An Effective Liposome-Based Nanodelivery System for Naphthalene Derivative Polyamines with Antitumor Activity.

This study focuses on the development of a novel liposome-based nanodelivery system designed to encapsulate polyamine-1, a compound with potential anti-tumor properties. The main objective of this work was to enhance the therapeutic and imaging potential of polyamine-1 by incorporating it into liposome-based nanoparticles, which were functionalized with a gadolinium complex for imaging purposes and a fluorescent phospholipid for tracking applications. These nanoparticles were characterized by measuring their size, shape, polydispersity index, zeta potential and encapsulation efficiency.

Development of potent tripodal G-quadruplex DNA binders and their efficient delivery to cancer cells by aptamer functionalised liposomes.

Two new ligands (TPB3P and TPB3Py) showing a strong stabilisation effect and good selectivity for G4 over duplex DNAs have been synthesised. The ligands hold three analogous polyamine pendant arms (TPA3P and TPA3Py) but differ in the central aromatic core, which is a triphenylbenzene moiety instead of a triphenylamine moiety. Both TPB3P and TPB3Py exhibit high cytotoxicity in MCF-7, LN229 and HeLa cancer cells in contrast to TPA-based ligands, which exhibit no significant cytotoxicity.

Cucurbituril hosts as promoters of aggregation induced emission of triphenylamine derivatives.

Three ligands bearing triphenylamine as a core and one, two or three acyclic polyamine chains, TPA1p, TPA2p and TPA3p, respectively, have been studied by potentiometric and photophysical (UV-Vis, steady-state and time-resolved fluorescence) techniques. The host-guest interaction with cucurbit[7]uril, CB7, has been investigated in aqueous solution showing aggregation induced emission behaviour when encapsulated into a CB7 cavity. From fluorescence emission it is revealed that the charged polyamine chains are the unit entering into CB7 and from the Job plots the stoichiometries are found to vary from 1 : 1 to 1 : 3 L : CB7 ratios.

Defined D-hexapeptides bind CUG repeats and rescue phenotypes of myotonic dystrophy myotubes in a Drosophila model of the disease.

In Myotonic Dystrophy type 1 (DM1), a non-coding CTG repeats rare expansion disease; toxic double-stranded RNA hairpins sequester the RNA-binding proteins Muscleblind-like 1 and 2 (MBNL1 and 2) and trigger other DM1-related pathogenesis pathway defects. In this paper, we characterize four D-amino acid hexapeptides identified together with abp1, a peptide previously shown to stabilize CUG RNA in its single-stranded conformation. With the generalized sequence cpy(a/t)(q/w)e, these related peptides improved three MBNL-regulated exon inclusions in DM1-derived cells.

Cluster dirhenium(III) cis-dicarboxylates with α-amino acids ligands as mighty selective G4s binders.

The synthesis of four dirhenium(III) cis-dicarboxylates with the α-amino acids residues Asp (I), Glu (II), Phe (III) and Tyr (IV) is presented. The G-quadruplex stabilization potential was evaluated by fluorescence resonance energy transfer - melting analysis. All derivatives show specific binding to c-kit1 quadruplex, while II and IV have also strong stabilization activity to HTelo21 quadruplex.

Zn and Cu complexes of a fluorescent scorpiand-type oxadiazole azamacrocyclic ligand: crystal structures, solution studies and optical properties.

A ligand comprised of a macrocyclic pyridinophane core having a pendant arm containing a secondary amine group linked through a methylene spacer to a pyridyl-oxadiazole-phenyl (PyPD) fluorescent system has been prepared (L). The crystal structures of [ZnL](ClO) and [CuL](ClO) show that M is coordinated to all the nitrogen atoms of the macrocyclic core, the secondary amine of the pendant arm and the nitrogen atom of the pyridine group of the fluorescent moiety, the latter bond being clearly weaker than the one with the pyridine of the macrocycle. Solution studies showed the formation of a highly stable Cu complex with 1 : 1 stoichiometry, whereas with Zn least stable complexes were formed and, given the right conditions, a [ZnL] species was also detected, but it was not possible to isolate this species in the solid state.

Aza-Macrocyclic Triphenylamine Ligands for G-Quadruplex Recognition.

A new series of triphenylamine-based ligands with one (TPA1PY), two (TPA2PY) or three pendant aza-macrocycle(s) (TPA3PY) has been synthesised and studied by means of pH-metric titrations, UV/Vis spectroscopy and fluorescence experiments. The affinity of these ligands for G-quadruplex (G4) DNA and the selectivity they show for G4s over duplex DNA were investigated by Förster resonance energy transfer (FRET) melting assays, fluorimetric titrations and circular dichroism spectroscopy. Interestingly, the interactions of the bi- and especially the tri-branched ligands with G4s lead to a very intense redshifted fluorescence emission band that may be associated with intermolecular aggregation between the molecule and DNA.

Anti-angiogenic drug loaded liposomes: Nanotherapy for early atherosclerotic lesions in mice.

Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were divided into several groups to test the efficacy of this anti-angiogenic drug for early treatment of atherosclerotic lesions. Statistical analysis of the lesions revealed a decrease in the lesion size after 5 weeks of treatment.

Binding Mode and Selectivity of a Scorpiand-Like Polyamine Ligand to Single- and Double-Stranded DNA and RNA: Metal- and pH-Driven Modulation.

The interaction of a polyazacyclophane ligand having an ethylamine pendant arm functionalized with an anthryl group (L), with the single-stranded polynucleotides polyA, polyG, polyU, and polyC as well as with the double-stranded polynucleotides polyA-polyU, poly(dAT) , and poly(dGC) has been followed by UV/Vis titration, steady state fluorescence spectroscopy, and thermal denaturation measurements. In the case of the single-stranded polynucleotides, the UV/Vis and fluorescence titrations permit to distinguish between sequences containing purine and pyrimidine bases. For the double-stranded polynucleotides the UV/Vis measurements show for all of them hypochromicity and bathochromic shifts.

Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder.

The safety and efficacy of sertraline versus placebo were examined in a group of nondepressed outpatients with obsessive-compulsive disorder (OCD). Patients with moderate-to-severe OCD were recruited at 10 sites. After a 1-week placebo lead-in, patients were treated in a double-blind fashion for 12 weeks with sertraline or placebo.