An integrated approach for the systematic evaluation of polymeric nanoparticles in healthy and diseased organisms

Innovative strategies that utilize nanoparticles (NPs) for a better delivery of drugs and to improve their therapeutic efficacy have been widely studied in many clinical fields, including oncology. To develop safe and reliable devices able to reach their therapeutic target, a hierarchical characterization of NP interactions with biological fluids, cells, and whole organisms is fundamental. Unfortunately, this aspect is often neglected and the development of standardized characterization methods would be of fundamental help to better elucidate the potentials of nanomaterials, even before the loading of the drugs. Here, we propose a multimodal in vitro/in vivo/ex vivo platform aimed at evaluating these interactions for the selection of the most promising NPs among a wide series of materials. To set the system, we used non-degradable fluorescent poly(methyl-methacrylate) NPs of different sizes (50, 100, and 200 nm) and surface charges (positive and negative). First we studied NP stability in biological fluids. Then, we evaluated NP interaction with two cell lines of triple-negative breast cancer (TNBC), 4T1, and MDA-MB231.1833, respectively. We found that NPs internalize in TNBC cells depending on their physico-chemical properties without toxic effects. Finally, we studied NP biodistribution in terms of tissue migration and progressive clearance in breast-cancer bearing mice. The use of highly stable poly(methyl-methacrylate) NPs enabled us to track them for a long time in cells and animals. The application of this platform to other nanomaterials could provide innovative suggestions for the development of a systematic method of characterization to select the most reliable nanodrug candidates for biomedical applications.     

Low-redshift formula for the luminosity distance in a LTB model with cosmological constant

We calculate the low-redshift Taylor expansion for the luminosity distance for an observer at the center of a spherically symmetric matter inhomogeneity with a non-vanishing cosmological constant. We then test the accuracy of the formulas comparing them to the numerical calculation for different cases for both the luminosity distance and the radial coordinate. The formulas can be used as a starting point to understand the general non-linear effects of a local inhomogeneity in the presence of a cosmological constant, without making any special assumption as regards the inhomogeneity profile.     

The Preparation of β-Hydroxysulfoxides

. Oxidation of β-hydroxy thioethers with MnO₂-aqu. 35%/HCl in methanol gives β-hydroxy sulfoxides in high yields.     

Palladium‐Catalyzed Migratory Insertion of Isocyanides: An Emerging Platform in Cross‐Coupling Chemistry

Isocyanides have been important building blocks in organic synthesis since the discovery of the Ugi reaction and related isocyanide‐based multicomponent reactions. In the past decade isocyanides have found a new application as versatile C₁ building blocks in palladium catalysis. Palladium‐catalyzed reactions involving isocyanide insertion offer a vast potential for the synthesis of nitrogen‐containing fine chemicals. This Minireview discusses all the achievements in this emerging field.     

Non-destructive determination of the silver content in Roman coins (nummi), dated to 308–311 A.D., by the combined use of PIXE-alpha, XRF and DPAA techniques

In the last years a non-destructive protocol of analysis, based on the combined use of the portable PIXE-alpha (particles induced X-ray emission), the XRF (X-ray florescence) spectrometers and of the new DPAA (deep protons activation analysis) method, was developed at the LANDIS laboratory of the INFN-LNS and IBAM-CNR, in order to characterise late Roman nummi dating from 294 onwards. The main aim of the investigation was the determination of the silver content of the coins produced in different periods of time and the study of the technique used for their manufacturing.The present paper discusses the results obtained from the analysis of 15 coins dated back to 308–311 A.D. produced at Carthago during the domination of the usurper L. Domitius Alexander. The obtained analytical data allowed to make some considerations about the minting of silvered bronze coins during this historical period.     

Metal-free intermolecular oxidative C-N bond formation via tandem C-H and N-H bond functionalization

The development of a novel intermolecular oxidative amination reaction, a synthetic transformation that involves the simultaneous functionalization of both a N-H and C-H bond, is described. The process, which is mediated by an I(III) oxidant and contains no metal catalysts, provides a rapid and green method for synthesizing protected anilines from simple arenes and phthalimide. Mechanistic investigations indicate that the reaction proceeds via nucleophilic attack of the phthalimide on an aromatic radical cation, as opposed to the electrophilic aromatic amination that has been reported for other I(III) amination reactions. The application of this new reaction to the synthesis of a variety of substituted aniline derivatives is demonstrated.     

Defect detection and localization in orthotropic wood slabs by inversion of dynamic surface displacements

The nondestructive evaluation inversion and generalized force-mapping techniques developed and demonstrated for isotropic thin plates by Bucaro et al. [(2004). "Detection and localization of inclusions in plates using inversion of point actuated surface displacements," J. Acoust. Soc. Am. 115, 201-206] are extended to the case of orthotropic plates. The extended techniques are applied to a finite-element generated numerical database for point excited wooden slabs with and without an internal defect at 5 and 10 kHz. Operation of the original isotropic algorithms on the wood surface displacements is shown to fail in recovering the uniform elastic parameters or in detecting and locating the defect. The new algorithms based on the wave equation for a thin, orthotropic plate successfully convert the surface displacements on the uniform wooden slab to elastic parameter maps which serve to detect and localize the defect in the flawed plate. The results, particularly at the higher frequency, indicate that the onset of failure in the thin plate approximation impacts both the inversion and the generalized force-mapping accuracy. However, in this case use of the inversion algorithm to obtain modified wave equation coefficients followed by operation of the force-mapping algorithm with these new parameters inserted is shown to successfully mitigate this effect.     

Microstructuring of diamond bulk by IR femtosecond laser pulses

We report the fabrication of graphitic microstructures in the bulk of chemical vapor deposited (CVD) diamond using 120-fs laser pulses at 800-nm wavelength. The nature of the laser-modified region and generation of mechanical stresses in the surrounding diamond is studied with Raman spectroscopy. A spontaneous growth of the laser-modified region from the focal plane towards the laser has been visualized in the process of multipulse irradiation with different pulse energies. The formation of discrete or continuous graphitized structures is revealed depending on the varied local laser intensity. The physical processes governing the appearance of separate graphitic globules and continuous extension of the graphitized region are discussed. Controlling the laser irradiation conditions permits us to fabricate graphitic wires with typical length of 150 μm and diameter of 1.5 μm. The longer, 300-ps pulses, as applied to laser microstructuring of the CVD diamond bulk, are found to be inappropriate due to the stronger influence of structural defects on the damage threshold, the noticeable fluctuation of the structure diameter over the length and the pronounced cracking of the surrounding diamond. PACS 42.62.-b; 61.80.Ba     

Zinc oxide nanostructures grown by pulsed laser deposition

We report the use of PLD to grow different ZnO nanostructures. Very different film morphologies have been observed using different laser wavelengths to ablate the target. The influence of substrate temperature and oxygen background pressure on the film morphology has been investigated too. Smooth and rough films, hexagonal pyramids and columns have been obtained by using a KrF excimer laser (248 nm) for the target ablation, while hexagonal hierarchical structures and pencils have been obtained by using ArF (193 nm). Photoluminescence and X-ray diffraction measurements revealed the good quality of the samples, in particular of those deposited using the ArF laser beam.     

Pole approximation in the quasi-free t + p scattering and the t(p,d)d reaction via the t + d interaction

The t(p,p)t and t(p,d)d channels have been investigated in an indirect way through the ²H(t,tp)n and ²H(t,dd)n three-body reactions performed at E _t = 35.5?MeV in quasi-free kinematics. The agreement with direct data supports the pole approximation at energies above the Coulomb barrier.