MicroRNAs delivery into human cells grown on 3D-printed PLA scaffolds coated with a novel fluorescent PAMAM dendrimer for biomedical applications.

Many advanced synthetic, natural, degradable or non-degradable materials have been employed to create scaffolds for cell culture for biomedical or tissue engineering applications. One of the most versatile material is poly-lactide (PLA), commonly used as 3D printing filament. Manufacturing of multifunctional scaffolds with improved cell growth proliferation and able to deliver oligonucleotides represents an innovative strategy for controlled and localized gene modulation that hold great promise and could increase the number of applications in biomedicine. Here we report for the first time the synthesis of a novel Rhodamine derivative of a poly-amidoamine dendrimer (G = 5) able to transfect cells and to be monitored by confocal microscopy that we also employed to coat a 3D-printed PLA scaffold. The coating do not modify the oligonucleotide binding ability, toxicity or transfection properties of the scaffold that is able to increase cell proliferation and deliver miRNA mimics (i.e., pre-mir-503) into human cells. Although further experiments are required to optimize the dendrimer/miRNA ratio and improve transfection efficiency, we demonstrated the effectiveness of this promising and innovative 3D-printed transfection system to transfer miRNAs into human cells for future biomedical applications.

Solution and Solid-State Studies on the Halide Binding Affinity of Perfluorophenyl-Armed Uranyl-Salophen Receptors Enhanced by Anion-π Interactions.

The enhancement of the binding between halide anions and a Lewis acidic uranyl-salophen receptor has been achieved by the introduction of pendant electron-deficient arene units into the receptor skeleton. The association and the occurrence of the elusive anion-π interaction with halide anions (as tetrabutylammonium salts) have been demonstrated in solution and in the solid state, providing unambiguous evidence on the interplay of the concerted interactions responsible for the anion binding.

Characterization of naproxen-polymer conjugates for drug-delivery.

The synthesis and the characterization of three new naproxen decorated polymers are described. A versatile and general approach is employed to link the drug to polymers, affording the derivatives with a very high degree of purity. The release of the drug from the conjugates proved to be exceptionally slow, even in acidic aqueous media, and the kinetic of the process seems to be triggered by their solubility in water. On the other hand, the interesting outcome of the first ex vivo drug release experiments on human blood samples makes this preliminary study valuable for future investigations on the use of these polymeric prodrugs in in vivo treatment of inflammatory states.

Fluoride binding in water with the use of micellar nanodevices based on salophen complexes.

The use of micelles to transpose lipophilic receptors, such as uranyl-salophen complexes, into an aqueous environment is a valuable and versatile tool. Receptor 1 incorporated into CTABr micelles forms a supramolecular system that exhibits excellent binding properties towards fluoride in water, despite the competition of the aqueous medium. To fully evaluate the potential of micellar nanodevices, we extended our previous study to other types of surfactants and to a uranyl-salophen receptor with a more extended aromatic surface. Paramagnetic relaxation enhancement experiments were used to obtain information on the location of the two receptors within the micelles and complementary information was obtained from dynamic light scattering experiments. With these data it is possible to account for the key factors necessary to obtain an efficient supramolecular device for anion binding in water.

Anion recognition by uranyl-salophen derivatives as probed by infrared multiple photon dissociation spectroscopy and ab initio modeling.

The vibrational features and molecular structures of complexes formed by a series of uranyl-salophen receptors with simple anions, such as Cl(-) , H(-) , and HCOO(-) , have been investigated in the gas phase. Spectra of the anionic complexes were studied in the $\tilde \nu $=800-1800 cm(-1) range by mass-selective infrared multiple photon dissociation (IRMPD) spectroscopy with a continuously tunable free-electron laser. The gas-phase decarboxylation of the formate adducts produces uranyl-salophen monohydride anions, which have been characterized for the first time and reveal a strong UH bond, the nature of which has been elucidated theoretically. The spectra are in excellent agreement with the results obtained from high-quality ab initio calculations, which provided the structure and binding features of the anion-receptor complexes.

Orthohalogen substituents dramatically enhance hydrogen bonding of aromatic ureas in solution.

The phenylurea moiety is a ubiquitous synthon in supramolecular chemistry. Here we report that the introduction of chlorine or bromine atoms in the ortho positions to the urea unit is a simple and very efficient way to improve its intermolecular hydrogen bond (HB) donor character. This effect was demonstrated in solution both in the context of self-association of bis-ureas and hydrogen bonding of mono-ureas to strong HB acceptors.

Substituent effects on the biological properties of Zn-salophen complexes.

The synthesis, characterization, and luminescent properties of a series of 5,5'-X-substituted salophen ligands, X = OCH3, Br, and NO2, and the corresponding Zn(II) complexes are reported here. Their biological activity has been analyzed and related to the different Lewis acid character of the complexes. In vitro studies (AFM and absorption and emission titrations) show that the strongest interaction with free plasmid DNA is observed for 5,5'-dinitro-substituted Zinc-salophen complex 3b. Semiempirical theoretical calculations together with redox potential measurements suggest that this might be interpreted as a direct consequence of this compound having the hardest Lewis acid character. Cellular uptake and cytotoxicity studies undertaken with these metal complexes show that they enter the cells but are not cytotoxic.

Kinetics of demetallation of a zinc-salophen complex into liposomes.

A Zn-salophen complex has been incorporated into POPC large unilamellar liposomes (LUV) obtained in phosphate buffer at pH 7.4. Fluorescence optical microscopy and anisotropy measurements show that the complex is located at the liposomal surface, close to the polar headgroups. The interaction of the POPC phosphate group with Zn(2+) slowly leads to demetallation of the complex. The process follows first order kinetics and rate constants have been measured fluorimetrically in pure water and in buffered aqueous solution. The coordination of the phosphate group of monomeric POPC with salophen zinc also occurs in chloroform as detected by ESI-MS measurements. The effect of the Zn-salophen complex on the stability of POPC LUV has been evaluated at 25°C by measuring the rate of release of entrapped 5(6)-carboxyfluorescein (CF) in the presence and in the absence of Triton X-100 as the perturbing agent. It turns out that the inclusion of the complex significantly increases the stability of POPC LUV.