János Borbély

99mTc-labelled nanosystem as tumour imaging agent for SPECT and SPECT/CT modalities

We report the synthesis, in vitro and in vivo investigation of folate-targeted, biocompatible, biodegradable self-assembled nanoparticles radiolabelled with (99m)Tc, as potential new SPECT or SPECT/CT imaging agent. Nanoparticles with hydrodynamic size in the range of 75-200 nm were prepared by self-assembly of chitosan and folated poly-γ-glutamic acid, and then radiolabelled with (99m)Tc. The nanoparticles target tumour cells overexpressing folate receptors and internalize specifically into them to realize early tumour diagnosis detected by SPECT and SPECT/CT modalities. Rat hepatocellular carcinoma cells were used as model system. Cell specificity and tumour targeting efficacy of these nanosystems were investigated in vitro, and in vivo using SPECT and fusion nanoSPECT/CT imaging. In vitro results showed that the radiolabeled nanosystem was efficiently internalized by tumour cells. Whole-body biodistribution of the new radiolabelled, folate-targeted nanoparticles revealed higher uptake in the tumorous kidney compared to the non-tumorous contralateral side. Uptake by the lungs and thyroids was negligible, which confirmed the stability of the nanoparticles in vivo. In vivo SPECT and SPECT/CT imaging visually reinforced the uptake results and were in accordance with the biodistribution data: the new nanoparticles as a targeted contrast agent improve tumour targeting and are able to detect folate-receptor-overexpressing tumours in animal models with enhanced contrast.

Nanoparticles from Chitosan

Novel biodegradable nanoparticles were synthesized by chemical modification of the chitosan linear chain. A natural dicarboxylic acid (malic acid) was used as a crosslinking agent for intramolecular covalent condensation reaction to obtain hydrophilic nanoparticles based on chitosan. A variety of methods including, solubility studies, laser light scattering (DLS), transmission electron microscopy (TEM) and nuclear magnetic resonance (NMR) was used to characterize the crosslinked macromolecules. The prepared biodegradable chitosan nanoparticles, soluble in aqueous media, might be useful for various biomedical applications, like injectable drug- or gene-delivery systems.

Preparation and chemical modification of poly-γ-L-glutamic acid

Poly-γ-l-glutamic acid was synthesized in optimized fermentor cultivation ofBacillus licheniformis. The polypeptide obtained was esterified using benzyl- and butylbromides. Benzyl esters with 30, 60 and 100% degree of esterification were prepared. Solubility of the products in dimethyl sulfoxide, chloroform, methanol and in water was significantly different from these ones of original polymer.

Folate receptor targeted self-assembled chitosan-based nanoparticles for SPECT/CT imaging: Demonstrating a preclinical proof of concept

A new biocompatible, biodegradable, self-assembled chitosan-based nanoparticulate product was successfully synthesized and radiolabeled with technetium-99m, and studied as a potential new SPECT or SPECT/CT imaging agent for diagnosis of folate receptor overexpressing tumors. In the present study we examined the conditions of a preclinical application of this labeled nanosystem in early diagnosis of spontaneously diseased veterinary patient using a human SPECT/CT device. The results confirmed that the nanoparticles accumulated in tumor cells overexpressing folate receptors, contrast agent revealed higher uptake in the tumor for a long time. Preclinical trials verified that the new nanoparticles are able to detect folate-receptor-overexpressing tumors in spontaneously diseased animal models with enhanced contrast.

Investigation of 1,3,5-tris(2-metoxypropane)benzene/BCl3 initiated living isobutylene polymerization by C13 and B11 NMR spectroscopy

SummaryThe living carbocationic polymerization of isobutylene initiated by 1,3,5-tris(2-methoxypropane) benzene (TriCumOMe)/BCl3 system was investigated by C13 and B11 NMR spectroscopy. The reaction between the TriCumOMe and BCl3 at-30°C in CH2Cl2 after 15 mins reaction time resulted in 1,3,5-tris(2-chloropropane) benzene (TriCumCl) and methyl-dichloroboronite (BCl2OMe). The same system in the presence of isobutylene yielded three-arm star, chlorine terminated telechelic polyisobutylene and BCl2OMe. No counterions, i.e., BCl3OMe⊝, BCl4⊝, or neutral boron complexes, e.g., TriCumOMe, 3BCl3 could be detected. The simultaneous measurement of static permittivity (direct monitoring method) showed different reaction rate patterns in the case of AMI method, and when the TriCumOMe+BCl3 mixture was aged and the polymerization was started by isobutylene.

The reactions of chromone and 2-hydroxychromanone with hydroxylamine

Abstract Chromone and 2-hydroxychromanone react with hydroxylamine to give several products through attack at Ca2. The aldoxime 2 is transformed to dioxime 4 or to isoxazole 3 . The dioxime exists as a tautomer mixture; it reacts in several ways, giving chromoneoxime 8 , isoxazole 10 and a new isoxazoline 9 .

Cancer cell targeting and imaging with biopolymer-based nanodevices

We report here the synthesis, in vitro and in vivo investigation of magnetic resonance imaging (MRI) active nanoparticles, which target folate receptor overexpressing tumor cells. Self-assembled nanoparticles with a hydrodynamic size of 50-200 nm were prepared from poly-γ-glutamic acid and chitosan biopolymers with Gd-ions. The nanoparticles are biocompatible, non-toxic and stable for several months in aqueous media. In vitro assays using confocal microscopy, flow cytometry and MR imaging on HeLa human cervix carcinoma tumor cells showed that folic acid targeted nanoparticles were internalized specifically in a folate receptor dependent manner. In vivo study confirmed, that, considerable accumulation of nanosystems was found compared with the control animal represented by the MR images. Relaxometry measurements demonstrated that the nanoparticle-Gd complexes drastically change the signal intensity of the tumor cells. Because of the contrast enhancement, they are attractive candidates as potential contrast agents for a variety of diagnostic applications including early diagnosis of tumors.

Stereochemical studies of 2-hydroxychromanones by 1H NMR spectroscopy

Abstract 2-Hydroxychromanones ( 2a – 2f ) were synthesized by ring closing of 2-hydroxyacetophenones ( 1a , b ) and 2-hyroxypropiophenones ( 1c – 1f ). In the case of 2-hydroxy-3-methyl-chromanones ( 2c – 2f ) a mixture of cis and trans isomers was obtained. The trans isomers are conformalionally homogeneous, the cis isomers exist in a conformational equilibrium. At room temperature the isomers are transformed into each other via opening of the heteroring. This process becomes faster in alkaline medium and the β-diketo form 4 can also be observed.

Synthesis and characterization of poly-(methyl methacrylate-co-N-4-bromophenyl maleimide)

Radical copolymerization of methyl methacrylate (MMA, M1) and N-(4-bromophenyl) maleimide (N4BrPhMI, M2) in dioxane at 60 °C was performed with AIBN as initiator. Analysis of composition data points was carried out to a terminal model copolymerization. Using 1H, 13C and DEPT NMR measurements, the observed resonances were assigned. Glass transition temperatures were determined by DSC and a linear correlation was found between the Tg values and M2 content of the copolymers.

Reactive propylene oligomers - II. Propylene oligomers with primary-OH, tertiary-OH and α, β-di-OH end groups

SummaryPropylene oligomers with primary-OH, tertiary-0H andα,β-di-OH end groups have been prepared by converting the isopropenyl-ended oligomers with hydroboration-oxydation, oxymercuration-demercuration and performic acid hydroxylation reactions, respectively.