Microplastics accumulation in gastrointestinal tracts of Mullus barbatus and Merluccius merluccius is associated with increased cytokine production and signaling.

There is clear evidence that different marine species can be impacted by microplastic (MP) ingestion accumulating such MPs mainly in the gastrointestinal tract. However, there is still limited knowledge on the consequences of MPs' accumulation in the gut. The present study aims to assess MPs and their potential immunotoxic effects in the digestive tract of two species showing different ecological traits: the red mullet (Mullus barbatus) and the European hake (Merluccius merluccius). Infrared spectroscopy (FTIR-ATR), micro-Raman and electron scanning microscope (SEM) were used to accurately identify the main plastic polymers detected in gut contents. In addition, we investigated the association between MP uptake and intestinal inflammation by evaluating expression and secretion of proinflammatory cytokines. MP abundance ranged from 1 to 20 items/individual in red mullet and from 2 to 15 items/individual in European hake. The majority of ingested MPs were fibers, while the dominant colors were black and blue in both species. Chemical characterization indicated polyethylene and polypropylene as the most common polymer types. Moreover, it was observed that MP abundance was highly positive correlated to cytokines (i.e. interleukin-1ß, 10, and interferon) and antioxidant enzyme (i.e. catalase and superoxide dismutase) transcript levels suggesting ROS generation and an infiltration of immune cells in the gut. Our findings provide evidence that the induction of cytokine-dependent signaling pathways is one aspect of the complex mechanism by which MPs affect the gut system in fish.

Dually Cross-Linked Core-Shell Structure Nanohydrogel with Redox-Responsive Degradability for Intracellular Delivery.

A redox-responsive nanocarrier is a promising strategy for the intracellular drug release because it protects the payload, prevents its undesirable leakage during extracellular transport, and favors site-specific drug delivery. In this study, we developed a novel redox responsive core-shell structure nanohydrogel prepared by a water in oil nanoemulsion method using two biocompatible synthetic polymers: vinyl sulfonated poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-polyethylene glycol-poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate) triblock copolymer, and thiolated hyaluronic acid. The influence on the nanohydrogel particle size and distribution of formulation parameters was investigated by a three-level full factorial design to optimize the preparation conditions. The surface and core-shell morphology of the nanohydrogel were observed by scanning electron microscope, transmission electron microscopy, and further confirmed by Fourier transform infrared spectroscopy and Raman spectroscopy from the standpoint of chemical composition. The redox-responsive biodegradability of the nanohydrogel in reducing environments was determined using glutathione as reducing agent. A nanohydrogel with particle size around 250 nm and polydispersity index around 0.1 is characterized by a thermosensitive shell which jellifies at body temperature and crosslinks at the interface of a redox-responsive hyaluronic acid core via the Michael addition reaction. The nanohydrogel showed good encapsulation efficiency for model macromolecules of different molecular weight (93% for cytochrome C, 47% for horseradish peroxidase, and 90% for bovine serum albumin), capacity to retain the peroxidase-like enzymatic activity (around 90%) of cytochrome C and horseradish peroxidase, and specific redox-responsive release behavior. Additionally, the nanohydrogel exhibited excellent cytocompatibility and internalization efficiency into macrophages. Therefore, the developed core-shell structure nanohydrogel can be considered a promising tool for the potential intracellular delivery of different pharmaceutical applications, including for cancer therapy.

Silver Nanoparticle-Based Sensor for the Selective Detection of Nickel Ions.

Silver nanoparticles (AgNPs) can be used as a surface plasmon resonance (SPR) colorimetric sensor; the correlation between the SPR phenomenon and the aggregation state of nanoparticle allows the real-time detection of a target molecule. Surface functionalization of NPs with proper molecular baits is often performed to establish the selectivity of the sensor. This work reports on the synthesis of AgNPs under reducing conditions and on the functionalization thereof with mercaptoundecanoic acid (11-MUA). UV-VIS Spectroscopy confirmed the formation of AgNPs, eliciting a surface plasmon absorption band (SPAB) at 393 nm that shifted to 417 nm upon surface coating. Dynamic light scattering was used to investigate the surface coatings; moreover, pelleted AgNPs@11MUA nanoparticles were characterized by scanning electron microscopy (SEM), energy dispersive X-ray analyzers (EDX), and infrared spectroscopy to corroborate the presence of 11MUA on the surface. Most interestingly, the resulting AgNPs@11MUA selectively detected micromolar levels of Ni2+, also in the presence of other cations such as Mn2+, Co2+, Cd2+, Cu2+, Zn2+, Fe2+, Hg2+, Pb2+, and Cr3+.

Development of a New Hyaluronic Acid Based Redox-Responsive Nanohydrogel for the Encapsulation of Oncolytic Viruses for Cancer Immunotherapy.

Oncolytic viruses (OVs) are emerging as promising and potential anti-cancer therapeutic agents, not only able to kill cancer cells directly by selective intracellular viral replication, but also to promote an immune response against tumor. Unfortunately, the bioavailability under systemic administration of OVs is limited because of undesired inactivation caused by host immune system and neutralizing antibodies in the bloodstream. To address this issue, a novel hyaluronic acid based redox responsive nanohydrogel was developed in this study as delivery system for OVs, with the aim to protect the OVs following systemic administration. The nanohydrogel was formulated by water in oil (W/O) nanoemulsion method and cross-linked by disulfide bonds derived from the thiol groups of synthesized thiolated hyaluronic acid. One DNA OV Ad[I/PPT-E1A] and one RNA OV Rigvir® ECHO-7 were encapsulated into the developed nanohydrogel, respectively, in view of their potential of immunovirotherapy to treat cancers. The nanohydrogels showed particle size of approximately 300-400 nm and negative zeta potential of around -13 mV by dynamic light scattering (DLS). A uniform spherical shape of the nanohydrogel was observed under the scanning electron microscope (SEM) and transmission electron microscope (TEM), especially, the successfully loading of OV into nanohydrogel was revealed by TEM. The crosslinking between the hyaluronic acid chains was confirmed by the appearance of new peak assigned to disulfide bond in Raman spectrum. Furthermore, the redox responsive ability of the nanohydrogel was determined by incubating the nanohydrogel into phosphate buffered saline (PBS) pH 7.4 with 10 µM or 10 mM glutathione at 37 °C which stimulate the normal physiological environment (extracellular) or reductive environment (intracellular or tumoral). The relative turbidity of the sample was real time monitored by DLS which indicated that the nanohydrogel could rapidly degrade within 10 h in the reductive environment due to the cleavage of disulfide bonds, while maintaining the stability in the normal physiological environment after 5 days. Additionally, in vitro cytotoxicity assays demonstrated a good oncolytic activity of OVs-loaded nanohydrogel against the specific cancer cell lines. Overall, the results indicated that the developed nanohydrogel is a delivery system appropriate for viral drugs, due to its hydrophilic and porous nature, and also thanks to its capacity to maintain the stability and activity of encapsulated viruses. Thus, nanohydrogel can be considered as a promising candidate carrier for systemic administration of oncolytic immunovirotherapy.

Band Gap Implications on Nano-TiO2 Surface Modification with Ascorbic Acid for Visible Light-Active Polypropylene Coated Photocatalyst.

The effect of surface modification using ascorbic acid as a surface modifier of nano-TiO2 heterogeneous photocatalyst was studied. The preparation of supported photocatalyst was made by a specific paste containing ascorbic acid modified TiO2 nanoparticles used to cover Polypropylene as a support material. The obtained heterogeneous photocatalyst was thoroughly characterized (scanning electron microscope (SEM), RAMAN, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), photoluminescence (PL), and Diffuse Reflectance Spectra (DRS) and successfully applied in the visible light photodegradation of Alizarin Red S in water solutions. In particular, this new supported TiO2 photocatalyst showed a change in the adsorption mechanism of dye with respect to that of only TiO2 due to the surface properties. In addition, an improvement of photocatalytic performances in the visible light photodegration was obtained, showing a strict correlation between efficiency and energy band gap values, evidencing the favorable surface modification of TiO2 nanoparticles.

Nitroimidazole and glucosamine conjugated heteroscorpionate ligands and related copper(II) complexes. Syntheses, biological activity and XAS studies.

New nitroimidazole and glucosamine conjugated heteroscorpionate ligands, namely 2,2-bis(3,5-dimethyl-1H-pyrazol-1-yl)-N-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)acetamide (L(MN)) and 1,3,4,6-tetra-O-acetyl-2-{[bis(3,5-dimethyl-1H-pyrazol-1-yl)acetyl]amino}-2-deoxy-ß-D-glucopyranose (L(DAC)), respectively, were synthesized by direct coupling of preformed side chain acid and amine components. The related copper(II) complexes {[(L(MN))(2)Cu]Cl(2)}, and {[(L(DAC))(2)Cu]Cl(2)} have been prepared from the reaction of CuCl(2)*2H(2)O with L(MN) or L(DAC) ligand in methanol solution. Single crystal structural characterization was undertaken for the L(MN) ligand. In the absence of a coordinated metal core, the overall arrangement of the ligand is determined by some loose intra- and inter-molecular nonbonding contacts. X-Ray Absorption Spectroscopy (XAS) has been used to probe the local structure of the two copper(II) complexes, {[(L(MN))(2)Cu]Cl(2)} and {[(L(DAC))(2)Cu]Cl(2)}. The EXAFS analysis has permitted the identification of the local environment of the copper site. Copper interacts with 2 units of ligand in both complexes, and it is found to be 6-fold coordinated. Its local structure is described by four Cu-N and two Cu-O interactions to form a pseudo-octahedron core, with a 0.14 Å lengthening of the Cu-O bond length in the case of L(DAC) complex with respect to the L(MN) one, likely due to the higher steric hindrance of the glucosamine moiety. The XANES analysis agrees with these results, also confirming the Cu(II) formal copper oxidation state for both complexes. The new copper(II) complexes {[(L(MN))(2)Cu]Cl(2)} and {[(L(DAC))(2)Cu]Cl(2)} as well as the corresponding uncoordinated ligands were evaluated for their cytotoxic activity towards a panel of several human tumour cell lines. The results reported here indicate that both copper(II) complexes show similar spectra of cytotoxicity and very low resistance factors (RF < 2) against C13* ovarian cancer cells which have acquired resistance to cisplatin.