Ruthenium(III) complexes entrapped in liposomes with enhanced cytotoxic and anti-metastatic properties

Metal-based anticancer drugs are pivotal in the fight against cancer pathologies. Since 1978 cis-platin was licensed for medical treatment of a wide number of tumor pathologies(1). However its chemiotherapic use is strongly limited by many and severe side effects and acquired tumor resistance. Since these limitations could be overcome by other metal complexes, in the last thirty years ruthenium compounds have been tested showing a remarkable antitumoral and antimetastatic activity associated with a lower toxicity. A hexacoordinate Ru(III) complex (NAMI-A) is currently undergoing advanced clinical evaluation (2). All data indicate that NAMI-A acts as a pro-drug, but the integrity of ruthenium complexes is essential to store the cytotoxic activity. In this scenario the condition of administration of ruthenium drugs are crucial to exploit their anticancer activity (3). In the last years innovative strategies have been produced to vehicle ruthenium ions in tumor cells like aggregates. This study aims to incorporate the ruthenium complexes in the inner aqueous compartment of liposomes and to test biological properties of two NAMI-A like pyridine derivatives. Specifically, we have investigated the pyridine derivatives of the sodium-compensated analogue of NAMI-A, Na[trans-RuCl4(pyridine)(DMSO)] (NAMI-Pyr) and Na[trans-RuCl4(Pytri)(DMSO)] (NAMI-Pytri). In thelatter complex the pyridine ligand is functionalized with a sugar moiety so as to increase biocompatibility and the ability to cross the cell membrane. The stability of the complexes was studied and compared in solution at different pH following UV-VIS spectra. Lipid formulations based on Egg PC were prepared adding Cholesterol, DSPE-PEG2000 joining molar ratio 57/38 /5% w/w respectively in MeOH/CHCl3 (50/50 v/v) mixture and hydrated with 0.9% w/w of NaCl. This composition was selected to reproduce analog supramolecular aggregates in clinical use to vehicle doxorubicin (Doxil). Ruthenium complexes were loaded into liposomes using the passive equilibration loading method. Full drug containing liposomes were structurally characterized by dynamic light scattering (DLS) measurements. Data indicate the formation of stable aggregates with size and shape in the right range for in vivo applications. The amount of encapsulated ruthenium complexes was quantified by means of ICP-AES. Stability and drug release properties of ruthenium containing liposomes were confirmed in buffer. The growth inhibitory effects of both liposomal and free complexes drug were tested on prostate cancer cells (PC3). Preliminary results show high cytotoxic effect of ruthenium complexes delivered by supramolecular aggregates with respect to free complexes drug

Sugar-Incorporated N-Heterocyclic-Carbene-Containing Gold(I) Complexes: Synthesis, Characterization, and Cytotoxic Evaluation

A series of neutral and cationic gold(I) complexes bearing a glucopyranoside-incorporated N-heterocyclic carbene (NHC) ligand are synthetized and structurally characterized. Different secondary ligands (chlorido, phosphane, or sugar–NHC) are employed to tune the properties of the complexes. The antiproliferative effects of the compounds are evaluated against PC-3 prostate cancer cells and a panel of human tumor cell lines. The activities of the phosphane complexes are comparable to that observed for cisplatin. The combined results provide further insights into the biological behavior of NHC–gold complexes

The Impact of Long-Term Exposure to Space Environment on Adult Mammalian Organisms: A Study on Mouse Thyroid and Testis

Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis

POSTO MEDICO AVANZATO (pma) ESPERIENZA DURANTE IL TERREMOTO IN ABRUZZO

GESTIONE DELLA EMERGENZA SANITARIA DEL TERREMOTO IN ABRUZZOMANAGEMENT OF EMERGENCY SITUATION DURING EARTHQUAKE IN ITALY ABRUZZO 200

DYSKINETIC SYNDROME IN A PATIENT WITH FAMILY HISTORY OF SMA

MUSCLE ATROPHY, MIOPATH

TEACHING OF INTERNAL MEDICINE AND SIMULATORS DEVICES

SIMULATIONS MEANS A TECH NICAL MODEL OF REALITY THAT ALLOWS TO ASSESS AND PREDICT THE UNFOLDING DYNAMIC OF A SERIES OF EVENTS SUBSEQUENT TO IMPOSITION OF CERTAIN CONDITIONS BY THE ANALYST OR THE USER

Unique syndio-selectivity in CO/styrene copolymerization reaction catalyzed by palladium complexes with 2-(2\u2032-oxazolinyl)-1,10-phenanthrolines

The reaction of the neutral Pd complex [Pd(CH3)Cl(cod)] with the potentially terdentate 2-oxazolinyl phenanthroline ligands 1-3 affords the corresponding cationic dinuclear Pd-complexes 1a-3a which can be isolated in the solid state in good yields. By treatment with AgPF6 the complexes 1a-3a were converted into the corresponding hexafluorophosphate derivatives 1b-3b where both the ligand units feature a terdentate coordination around the two Pd-centres with the phenanthroline fragment of each unit displaying a chelate coordination to one Pd-centre while the corresponding oxazolinyl pendant acts as a bridging ligand towards the second Pd-centre. The persistence of this dimeric structure of 1b-3b in CD2Cl2 solution is confirmed by 15N-NMR experiments at natural abundance, which clearly show the binding to the metal of all the nitrogen donors as well as the overall C2 symmetry of the compound. In consequence of the different strength of the relevant ion-pair, the dimeric structure of the complex undergoes partial fragmentation in the case of the chloride derivatives 1a-3a as evidenced from the 15N-NMR spectra. Complexes 1b-3b are active catalysts in styrene alternate carbonylation, where, under very mild conditions (30 \ub0C and 1 atm of CO), they provide oligomers with 3-5 repetitive units as the exclusive or prevailing product. When traces of the CO/styrene polyketones are also formed, their 13C-NMR characterization shows that they are stereochemically homogeneous with a unique syndio-tacticity. This result implies that Pd-complexes able to induce a complete enantioface discrimination in the insertion step of the alkene during the catalytic cycle of the styrene alternate carbonylation have been produced for the first time