resistance in cows was calculated. Basal glycemia did not significantly differ between the breeds. Basal insulinemia was significantly higher in Buša than in HF cows in both examined periods (p<0.001, respectively). Basal NEFA levels tended (p=0.06) to be higher in Buša cows compared with those of HF ante partum, and was significantly higher (p<0.001) post partum. Basal BHBA was significantly lower in Buša than HF cows in both examined periods (p<0.01; p<0.001). QUICKI was significantly lower in Buša compared to HF cows both ante partum and post partum periods (p<0.001, respectively). Glycemia determined during GTT were higher in Buša than HF cows, both ante partum and post partum, but significantly starting from minute 15 ante partum i.e. minute 30 post partum. Insulinemia determined during GTT was significantly lower at min 15, and significantly higher starting from min 90 in Buša than HF cows, both ante partum and post partum. Results obtained in this study indicate on difference in insulin responsevness to acute glucose infusion between the examined breeds, which is probably a consequence of the difference in the degree of negative energy balance rather than of selection on high milk production. Namely, decreased insulin tissues sensitivity and decreased insulin responsiveness in Buša compared to HF cows is probably the consequence of inadequate energy intake from alimentary sources which leads to enhanced usage of energy from body reserves. [Projekat Ministarstva nauke Republike Srbije, br. 46002

The success rate of hydroxyapatite nanoparticles coated with bioresorbable polymers in a biological environment

Hydroxyapatite (HAp) nanoparticles coated with bioresorbable polymers have been successfully used as filler, carriers of antibiotics, vitamins and stem cells in bone tissue engineering. Interactions in the microenvironment of nanoparticulate hydroxyapatites and tissues are of a particular interest and present a challenge in regenerative medicine. The phenomena that influence the success of targeting and controlled operation or therapeutic nanosystems are numerous and complex: size, shape, surface charge, functional groups of nanoparticles, electrical double-layer formation, zeta potential, partial molar free energy, sorption molar free energy, isoelectric point of solid–liquid interface; receptor–ligand binding interactions of nano-bio interface etc. In our studies we present the synthesis, characterization, in vitro and in vivo research of nanoparticulate form of HAp-coated polymers systems. Synthesized nanoparticulate HAp coated with different types of bioresorbable polymers: poly(D,L-lactide-co-glycolide), chitozan and other similar by the solvent/non-solvent method. The physical and chemical analyses have confirmed that HAp particles are coated with bioresorbable polymers. Results of spectroscopic analysis suggests formation of hydrogen bonds between the surface groups of HAp and =O and –H groups in the polymer chain from bioresorbable polymers. By adding nanoparticulate HAp in the polymer matrix was achieved the changes in the partial molar free energy and sorption molar free energy of the system. In vitro results showed satisfactory biocompatibility of nanoparticulate HAp-coated polymers systems. The use of these systems in the form of filler was achieved a high quality osteogenesis in reconstruction of bone tissue, in vivo.The biodistribution of 125I-labeled HAp particles after intravenous injection in rats showed the potential use of these materials as a organ-targeting system: uncoated-HAp mostly targeted the liver, coated-HAp spleen and lungs

Multicore flower-like magnetite for potential application in cancer nanomedicine

Nanomaterials are intensively researched both from the fundamental aspect due to new properties at the nanoscale, as well as the aspect of their application in many areas of technology. Magnetic nanoparticles (MNPs) are being tested for use in the diagnosis and therapy of diseases. A new field of medicine, Magnetic nanomedicine is primarily based on the application of MNPs as drug carriers, diagnostic agents in Magnetic Resonance Imaging (MRI) and heat generators in magnetic hyperthermia. Among nanoparticles, magnetic nanoplatforms based on iron oxides for cancer diagnosis and therapy (Cancer nanomedicine) are the most researched and clinically tested. This study presents the results of research into the physicochemical properties of iron oxide nanoparticles prepared by the polyol route, as well as their testing for potential applications as agents in magnetic hyperthermia (MH) and radionuclide carriers (vectors) for the diagnosis and therapy of malignant diseases. Multicore iron oxide structures synthesized by the "polyol" method represent clusters of single-core nanoparticles or crystallites. The dimensions of the single core particles are \textasciitilde13.5 nm, while the nanoflowers formed by clustering are \textasciitilde25 nm, depending on the applied synthesis parameters. For targeted medical applications, nanoflowers are coated with different ligands in order to increase colloidal stability and biocompatibility. The best results were by coating MNPs with polyacrylic acid (PAA). The multifunctionality of nanoflowers was investigated by measuring their hyperthermic efficiency for applications in magnetic hyperthermia and radiolabeling with diagnostic (99mTc) and therapeutic radionuclides (177Lu, 90Y). In addition to traditional methods of cancer therapy (surgery, radiotherapy, and chemotherapy), new ways of therapy such as MH are constantly being developed. MH is a therapy based on the property of MNPs that when placed in an alternating (AC) magnetic field, transform the electromagnetic energy of the field into heat. When located inside a tumor, MNPs can locally generate a temperature of 42-46 °C and destroy cancer cells by heat. The hyperthermic efficiency of MNPs is expressed through the Intrinsic Loss Power (ILP) parameter. The measured ILP was 7.3 nHm2/kg which is considered one of the higher reported values found in the literature for iron oxides. Nanoflowers were radiolabeled with 99mTc, 177Lu, and 90Y radionuclides. The in vitro stability of radiolabeling was investigated. Good in vitro stability indicates that the formed radioactive particles can be used simultaneously for bi-modal cancer therapy (MH and radionuclide therapy) or for MH therapy and diagnostics (theranostics), in the case of labeling with 99mTc

Tailoring IONP shape and designing nanocomposite IONS@GN toward modification of SPCE to enhance electrochemical degradation of organic dye

Iron oxide nanoparticles (IONP) with different distinctive morphologies (spherical, cubic, flower-like and needles) were utilized for modification of screen-printed carbon electrodes (SPCE) to be used for synthetic organic dye degradation by an electrochemical approach. This platform was implemented for removal of the synthetic organic dye, Reactive Black 5 (RB5) in aqueous solution. Modified SPCE with spherically shaped IONP (IONS) had the highest dye removal efficiency. Thus, IONS were then used for surface decoration of the most common carbon-based materials (graphene, graphene oxide, carboxylated graphene, graphene nanoribbons, graphene nanoplatelets, single- and multi-wall carbon nanotubes), and the nanocomposites formed were deposited on the electrode surfaces. Using IONS/graphene composite (IONS@GN) for electrode modification resulted in the best effect. Removal of RB5 with this electrode was 51% better in comparison with bare SPCE, reducing the time required for complete dye degradation from 61 to 30 min Using IONS-modified SPCE, total RB5 removal occurred in 51 min, improving the performance by 16% over that of bare SPCE. The effects determined, i.e., the best IONP morphology and best type of carbon-based material for nanocomposite formation to enhance RB5 removal will provide guidelines for further modifications of SPCE with nanomaterials and nanocomposites, for application of this electrochemical approach in the degradation of organic pollutants

Synthesis, Surface Modification and Magnetic Properties Analysis of Heat-Generating Cobalt-Substituted Magnetite Nanoparticles

Here, we present the results of the synthesis, surface modification, and properties analysis of magnetite-based nanoparticles, specifically Co0.047Fe2.953O4 (S1) and Co0.086Fe2.914O4 (S2). These nanoparticles were synthesized using the co-precipitation method at 80 ◦C for 2 h. They exhibit a single-phase nature and crystallize in a spinel-type structure (space group Fd3m). Transmission electron microscopy analysis reveals that the particles are quasi-spherical in shape and approximately 11 nm in size. An observed increase in saturation magnetization, coercivity, remanence, and blocking temperature in S2 compared to S1 can be attributed to an increase in magnetocrystalline anisotropy due to the incorporation of Co ions in the crystal lattice of the parent compound (Fe3O4). The heating efficiency of the samples was determined by fitting the Box-Lucas equation to the acquired temperature curves. The calculated Specific Loss Power (SLP) values were 46 W/g and 23 W/g (under HAC = 200 Oe and f = 252 kHz) for S1 and S2, respectively. Additionally, sample S1 was coated with citric acid (Co0.047Fe2.953O4@CA) and poly(acrylic acid) (Co0.047Fe2.953O4@PAA) to obtain stable colloids for further tests for magnetic hyperthermia applications in cancer therapy. Fits of the Box-Lucas equation provided SLP values of 21 W/g and 34 W/g for CA- and PAA-coated samples, respectively. On the other hand, X-ray photoelectron spectroscopy analysis points to the catalytically active centers Fe2+/Fe3+ and Co2+/Co3+ on the particle surface, suggesting possible applications of the samples as heterogeneous self-heating catalysts in advanced oxidation processes under an AC magnetic field

Supplemental Selenium Reduces the Levels of Biomarkers of Oxidative and General Stress in Peripartum Dairy Cows

The aim of this investigation was to determine the influence of oxidative stress upon general stress in dairy cows on parturition and whether the indicators of stress can be reduced by selenium (Se) supplementation. A total of 36 animals were divided into 3 groups 21 days prepartum and treated with a single-term intra muscular supplement of sodium selenite: Control group - 0 mg; group Se10 - 10 mg; group Se20 - 20 mg. Se supplementation significantly raised blood Se content and glutathione peroxidase (GPx) activity in groups Se10 and Se20, compared to Control, although there was no marked difference between supplemented groups. Plasma malondialdehyde (MDA) and cortisol concentrations were significantly reduced in supplemented groups Se10 and Se20, compared to Control. A negative correlation was detected between blood GPx activity and plasma MDA, while a positive correlation was determined between plasma MDA and cortisol concentrations. These results indicate that prepartum Se supplementation can be utilized for a partial relief of stress in cows during labor by augmenting the antioxidative action of GPx

Blokada sinteze azot-monoksida stimuliše aktivnost korteksa nadbubrežne žlezde

Objective. Although it is known that nitric oxide modulates the activity of hypothalamic-pituitary-adrenal axis, its functional significance has not been elucidated. Additionally, there is no information on the effect of nitric oxide on cortical expression of glucocorticoid receptor. The purpose of this study was to investigate the influence of endogenous nitric oxide on structure and function of rat adrenal cortex and adrenocortical expression of glucocorticoid receptor. Methods. Adult female Wistar rats showing diestrus day 1 were treated with Nω-nitro-L-arginine-methyl ester (LNAME), an inhibitor of all three isoforms of nitric oxide synthase, at a dose of 30 mg/kg, subcutaneously. The concentrations of adrenocorticotropic hormone (ACTH) and corticosterone were determined by radioimmunoassay. Stereological and immunohistochemical analyses were performed on paraffin sections. Results. Blockade of nitric oxide production significantly increased blood levels of ACTH and corticosterone. Stereological analysis showed that treatment with L-NAME significantly decreased numerical density of the cells in all cortical zones. Consistent with the decreased numerical density, L-NAME significantly increased the volume of cells in cortical zones. Inhibition of nitric oxide synthesis decreased expression of glucocorticoid receptor in zona fasciculata and zona reticularis. Conclusion. Obtained results indicate that endogenous nitric oxide inhibits activity of adrenal cortex and modulates expression of glucocorticoid receptor.Cilj. Iako je poznato da azot-monoksid moduliše aktivnost hipotalamo-hipofizno-nadbubrežne osovine, funkcionalni značaj tog delovanja nije rasvetljen. Pored toga, dejstvo azot-monoksida na kortikalnu ekspresiju glukokortikoidnog receptora nije istraženo. Cilj ovog rada bio je da se ispita uticaj endogenog azot-monoksida na strukturu i funkciju kore nadbubrežne žlezde pacova i adrenokortikalnu ekspresiju glukokortikoidnog receptora. Metode. Odrasle ženke pacova Wistar soja u metestrusnoj fazi ciklusa tretirane su Nω-nitro-L-arginin metil esterom (L-NAME), inhibitorom sve tri izoforme azotmonoksid sintaze, u dozi 30 mg/kg, subkutano. Koncentracije adrenokortikotropnog hormona (ACTH) i kortikosterona u krvi određene su radioimunološkom metodom. Na parafinskim presecima nadbubrežne žlezde izvršena je stereološka i imunohistohemijska analiza korteksa. Rezultati. Blokada sinteze azot-monoksida značajno povećava koncentracije ACTH i kortikosterona u krvi. Stereološka analiza je pokazala da tretman sa L-NAME značajno smanjuje numeričku gustinu ćelija u svim kortikalnim zonama. U skladu sa smanjenom numeričkom gustinom, L-NAME značajno povećava volumen ćelija u sve tri zone korteksa. Inhibicija sinteze azot-monoksida smanjuje ekspresiju glukokortikoidnog receptora u zoni fascikulati i zoni retikularis. Zaključak. Dobijeni rezultati ukazuju na mogućnost da endogeni azot-monoksid inhibiše aktivnost kore nadbubrežne žlezde i da moduliše ekspresiju glukokortikoidnog receptora

Radiolabeled surface-modified single-core (Mg,Fe)3O4 colloidal nanoparticles as vectors in radionuclidetherapy of cancer

A series of MgxFe3-xO4 (x=0, 0.1, 0.2, 0.4, 0.6, 0.8, and 1) magnetic nanoparticles (MNP) were synthesized by a two-step procedure, a co-precipitation method followed by hydrothermal treatment in a microwave field. The MNP are single-core, with crystallite size gradually decreasing from 15.5(3) up to 2.5(3) nm with an increase ofx. TEM images show pseudospherical log-normally distributed particles with an average particle diameter of 19.8 nm and a polydispersity index of 26.1% for magnetite. The particle diameter decreases with the increase of magnesium (x) in the formula unit. The colloidal stability of MNP was achieved by their surface modification with citric acid (CA), oleic acid (OA) and polyethylene glycol (PEG). The cytotoxic activity of uncoated and coated Mg0.6Fe2.4O4 was tested against target malignant cells (HeLa, LC174, A549) and normal MRC5 cells. The investigated MNP show moderate cytotoxic activity against the tested malignant cells in vitro. In contrast, MNP didn’tshow any significant cytotoxic effect against normal cells. HeLa cells exhibited the highest susceptibility among the malignant cells. Mg0.6Fe2.4O4@OA show good cytotoxic activity against all examined malignant cells, significantly higher than other tested MNP. It can be seen that Mg0.6Fe2.4O4@PEG show a lower cytotoxic activity compared to all analyzed MNP. A direct method was used for labeling with radionuclide 90Y, which involves incubation of MNP with 90Y at a certain temperature and time. The labeling yield of the 90Y-coated MNP was determined by analyzing the radiochemical purity after labeling. 90YMg0.2Fe2.8O4@PEG were labeled in high yield (100%), while the yield for 90YMg0.2Fe2.8O4@CA was 83%. In vitro stability of 90Y-coated MNP at room temperature in physiological solution and human serum was monitored within 72 h from the moment of labeling by determining the radiochemical purity of ITLC-SG by radio chromatographic method. The stability of 90Y-Mg0.2Fe2.8O4@PEG was about 97%, while 90Y-Mg0.2Fe2.8O4@CA stability was 73%. The results of this study indicate that radiolabeled surface-modified (Mg, Fe)3O4 can be used as vectors in radionuclide therapy of malignant diseases