Influence of ligand structure on anticancer and antioxidant properties of rhenium cluster compounds

Досліджено протипухлинну активність системи реній-платину, що містить цис-дикарбоксилати ренію (ІІІ) із різними алкільними лігандами, кількість еритроцитів крові, їх морфологічний склад, еритроцитарну стійкість, концентрацію гемоглобіну крові, активність каталази, вміст ТБК-активних продуктів у плазмі крові щурів при розвитку карциноми Герена Т8 щурів. Показано, що система реній-платину має значний антиоксидантний ефект і пригнічує ріст пухлини, що є максимальним для сполуки з півалатним лігандомИсследованы противоопухолевая активность системы рений-платина, которая содержит цис-дикарбоксилаты рения (III) с разными алкильными лигандами, количество эритроцитов крови, их морфологический состав, эритроцитарная стойкость, концентрация гемоглобина в крови, активность каталазы, концентрация ТБК-активных продуктов плазмы крови крыс при развитии карциномы Герена Т8 крыс. Показано, что система рений-платина имеет значительный антиоксидантный эффект и угнетает рост опухоли, что является максимальным для соединения с пивалатным лигандом.Under the model growth of T8 Guerin’s carcinoma in rats we studied the anticancer activity of the system rhenium-platinum, which includes cis-dicarboxylates of rhenium (III) with different alkyl ligands, erythrocytes number and its morphological structure, erythrocytic stability, blood haemoglobin concentration, catalase activity and concentration of TBA-active products in the rats blood plasma. The renium-platinum system had considerable antioxidat effect and prevented the growth of tumour, that was maximal for a compound with the pivalate ligand

Correction to "Luminescent Gold Nanocluster-Decorated Polymeric Hybrid Particles with Assembly-Induced Emission"

Correction to “Luminescent Gold Nanocluster-Decorated Polymeric Hybrid Particles with Assembly-Induced Emission

Liposomal formulations of mistletoe produced by centrifugal technologies and cell proliferation analysis of both mistletoe extracts and isolated mistletoe lectin I = Liposomale Formulierung von Mistelextrakten durch Zentrifugationsverfahren und Analyse der Zellproliferation von Gesamtextrakten und isoliertem Mistellektin I

Um Liposomen aus Nanoemulsionen herzustellen, wird ein Zentrifugationsverfahren entwickelt, das eine hohe Einkapselungseffizienz und asymmetrische Membranen ermöglicht. Heparin-Komplexe werden für die Bildung einer stabilen Schutzschicht verwendet. Um die Erprobung der liposomalen Formulierungen in vitro und in vivo zu ermöglichen, wurden Mistelpräparate mit unterschiedlicher Viscotoxin-(VT) und Mistellektin-(ML) Zusammensetzung sowie isoliertes ML°I an Maus-Zelllinien erprobt. Ein Proliferationstest wurde durchgeführt, um die inhibierenden Konzentrationen (IC50) zu ermitteln und sensitive Zelllinien für in vivo Experimente auszuwählen. abnobaVISCUM (AV) Pini Präparate, die den geringsten Gesamtgehalt an ML und eine Dominanz von ML III aufweisen, zeigten bei B16-F10 Melanomzellen eine stärkere Inhibierung der Proliferation im Vergleich zu den ML I reichen Präparaten AV Fraxini und Quercus. Für AV Fraxnini und AV Quercus wurde gezeigt, dass die Zytotoxizität überwiegend auf ML I zurückzuführen ist und ML I daher als potentieller Wirkstoff zur Verkapselung in Liposomen geeignet ist. Auf isoliertes ML I reagiert die getestete Kolonkarzinomzelllinie C26 deutlich empfindlicher als die aggressive B16-F10 Melanomzelllinie. Diese Ergebnisse erlauben den Vergleich eines sensitiven mit einem aggressiven Tumormodell in vivo. Im Vergleich zu C26 ist die Makrophagenzelllinie RAW264.7 relativ unempfindlich gegenüber isoliertem ML I. Die Ergebnisse deuten auf die Möglichkeit einer gezielten Therapie von z.B. Kolontumoren hin, bei der die Immunfunktionen intakt bleiben

Biotin-decorated all-HPMA polymeric micelles for paclitaxel delivery

To avoid poly(ethylene glycol)-related issues of nanomedicines such as accelerated blood clearance, fully N-2-hydroxypropyl methacrylamide (HPMAm)-based polymeric micelles decorated with biotin for drug delivery were designed. To this end, a biotin-functionalized chain transfer agent (CTA), 4-cyano-4-[(dodecylsulfanylthiocarbonyl)-sulfanyl]pentanoic acid (biotin-CDTPA), was synthesized for reversible addition-fragmentation chain-transfer (RAFT) polymerization. Amphiphilic poly(N-2-hydroxypropyl methacrylamide)-block-poly(N-2-benzoyloxypropyl methacrylamide) (p(HPMAm)-b-p(HPMAm-Bz)) with molecular weights ranging from 8 to 24 kDa were synthesized using CDTPA or biotin-CDTPA as CTA and 2,2'-azobis(2-methylpropionitrile) as initiator. The copolymers self-assembled in aqueous media into micelles with sizes of 40-90 nm which positively correlated to the chain length of the hydrophobic block in the polymers, whereas the critical micelle concentrations decreased with increasing hydrophobic block length. The polymer with a molecular weight of 22.1 kDa was used to prepare paclitaxel-loaded micelles which had sizes between 61 and 70 nm, and a maximum loading capacity of around 10 wt%. A549 lung cancer cells overexpressing the biotin receptor, internalized the biotin-decorated micelles more efficiently than non-targeted micelles, while very low internalization of both types of micelles by HEK293 human embryonic kidney cells lacking the biotin receptor was observed. As a consequence, the paclitaxel-loaded micelles with biotin decoration exhibited stronger cytotoxicity in A549 cells than non-targeted micelles. Overall, a synthetic pathway to obtain actively targeted poly(ethylene glycol)-free micelles fully based on a poly(HPMAm) backbone was established. These polymeric micelles are promising systems for the delivery of hydrophobic anticancer drugs

Delivery of riboflavin-5’-monophosphate into the cornea: can liposomes provide any enhancement effects?

Keratoconus is a progressive condition caused by the thinning of the cornea, which eventually deforms the front surface of the eye into a cone shape leading to ghosting, multiple images, glare and several other vision problems. Currently keratoconus is treated with UV-induced ribofiavin-mediated collagen cross-linking, which requires a physical removal of the corneal epithelium under topical anesthesia. This study reports the penetration of riboflavin (Rb) and its more water-soluble form, riboflavin-5’- monophosphate (RbP), into the bovine cornea ex vivo. Using ex vivo bovine corneal tissues and 0.8 mg/mL drug solutions in phosphate buffer, it was established that RbP penetration into the cornea within 3 hours of diffusion experiment was greater (17.3 ± 0.8 μg) compared to Rb (10.4 ± 4.2 μg). In the cornea RbP was found to convert to Rb, which is mediated with enzymes present in this tissue. Several formulations including the conventional and propylene glycol-containing liposomes with encapsulated RbP have been developed and their effect on the drug penetration into the bovine cornea was evaluated. Encapsulation of RbP into the liposomes did not provide any statistically significant improvement in the penetration of RbP into the cornea

POTENTIAL OF BUSINESS ENTITIES: ESSENCE, ASSESSMENT AND ROLE IN NATIONAL DEVELOPMENT

The behavior of macroeconomic indicators (reflecting the development of both the national economy as a whole and that of individual economic sectors) testifies to the low current efficiency of the functioning of economic entities in the context of economic activities. This in turn necessitates scientific substantiation of developing and introducing theoretical and methodological recommendations to ensure innovative development of the country. One of the most effective ways to practically implement this task is to substantiate methods for quantitative assessment of potential in the context of economic activities. The practical value of applying these methods is that the results of the integrated assessment of potential can be used as a criterion for the priority development of certain economic sectors or economic activities

Dérivés amphiphiles de la riboflavine pour le développement de nanosystèmes à ciblage tumoral

Riboflavin (RF) is an essential vitamin for cell growth and development. It possesses interesting physicochemical properties and is internalized by the cells through specific transporters. The first aim of this study was to prepare amphiphile derivatives of RF (RFA) and study their auto-assembly. The second aim was to insert RFA into established drug delivery systems and test their tumour-targeting potential in vitro and in vivo. RFA were prepared by the molecule functionalization with lipid moieties in different positions. One of them, a phospholipid-like derivative (RfdiC14) was able to self-assembly in aqueous solutions into μm-sized 3D objects constituted from slightly curved multilayer lamellas. The bilayer architecture and dynamics were very different from ordinary phospholipids. In contrast, the insertion of small amount of RfdiC14 in a liposome did not influence membrane dynamics and physicochemical characteristics. RfdiC14-functionalised liposomes displayed high and specific uptake in vitro in A431, PC3 cells and HUVECs. The efficiency of RF targeting was also tested in vivo. For that purpose, liposome composition was optimized and a new RF amphiphile with a PEG spacer between RF and lipid was prepared. The tumour accumulation of the liposomes labelled with ICG was studied by photoacoustic imaging in A431 tumour model. The biodistribution of DiR labelled liposomes was accessed by combined μCT/FMT imaging in PC3 tumour model. The results show slight improvement of the tumour accumulation in A431 xenographts and the enhancement of vascular targeting in PC3 tumour model. The overall biodistribution of the RF-targeted liposomes was comparable to control.La riboflavine (RF) est une vitamine essentielle pour la croissance et le développement cellulaire. Elle possède des propriétés physico-chimiques intéressantes et est internalisée dans les cellules par des transporteurs spécifiques. Le premier objectif de ce projet était de synthétiser des dérivés amphiphiles de la RF (RFA) et d'étudier leurs capacités d'auto-assemblages. Le second objectif était d'insérer les RFA dans des liposomes et d'évaluer leur efficacité de ciblage tumoral in vitro et in vivo. La préparation des différents RFA repose sur l'ajout d'un lipide en différentes positions de la RF. L’un d'eux, de type phospholipide (RfdiC14) a été capable de former des objets tridimensionnels de taille μm constitués de lamelles multicouches dont l’architecture et la dynamique sont très différentes de celles des phospholipides classiques. L’insertion de RfdiC14 dans des liposomes est efficace et n’influence pas leurs propriétés physico-chimiques. Les liposomes fonctionnalisés ont montré une internalisation cellulaire spécifique dans les lignées A431, PC3 et HUVECs. Afin de tester l’efficacité du ciblage tumoral in vivo, un analogue de RfdiC14 portant un espaceur PEG a été préparé puis inséré dans des liposomes péguylés. Grâce à un marquage adéquat (ICG et DiR), leur accumulation tumorale a été suivie par imagerie photoacoustique dans un modèle A431 et leur biodistribution évaluée par imagerie μCT/FMT dans un modèle PC3. Les résultats montrent une légère amélioration de l’accumulation tumorale dans les xénogreffes A431 et une augmentation du ciblage vasculaire dans le modèle tumoral PC3. La biodistribution globale des liposomes marqués est comparable à celle des contrôles

Riboflavin-based amphiphiles for tumour-targeted nanosystems

La riboflavine (RF) est une vitamine essentielle pour la croissance et le développement cellulaire. Elle possède des propriétés physico-chimiques intéressantes et est internalisée dans les cellules par des transporteurs spécifiques. Le premier objectif de ce projet était de synthétiser des dérivés amphiphiles de la RF (RFA) et d'étudier leurs capacités d'auto-assemblages. Le second objectif était d'insérer les RFA dans des liposomes et d'évaluer leur efficacité de ciblage tumoral in vitro et in vivo. La préparation des différents RFA repose sur l'ajout d'un lipide en différentes positions de la RF. L’un d'eux, de type phospholipide (RfdiC14) a été capable de former des objets tridimensionnels de taille μm constitués de lamelles multicouches dont l’architecture et la dynamique sont très différentes de celles des phospholipides classiques. L’insertion de RfdiC14 dans des liposomes est efficace et n’influence pas leurs propriétés physico-chimiques. Les liposomes fonctionnalisés ont montré une internalisation cellulaire spécifique dans les lignées A431, PC3 et HUVECs. Afin de tester l’efficacité du ciblage tumoral in vivo, un analogue de RfdiC14 portant un espaceur PEG a été préparé puis inséré dans des liposomes péguylés. Grâce à un marquage adéquat (ICG et DiR), leur accumulation tumorale a été suivie par imagerie photoacoustique dans un modèle A431 et leur biodistribution évaluée par imagerie μCT/FMT dans un modèle PC3. Les résultats montrent une légère amélioration de l’accumulation tumorale dans les xénogreffes A431 et une augmentation du ciblage vasculaire dans le modèle tumoral PC3. La biodistribution globale des liposomes marqués est comparable à celle des contrôles.Riboflavin (RF) is an essential vitamin for cell growth and development. It possesses interesting physicochemical properties and is internalized by the cells through specific transporters. The first aim of this study was to prepare amphiphile derivatives of RF (RFA) and study their auto-assembly. The second aim was to insert RFA into established drug delivery systems and test their tumour-targeting potential in vitro and in vivo. RFA were prepared by the molecule functionalization with lipid moieties in different positions. One of them, a phospholipid-like derivative (RfdiC14) was able to self-assembly in aqueous solutions into μm-sized 3D objects constituted from slightly curved multilayer lamellas. The bilayer architecture and dynamics were very different from ordinary phospholipids. In contrast, the insertion of small amount of RfdiC14 in a liposome did not influence membrane dynamics and physicochemical characteristics. RfdiC14-functionalised liposomes displayed high and specific uptake in vitro in A431, PC3 cells and HUVECs. The efficiency of RF targeting was also tested in vivo. For that purpose, liposome composition was optimized and a new RF amphiphile with a PEG spacer between RF and lipid was prepared. The tumour accumulation of the liposomes labelled with ICG was studied by photoacoustic imaging in A431 tumour model. The biodistribution of DiR labelled liposomes was accessed by combined μCT/FMT imaging in PC3 tumour model. The results show slight improvement of the tumour accumulation in A431 xenographts and the enhancement of vascular targeting in PC3 tumour model. The overall biodistribution of the RF-targeted liposomes was comparable to control