Semaglutide Modulates Extracellular Matrix Production of LX-2 Cells via Exosomes and Improves Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to some metabolic disorders, such as central obesity and type 2 diabetes (T2D). Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide, may have therapeutic roles in MASLD associated with T2D. This study aims to investigate the molecular mechanisms underlying the effectiveness of semaglutide on MASLD in terms of progression from liver steatosis to fibrosis. We characterized exosomes from ten patients with type 2 diabetes (T2D) before (T0) and after 12 months (T12) of treatment with once-weekly subcutaneous semaglutide. Six of ten patients were considered responders to therapy (R) based on MASLD severity downgrading by at least one class according to a validated ultrasonographic (US) score. Normal hepatocytes (HEPA-RG) and stellate (LX-2) cells were challenged with exosomes from R and NR patients, isolated before and after 12 months of therapy. Exosomes from both R and NR patients isolated at T0 significantly affected LX-2 viability. After 12 months of treatment, only those isolated from R patients restored cell viability, whereas those from NR patients did not. No effects were observed on HEPA-RG cells. Exosomes at T12 from R but not from NR patients significantly decreased the production of α-SMA, a marker of LX-2 activation, a liver stellate cell model, and ph-SMAD2 and CTGF, involved in fibrosis processes. TGF-ß1 was not modulated by the exosomes of R and NR patients. As a downstream effect, Vimentin, Collagen 1A1, and Fibronectin extracellular matrix components were also downregulated, as measured by droplets digital PCR. In conclusion, these results shed light on the potential effectiveness of semaglutide in improving liver fibrosis in MASLD.

Luminescent Alendronic Acid-Conjugated Micellar Nanostructures for Potential Application in the Bone-Targeted Delivery of Cholecalciferol.

Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV-visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future.

Plasma-Derived Exosomes from NAFLD Patients Modulate the Cannabinoid Receptors' Expression in Cultured HepaRG Cells.

Exosomes produced by hepatocytes upon lipotoxic insult play a relevant role in pathogenesis of nonalcoholic fatty liver disease (NAFLD), suggesting an inflammatory response by the activation of monocytes and macrophages and accelerating the disease progression. In the pathogenesis of NAFLD and liver fibrosis, the endogenous cannabinoids and their major receptors CB1 and CB2 appear to be highly involved. This study aimed at evaluating the expression of cannabinoids receptors (CB1R and CB2R) in plasma-derived exosomes extracted from patients with NAFLD, as well as investigating the in vitro effects of the circulating exosomes in cultured human HepaRG cells following their introduction into the culture medium. The results demonstrated that plasma-derived exosomes from NAFLD patients are vehicles for the transport of CB1R and are able to modulate CB receptors' expression in HepaRG cells. In particular, circulating exosomes from NAFLD patients are inflammatory drivers for HepaRG cells, acting through CB1R activation and the downregulation of CB2R. Moreover, CB1R upregulation was associated with increased expression levels of PPAR-γ, a well-known mediator of liver tissue injury. In conclusion, this study provides evidence for CB1R transport by exosomes and suggests that the in vitro effects of circulating exosomes from NAFLD patients are mediated by the expression of cannabinoid receptors.

High Surface Area Mesoporous Silica Nanoparticles with Tunable Size in the Sub-Micrometer Regime: Insights on the Size and Porosity Control Mechanisms.

Mesoporous silica nanostructures (MSNs) attract high interest due to their unique and tunable physical chemical features, including high specific surface area and large pore volume, that hold a great potential in a variety of fields, i.e., adsorption, catalysis, and biomedicine. An essential feature for biomedical application of MSNs is limiting MSN size in the sub-micrometer regime to control uptake and cell viability. However, careful size tuning in such a regime remains still challenging. We aim to tackling this issue by developing two synthetic procedures for MSN size modulation, performed in homogenous aqueous/ethanol solution or two-phase aqueous/ethyl acetate system. Both approaches make use of tetraethyl orthosilicate as precursor, in the presence of cetyltrimethylammonium bromide, as structure-directing agent, and NaOH, as base-catalyst. NaOH catalyzed syntheses usually require high temperature (>80 °C) and large reaction medium volume to trigger MSN formation and limit aggregation. Here, a successful modulation of MSNs size from 40 up to 150 nm is demonstrated to be achieved by purposely balancing synthesis conditions, being able, in addition, to keep reaction temperature not higher than 50 °C (30 °C and 50 °C, respectively) and reaction mixture volume low. Through a comprehensive and in-depth systematic morphological and structural investigation, the mechanism and kinetics that sustain the control of MSNs size in such low dimensional regime are defined, highlighting that modulation of size and pores of the structures are mainly mediated by base concentration, reaction time and temperature and ageing, for the homogenous phase approach, and by temperature for the two-phase synthesis. Finally, an in vitro study is performed on bEnd.3 cells to investigate on the cytotoxicity of the MNSs.

Gold-Speckled SPION@SiO2 Nanoparticles Decorated with Thiocarbohydrates for ASGPR1 Targeting: Towards HCC Dual Mode Imaging Potential Applications.

Efforts are made to perform an early and accurate detection of hepatocellular carcinoma (HCC) by simultaneous exploiting multiple clinically non-invasive imaging modalities. Original nanostructures derived from the combination of different inorganic domains can be used as efficient contrast agents in multimodal imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) and Au nanoparticles (NPs) possess well-established contrasting features in magnetic resonance imaging (MRI) and X-ray computed tomography (CT), respectively. HCC can be targeted by using specific carbohydrates able to recognize asialoglycoprotein receptor 1 (ASGPR1) overexpressed in hepatocytes. Here, two different thiocarbohydrate ligands were purposely designed and alternatively conjugated to the surface of Au-speckled silica-coated SPIONs NPs, to achieve two original nanostructures that could be potentially used for dual mode targeted imaging of HCC. The results indicated that the two thiocarbohydrate decorated nanostructures possess convenient plasmonic/superparamagnetic properties, well-controlled size and morphology and good selectivity for targeting ASGPR1 receptor.

A Possible Role of FZD10 Delivering Exosomes Derived from Colon Cancers Cell Lines in Inducing Activation of Epithelial-Mesenchymal Transition in Normal Colon Epithelial Cell Line.

Exosomes belong to the family of extracellular vesicles released by every type of cell both in normal and pathological conditions. Growing interest in studies indicates that extracellular vesicles, in particular, the fraction named exosomes containing lipids, proteins and nucleic acid, represent an efficient way to transfer functional cargoes between cells, thus combining all the other cell-cell interaction mechanisms known so far. Only a few decades ago, the involvement of exosomes in the carcinogenesis in different tissues was discovered, and very recently it was also observed how they carry and modulate the presence of Wnt pathway proteins, involved in the carcinogenesis of gastrointestinal tissues, such as Frizzled 10 protein (FZD10), a membrane receptor for Wnt. Here, we report the in vitro study on the capability of tumor-derived exosomes to induce neoplastic features in normal cells. Exosomes derived from two different colon cancer cell lines, namely the non-metastatic CaCo-2 and the metastatic SW620, were found to deliver, in both cases, FZD10, thus demonstrating the ability to reprogram normal colonic epithelial cell line (HCEC-1CT). Indeed, the acquisition of specific mesenchymal characteristics, such as migration capability and expression of FZD10 and markers of mesenchymal cells, was observed. The exosomes derived from the metastatic cell line, characterized by a level of FZD10 higher than the exosomes extracted from the non-metastatic cells, were also more efficient in stimulating EMT activation. The overall results suggest that FZD10, delivered by circulating tumor-derived exosomes, can play a relevant role in promoting the CRC carcinogenesis and propagation.

Exosomes for Diagnosis and Therapy in Gastrointestinal Cancers.

Exosomes are membrane-bound extracellular vesicles (EVs) released by most cells, having a size ranging from 30 to 150 nm, and are involved in mechanisms of cell-cell communication in physiological and pathological tissues. Exosomes are engaged in the transport of biomolecules, such as lipids, proteins, messenger RNAs, and microRNA, and in signal transmission through the intercellular transfer of components. In the context of proteins and nucleic acids transported from exosomes, our interest is focused on the Frizzled proteins family and related messenger RNA. Exosomes can regenerate stem cell phenotypes and convert them into cancer stem cells by regulating the Wnt pathway receptor family, namely Frizzled proteins. In particular, for gastrointestinal cancers, the Frizzled protein involved in those mechanisms is Frizzled-10 (FZD-10). Currently, increasing attention is being devoted to the protein and lipid composition of exosomes interior and membranes, representing profound knowledge of specific exosomes composition fundamental for their application as new delivering drug tools for cancer therapy. This review intends to cover the most recent literature on the use of exosome vesicles for early diagnosis, follow-up, and the use of these physiological nanovectors as drug delivery systems for gastrointestinal cancer therapy.

Flavonoid and Non-Flavonoid Compounds of Autumn Royal and Egnatia Grape Skin Extracts Affect Membrane PUFA's Profile and Cell Morphology in Human Colon Cancer Cell Lines.

Grapes contain many flavonoid and non-flavonoid compounds with anticancer effects. In this work we fully characterized the polyphenolic profile of two grape skin extracts (GSEs), Autumn Royal and Egnatia, and assessed their effects on Polyunsaturated Fatty Acid (PUFA) membrane levels of Caco2 and SW480 human colon cancer cell lines. Gene expression of 15-lipoxygenase-1 (15-LOX-1), and peroxisome proliferator-activated receptor gamma (PPAR-γ), as well as cell morphology, were evaluated. The polyphenolic composition was analyzed by Ultra-High-Performance Liquid Chromatography/Quadrupole-Time of Flight mass spectrometry (UHPLC/QTOF) analysis. PUFA levels were evaluated by gas chromatography, and gene expression levels of 15-LOX-1 and PPAR-γ were analyzed by real-time Polymerase Chain Reaction (PCR). Morphological cell changes caused by GSEs were identified by field emission scanning electron microscope (FE-SEM) and photomicrograph examination. We detected a different profile of flavonoid and non-flavonoid compounds in Autumn Royal and Egnatia GSEs. Cultured cells showed an increase of total PUFA levels mainly after treatment with Autumn Royal grape, and were richer in flavonoids when compared with the Egnatia variety. Both GSEs were able to affect 15-LOX-1 and PPAR-γ gene expression and cell morphology. Our results highlighted a new antitumor mechanism of GSEs that involves membrane PUFAs and their downstream pathways.

PbS Quantum Dots Decorating TiO2 Nanocrystals: Synthesis, Topology, and Optical Properties of the Colloidal Hybrid Architecture.

Fabrication of heterostructures by merging two or more materials in a single object. The domains at the nanoscale represent a viable strategy to purposely address materials' properties for applications in several fields such as catalysis, biomedicine, and energy conversion. In this case, solution-phase seeded growth and the hot-injection method are ingeniously combined to fabricate TiO2/PbS heterostructures. The interest in such hybrid nanostructures arises from their absorption properties that make them advantageous candidates as solar cell materials for more efficient solar light harvesting and improved light conversion. Due to the strong lattice mismatch between TiO2 and PbS, the yield of the hybrid structure and the control over its properties are challenging. In this study, a systematic investigation of the heterostructure synthesis as a function of the experimental conditions (such as seeds' surface chemistry, reaction temperature, and precursor concentration), its topology, structural properties, and optical properties are carried out. The morphological and chemical characterizations confirm the formation of small dots of PbS by decorating the oleylamine surface capped TiO2 nanocrystals under temperature control. Remarkably, structural characterization points out that the formation of heterostructures is accompanied by modification of the crystallinity of the TiO2 domain, which is mainly ascribed to lattice distortion. This result is also confirmed by photoluminescence spectroscopy, which shows intense emission in the visible range. This originated from self-trapped excitons, defects, and trap emissive states.

Green Fluorescent Terbium (III) Complex Doped Silica Nanoparticles.

The low photostability of conventional organic dyes and the toxicity of cadmium-based luminescent quantum dots have prompted the development of novel probes for in vitro and in vivo labelling. Here, a new fluorescent lanthanide probe based on silica nanoparticles is fabricated and investigated for optically traceable in vitro translocator protein (TSPO) targeting. The targeting and detection of TSPO receptor, overexpressed in several pathological states, including neurodegenerative diseases and cancers, may provide valuable information for the early diagnosis and therapy of human disorders. Green fluorescent terbium(III)-calix[4]arene derivative complexes are encapsulated within silica nanoparticles and surface functionalized amine groups are conjugated with selective TSPO ligands based on a 2-phenylimidazo[1,2-a]pyridine acetamide structure containing derivatizable carboxylic groups. The photophysical properties of the terbium complex, promising for biological labelling, are demonstrated to be successfully conveyed to the realized nanoarchitectures. In addition, the high degree of biocompatibility, assessed by cell viability assay and the selectivity towards TSPO mitochondrial membrane receptors, proven by subcellular fractional studies, highlight targeting potential of this nanostructure for in vitro labelling of mitochondria.

Quantum Dot Based Luminescent Nanoprobes for Sigma-2 Receptor Imaging.

The increasing importance of sigma-2 receptor as target for the diagnosis and therapy of tumors paves the way for the development of innovative optically traceable fluorescent probes as tumor cell contrast and therapeutic agents. Here, a novel hybrid organic-inorganic nanostructure is developed by combining the superior fluorescent properties of inorganic quantum dots (QDs), coated with a hydrophilic silica shell (QD@SiO2 NPs), the versatility of the silica shell, and the high selectivity for sigma-2 receptor of the two synthetic ligands, namely, the 6-[(6-aminohexyl)oxy]-2-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl)-3,4-dihydroisoquinolin-1(2H)-one (MLP66) and 6-[1-[3-(4-cyclohexylpiperazin-1-yl)propyl]-1,2,3,4-tetrahydronaphthalen-5-yloxy]hexylamine (TA6). The proposed nanostructures represent a challenging alternative to all previously studied organic small fluorescent molecules, based on the same sigma-2 receptor affinity moieties. Flow cytometry and confocal fluorescence microscopy experiments, respectively, on fixed and living cancerous MCF7 cells, which overexpress the sigma-2 receptor, prove the ability of functionalized (QD@SiO2-TA6 and QD@SiO2-MLP66) NPs to be internalized and demonstrate their affinity to the sigma-2 receptor, ultimately validating the targeting properties conveyed to the NPs by sigma-2 ligand conjugation. The presented QD-based nanoprobes possess a great potential as in vitro selective sigma-2 receptor imaging agent and, consequently, could provide a significant impact to future theranostic applications.

Delivery of Proapoptotic Agents in Glioma Cell Lines by TSPO Ligand-Dextran Nanogels.

Translocator protein 18-kDa (TSPO) is a versatile mitochondrial target for molecular imaging and therapy. Moreover, selective TSPO ligands have been widely investigated for diagnostic purposes and explored to target drug delivery systems directed to cancer cells overexpressing TSPO. Indeed, poly(d,l-lactic-co-glycolic acid (PLGA) polymers and nanocarriers decorated with TSPO ligands are capable of transporting TSPO ligands inside cancer cells, inducing survival inhibition in cancer cells and producing mitochondrial morphology modification. The aim of this work was to prepare nanogels (NGs) made with TSPO ligand dextran conjugates (TSPO-Dex) that are useful as potential delivery systems of two TSPO ligands as apoptotic agents. Synthesis and complete characterization of TSPO-dextran conjugates, an average molecular weights analysis, TSPO ligand release profiles, thermal behaviour and swelling studies were achieved. NG preparation, characterization and in vitro biological studies were also performed. The release of TSPO ligands released from dextran conjugates at 37 °C occurred in human serum at a faster rate than that detected in phosphate buffer. Cytotoxicity studies demonstrated that NGs produced from TSPO ligand-dextran conjugates induce survival inhibition in rat C6 glioma cell lines. Cellular uptake was also proven by fluorescence microscopy.

Spray Dried Chitosan Microparticles for Intravesical Delivery of Celecoxib: Preparation and Characterization.

PURPOSE: Chitosan microparticles containing celecoxib (CB), were developed as chemoprevention of bladder cancer. Furthermore two inclusion complexes of CB with methyl-ß-cyclodextrin (C1 and C2) were prepared to improve the solubility of the drug. METHODS: C1 and C2 were obtained by freeze-drying and characterized in the solid state and in solution. Microparticles loaded with CB or C1 or C2 were prepared by spray drying and fully characterized. RESULTS: The yield and encapsulation efficiencies of microparticles depended by both the viscosity and the presence of the inclusion complex in the feed medium nebulised. Generally, the microparticles exhibited a spherical shape with mean diameter of approximately 2 µm which was compatible with local intravesical administration using a catheter. The CB release studies from the microparticles allowed us to identify both immediate release systems (microparticles including the complexes) and prolonged release systems (microparticles including CB alone). The latter exhibited good adhesion to the bladder mucosa, as highlighted by a mucoadhesion study. Histological studies revealed a desquamation of the superficial cells when the bladder mucosa was treated with microparticles loaded with CB, while the morphology of the urothelium did not change when it was treated with microparticles loaded with the inclusion complex. CONCLUSION: A new CB intravesical formulation than can easily be administered with a catheter and is able to release the drug at the target site for several hours was realized. This new delivery system could be a good alternative to classic oral CB administration.

Fabrication of photoactive heterostructures based on quantum dots decorated with Au nanoparticles.

Silica based multifunctional heterostructures, exhibiting near infrared (NIR) absorption (650-1200 nm) and luminescence in the visible region, represent innovative nanosystems useful for diagnostic or theranostic applications. Herein, colloidal synthetic procedures are applied to design a photoactive multifunctional nanosystem. Luminescent silica (SiO2) coated quantum dots (QDs) have been used as versatile nanoplatforms to assemble on their surface gold (Au) seeds, further grown into Au spackled structures. The synthesized nanostructures combine the QD emission in the visible region, and, concomitantly, the distinctive NIR absorption of Au nanodomains. The possibility of having multiple QDs in a single heterostructure, the SiO2 shell thickness, and the extent of Au deposition onto SiO2 surface have been carefully controlled. The work shows that a single QD entrapped in 16 nm thick SiO2 shell, coated with Au speckles, represents the most suitable geometry to preserve the QD emission in the visible region and to generate NIR absorption from metal NPs. The resulting architectures present a biomedical potential as an effective optical multimodal probes and as promising therapeutic agents due to the Au NP mediated photothermal effect.

Selective confinement of oleylamine capped Au nanoparticles in self-assembled PS-b-PEO diblock copolymer templates.

Amphiphilic polystyrene-block-polyethylene oxide (PS-b-PEO) block copolymers (BCPs) have been demonstrated to be effective in directing organization of colloidal Au nanoparticles (NPs). Au NPs have been incorporated into the polymer and the different chemical affinity between the NP surface and the two blocks of the BCP has been used as a driving force of the assembling procedure. The morphology of the nanocomposites, prepared and fabricated as thin films, has been investigated by means of atomic force and scanning electron microscopies as a function of the NP content and BCP molecular weight. NPs have been effectively dispersed in PS-b-PEO hosts at any investigated content (up to 17 wt%) and a clear effect of the BCP properties on the final nanocomposite morphology has been highlighted. Finally, electrostatic force microscopy has demonstrated the conductive properties of the nanocomposite films, showing that the embedded Au NPs effectively convey their conductive properties to the film. The overall investigation has confirmed the selective confinement of the as-prepared surfactant-coated metal NPs in the PS block of PS-b-PEO, thus proposing a very simple and prompt assembling tool for nanopatterning, potentially suitable for optoelectronic, sensing and catalysis applications.

Unveiling the Potential of Extracellular Vesicles as Biomarkers and Therapeutic Nanotools for Gastrointestinal Diseases.

Extracellular vesicles (EVs), acting as inherent nanocarriers adept at transporting a range of different biological molecules such as proteins, lipids, and genetic material, exhibit diverse functions within the gastroenteric tract. In states of normal health, they participate in the upkeep of systemic and organ homeostasis. Conversely, in pathological conditions, they significantly contribute to the pathogenesis of gastrointestinal diseases (GIDs). Isolating EVs from patients' biofluids facilitates the discovery of new biomarkers that have the potential to offer a rapid, cost-effective, and non-invasive method for diagnosing and prognosing specific GIDs. Furthermore, EVs demonstrate considerable therapeutic potential as naturally targeted physiological carriers for the intercellular delivery of therapeutic cargo molecules or as nanoscale tools engineered specifically to regulate physio-pathological conditions or disease progression. Their attributes including safety, high permeability, stability, biocompatibility, low immunogenicity, and homing/tropism capabilities contribute to their promising clinical therapeutic applications. This review will delve into various examples of EVs serving as biomarkers or nanocarriers for therapeutic cargo in the context of GIDs, highlighting their clinical potential for both functional and structural gastrointestinal conditions. The versatile and advantageous properties of EVs position them as promising candidates for innovative therapeutic strategies in advancing personalized medicine approaches tailored to the gastroenteric tract, addressing both functional and structural GIDs.

Assembling Near-Infrared Dye on the Surface of Near-Infrared Silica-Coated Copper Sulphide Plasmonic Nanoparticles.

Functionalization of colloidal nanoparticles with organic dyes, which absorb photons in complementary spectral ranges, brings a synergistic effect for harvesting additional light energy. Here, we show functionalization of near-infrared (NIR) plasmonic nanoparticles (NPs) of bare and amino-group functionalized mesoporous silica-coated copper sulphide (Cu2-xS@MSS and Cu2-xS@MSS-NH2) with specific tricarbocyanine NIR dye possessing sulfonate end groups. The role of specific surface chemistry in dye assembling on the surface of NPs is demonstrated, depending on the organic polar liquids or water used as a dispersant solvent. It is shown that dye binding to the NP surfaces occurs with different efficiency, but mostly in the monomer form in polar organic solvents. Conversely, the aqueous medium leads to different scenarios according to the NP surface chemistry. Predominant formation of the disordered dye monomers occurs on the bare surface of mesoporous silica shell (MSS), whereas the amino-group functionalized MSS accepts dye predominantly in the form of dimers. It is found that the dye-NP interaction overcomes the dye-dye interaction, leading to disruption of dye J-aggregates in the presence of the NPs. The different organization of the dye molecules on the surface of silica-coated copper sulphide NPs provides tuning of their specific functional properties, such as hot-band absorption and photoluminescence.

Understanding the Effect of the Synthetic Method and Surface Chemistry on the Properties of CsPbBr3 Nanoparticles.

Over the last decade, the attractive properties of CsPbBr3 nanoparticles (NPs) have driven ever-increasing progress in the development of synthetic procedures to obtain high-quality NPs at high concentrations. Understanding how the properties of NPs are influenced by the composition of the reaction mixture in combination with the specific synthetic methodology is crucial, both for further elucidating the fundamental characteristics of this class of materials and for their manufacturing towards technological applications. This work aims to shed light on this aspect by synthesizing CsPbBr3 NPs by means of two well-assessed synthetic procedures, namely, hot injection (HI) and ligand-assisted reprecipitation (LARP) in non-polar solvents, using PbBr2 and Cs2CO3 as precursors in the presence of already widely investigated ligands. The overall goal is to study and compare the properties of the NPs to understand how each synthetic method influences the NPs' size and/or the optical properties. Reaction composition and conditions are purposely tuned towards the production of nanocubes with narrow size distribution, high emission properties, and the highest achievable concentration. As a result, the formation of bulk crystals as precipitate in LARP limits the achievement of a highly concentrated NP solution. The size of the NPs obtained by LARP seems to be poorly affected by the ligands' nature and the excess bromide, as consequence of bromide-rich solvation agents, effectively results in NPs with excellent emission properties. In contrast, NPs synthesized by HI exhibit high reaction yield, diffusion growth-controlled size, and less striking emission properties, probably ascribed to a bromide-deficient condition.

Synthesis and Characterization of SPIONs Encapsulating Polydopamine Nanoparticles and Their Test for Aqueous Cu2+ Ion Removal.

The removal of pollutants, such as heavy metals, aromatic compounds, dyes, pesticides and pharmaceuticals, from water is still an open challenge. Many methods have been developed and exploited for the purification of water from contaminants, including photocatalytic degradation, biological treatment, adsorption and chemical precipitation. Absorption-based techniques are still considered among the most efficient and commonly used approaches thanks to their operational simplicity. In recent years, polydopamine-coated magnetic nanoparticles have emerged for the uptake of heavy metals in water treatment, since they combine specific affinity towards pollutants and magnetic separation capacity. In this context, this work focuses on the synthesis of polydopamine (PDA)-coated Super Paramagnetic Iron Oxide Nanoparticles (PDA@SPIONs) as adsorbents for Cu2+ ions, designed to serve as functional nanostructures for the removal of Cu2+ from water by applying a magnetic field. The synthetic parameters, including the amount of SPIONs and PDA, were thoroughly investigated to define their effects on the nanostructure features and properties. Subsequently, the ability of the magnetic nanostructures to bind metal ions was assessed on Cu2+-containing solutions. A systematic investigation of the prepared functional nanostructures was carried out by means of complementary spectroscopic, morphological and magnetic techniques. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) measurements were performed in order to estimate the Cu2+ binding ability. The overall results indicate that these nanostructures hold great promise for future bioremediation applications.

The multiple combination of Paclitaxel, Ramucirumab and Elacridar reverses the paclitaxel-mediated resistance in gastric cancer cell lines.

Introduction: Paclitaxel (PTX) interferes with microtubule architecture by binding to ß-tubulin, thereby blocking progression at the G2/M phase and inducing apoptosis. This study aimed to investigate molecular processes underlying PTX-mediated resistance in gastric cancer (GC) cells. Methods: PTX-mediated resistance involves many processes, and in this work some of the factors involved in the resistance mechanism were identified by comparing two GC lines with PTX induced resistance to their sensitive counterparts. Results: Thus, the key feature of PTX-resistant cells was the overexpression of pro-angiogenic factors such as VEGFA, VEGFC, and Ang2, known to support tumor cell growth. A second relevant change detected in PTX-resistant lines was the elevated level of TUBßIII, a tubulin isoform that opposes microtubule stabilization. A third identified factor contributing to PTX-resistance was P-glycoprotein (P-gp), a transporter responsible for chemotherapy efflux from the cells, highly expressed in PTX-resistant lines. Discussion: These findings were in line with a greater sensitivity of resistant cells to treatment with both Ramucirumab and Elacridar. Ramucirumab significantly reduced the expression of angiogenic molecules and TUBßIII, while Elacridar restored the access of chemotherapy, recovering its anti-mitotic and pro-apoptotic effects. Finally, this study highlighted the role played by exosomes in spreading factors responsible for resistance in the tumor microenvironment.