Nutraceutics is a growing research field in which researchers study and attempt to improve the biological properties of metabolites in food. Wine is one of the most consumed products in the world and contains a plethora of molecules biologically relevant to human health. In this article, several polyphenols with potential antioxidant activity were measured in wines from Apulia, in Southeast Italy. Hydroxytyrosol, gallic and syringic acids, luteolin, quercetin, and trans-resveratrol were identified and quantified by HPLC. The amount of the analyzed metabolites in wines were largely dependent on their color, with red ones being the richest compared to white and rose wines. Gallic acid was the most abundant polyphenol, followed by syringic acid and luteolin. Nevertheless, significant amounts of hydroxytyrosol, quercetin, and trans-resveratrol were also found. The average concentration of polyphenols found in these wines could have potential health-promoting effects, especially if consumed in moderate quantities on a regular basis.

Halloysite Nanotubes (HNTs) are nanomaterials composed of double layered aluminosilicate minerals with a predominantly hollow tubular structure in submicron range. HNTs are characterized by a wide range of applications in anticancer therapy, sustained agent delivery, being particularly interesting because of their tunable release rates and fast adsorption rates. However systematic investigations of their acoustic properties are still poorly documented. This paper shows a quantitative assessment of the effectiveness of HNTs as scatterers at conventional ultrasonic frequencies (5.7 -7 MHz) in low range of concentrations (1.5-5 mg/mL). Different samples of HNT (diameter: 40-50 nm; length: 0.5 to 2 microns, empty lumen diameter: 15-20 nm) containing agarose gel were imaged through a commercially available echographic system and acquired data were processed through a dedicated prototypal platform in order to extract the average ultrasonic signal amplitude associated to the considered sample. Relationships have been established among backscatter, HNT concentration and the employed echographic frequency. Our results demonstrated that improvement in image backscatter could be achieved incrementing HNT concentration, determining a non-linear signal enhancement due to the fact that they are poly-disperse in length. On the other hand the effect of different echographic frequencies used was almost constant at all concentrations, specifically using higher values of echographic frequency allows yielding a signal enhanced of a factor 1.75±0.26.

Extra-virgin olive oil (EVOO) is among the basic constituents of the Mediterranean diet. Its nutraceutical properties are due mainly, but not only, to a plethora of molecules with antioxidant activity known as biophenols. In this article, several biophenols were measured in EVOOs from South Apulia, Italy. Hydroxytyrosol, tyrosol and their conjugated structures to elenolic acid in different forms were identified and quantified by high performance liquid chromatography (HPLC) together with lignans, luteolin and α-tocopherol. The concentration of the analyzed metabolites was quite high in all thecultivarsstudied, but it was still possible to discriminate them through multivariate statistical analysis (MVA). Furthermore, principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were also exploited for determining variances among samples depending on the interval time between harvesting and milling, on the age of the olive trees, and on the area where the olive trees were grown.

To evaluate the diagnostic performance of gold nanorod (GNR)-enhanced optoacoustic imaging employing a conventional echographic device and to determine the most effective operative configuration in order to assure optoacoustic effectiveness, nanoparticle stability, and imaging procedure safety. The most suitable laser parameters were experimentally determined in order to assure nanoparticle stability during the optoacoustic imaging procedures. The selected configuration was then applied to a novel tissue-mimicking phantom, in which GNR solutions covering a wide range of low concentrations (25-200 pM) and different sample volumes (50-200 μL) were exposed to pulsed laser irradiation. GNR-emitted optoacoustic signals were acquired either by a couple of single-element ultrasound probes or by an echographic transducer. Off-line analysis included: (a) quantitative evaluation of the relationships between GNR concentration, sample volume, phantom geometry, and amplitude of optoacoustic signals propagating along different directions; (b) echographic detection of "optoacoustic spots," analyzing their intensity, spatial distribution, and clinical exploitability. MTT measurements performed on two different cell lines were also used to quantify biocompatibility of the synthesized GNRs in the adopted doses. Laser irradiation at 30 mJ/cm(2) for 20 seconds resulted in the best compromise among the requirements of effectiveness, safety, and nanoparticle stability. Amplitude of GNR-emitted optoacoustic pulses was proportional to both sample volume and concentration along each considered propagation direction for all the tested boundary conditions, providing an experimental confirmation of isotropic optoacoustic emission. Average intensity of echographically detected spots showed similar behavior, emphasizing the presence of an "ideal" GNR concentration (100 pM) that optimized optoacoustic effectiveness. The tested GNRs also exhibited high biocompatibility over the entire considered concentration range. An optimal configuration for GNR-enhanced optoacoustic imaging was experimentally determined, demonstrating in particular its feasibility with a conventional echographic device. The proposed approach can be easily extended to quantitative performance evaluation of different contrast agents for optoacoustic imaging.

Nanosized particles are receiving increasing attention as future contrast agents (CAs) for ultrasound (US) molecular imaging, possibly decorated on its surface with biological recognition agents for targeted delivery and deposition of therapeutics. In particular, silica nanospheres (SiNSs) have been demonstrated to be feasible in terms of contrast enhancement on conventional US systems. In this work, we evaluated the cytotoxicity of SiNSs on breast cancer (MCF-7) and HeLa (cervical cancer) cells employing NSs with sizes ranging from 160 to 330 nm and concentration range of 1.5-5 mg/mL. Cell viability was evaluated in terms of size, dose and time dependence, performing the MTT reduction assay with coated and uncoated SiNSs. Whereas uncoated SiNSs caused a variable significant decrease in cell viability on both cell lines mainly depending on size and exposure time, PEGylated SiNSs (SiNSs-PEG) exhibit a high level of biocompatibility. In fact, after 72-h incubation, viability of both cell types was above the cutoff value of 70 % at concentration up to 5 mg/ mL. We also investigated the acoustical behavior of coated and uncoated SiNSs within conventional diagnostic US fields in order to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable CAs. Our results indicate that the employment of SiNSs with diameters around 240 nm assures the most effective contrast enhancement even at the lowest tested concentration, coupled with the possibility of targeting all tumor tissues, being the SiNSs still in a size range where reticuloendothelial system trapping effect is relatively low.

Photoacoustic (PA) imaging is based on the detection of ultrasound signals emitted by physiological targets that underwent a pulsed laser irradiation. Gold nanoparticles are being currently studied by several research groups as potential molecular contrast agents for PA imaging. Aim of this paper was to test whether a highly biocompatible PEG (polyethylene glycol) coating can improve the stability of gold nanorods (GNRs) under laser irradiation and their effectiveness as contrast agents for PA imaging with respect to uncoated GNRs. Uncoated GNRs and PEG-coated GNRs were synthesized with the same size (48x7 nm) and very similar absorption spectra (main peak at 1055 nm). GNR stability was evaluated as a function of both laser fluence (range 40-100 mJ/cm2) and exposure duration (30-60 s), monitoring optical and morphological GNR changes. PA effectiveness was then tested using a custom-designed phantom which allowed laser irradiation of GNR solutions of variable concentration contained in a tissue-mimicking hydrogel and acquisition of the corresponding PA signals through a clinically-available ultrasound device. Obtained results showed that absorption spectrum of uncoated GNRs was significantly deteriorated after laser exposure already in the mildest adopted conditions (30-s exposure to 40-mJ/cm2 laser), while PEG-coated GNRs always resulted much more stable, with negligible peak intensity decrements in the mildest irradiation conditions. TEM analysis confirmed the higher morphological stability of PEG-coated GNRs, which also resulted more effective as PA contrast enhancers, since their PA signal intensity was always significantly higher than the corresponding value measured for uncoated GNRs.

The aim of the present work was to demonstrate the possibility of selective detection of nanoparticle contrast agents (NPCAs) on diagnostic echographic images by exploiting the second harmonic component they introduce in the spectra of corresponding ultrasound signals, as a consequence of nonlinear distortion during ultrasound propagation. We employed silica nanospheres (SiNSs) of variable diameter (160 nm, 330 nm, and 660 nm) dispersed in different volume concentrations (range 0.07–0.8%) in agarose gel samples that were automatically scanned through a digital ecograph using narrow-band ultrasound pulses at 6.6 MHz and variable mechanical index (MI range 0.2–0.6).

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To experimentally investigate the acoustical behavior of different dual-mode nanosized contrast agents (NPCAs) for echographic medical imaging at low ultrasound (US) frequency.

A simple and efficient method for synthesizing a range of hybrid nanocomposites based on a core of silica nanospheres (160, 330, and 660 nm in diameter) covered by an outer shell of superparamagnetic nanoparticles, either iron oxide or heterodimeric FePt-iron oxide nanocrystals, is presented. The magnetic and ultrasound characterization of the resulting nanocomposites shows that they have great potential as contrast agents for dual-mode imaging purposes, combining magnetic resonance imaging (MRI) and ultrasonography (US).

Trifunctional polymer nanobeads are prepared by destabilization of a mixture of magnetic nanoparticles, quantum dots, and an amphiphilic polymer, followed by functionalization of the bead surface with folic acid molecules. The distribution of the nanoparticles within the nanobeads can be tuned using either acetonitrile or water as destabilizing solvent. The luminescence of the resulting beads can be tuned by varying the ratio of quantum dots per magnetic nanoparticles. The application of an external magnetic field (such as a small static magnet of 0.3 T) to the magnetic-fluorescent nanobeads allows the quantitative accumulation of the beads within a few hours depending on the total size of the beads. Furthermore, specific targeting of cancer cells overexpressing folate receptors is achieved thanks to the folic acid decorating the surface of the as-synthesized nanobeads. Folate receptor mediated cellular uptake of the folic acid-functionalized nanobeads is proven via both confocal imaging and transmission electron microscopy characterization. Cell sorting experiments performed with trifunctional nanobeads show quantitative recovering of targeted cells even when they are present at low percentage (up to 1%).

Halloysite nanotubes (HNTs) are nanomaterials composed of double layered aluminosilicate minerals characterized by a wide range of medical applications. Nonetheless, systematic investigations of their imaging potential are still poorly documented. This paper shows a parametric assessment of the effectiveness of HNTs as scatterers for safe ultrasound (US)-based molecular imaging. Quantitative evaluation of average signal enhancement produced by HNTs with varying set up configuration was performed. The influence of different levels of power (20%, 50%, and 80%) of the signal emitted by clinical equipment was determined, to assess the efficacy of different HNT concentrations (1.5, 3, and 5 mg/mL) at conventional ultrasonic frequencies (5.7–7 MHz), even in case of specific limitation regarding US mechanical interaction with target tissues. Different samples of HNT containing agarose gel were imaged through a commercially available echographic system and acquired data were processed through a dedicated prototypal platform to extract the average ultrasonic signal amplitude. The rate of signal enhancement achieved by different concentration values was quantified and the contribution of frequency increment was separately evaluated. Despite influencing the level of mechanical excitation on HNTs and tissues, our results demonstrated how increasing the power of the emitted signal negatively affected the measured backscatter.

The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release.

Chitosan nanoparticles (CS NPs) have been widely exploited for the delivery of various types of drugs due to their biocompatibility, availability, ease of functionalization and other advantages. Nevertheless, despite their wide use, their mechanism of action is not very clear and many aspects still need to be investigated in detail, with only a few studies having studied the behavior of this polymer. We prepared CS NPs encapsulating dopamine (DA) and studied the generation of reactive oxygen species (ROS) and the antioxidant effect of the neurotransmitter in detail. Encapsulation of the drug and its subsequent sustained release significantly reduced the oxidation rate in vitro, thus potentially exerting neuroprotective effects. ROS production in SH-SY5Y cells was investigated through a H2O2 assay, while a deeper study of the enzymatic activity allowed us to determine the significant contribution of both GPx and SOD enzymes in preventing oxidative stress.

To experimentally investigate the acoustical behavior of silica nanoparticles within conventional diagnostic ultrasound fields and to determine a suitable configuration, in terms of particle size and concentration, for their employment as targetable contrast agents. We also assessed the effectiveness of a novel method for automatic detection of targeted silica nanoparticles for future tissue typing applications.