Time-Resolved Dynamics of Laser Ablation in Liquid with Gas-Evolving Additives: Toward Molding the Atomic Structure of Nonequilibrium Nanoalloys.

Laser ablation in liquid (LAL) is a reference technique for the synthesis of multicomponent non-equilibrium nanomaterials which have potentially disruptive properties in photonics, nanomedicine, and catalysis. Yet, ablation dynamics is poorly understood regarding the multielement matter and, therefore, the remarkable potential of LAL for controlling the local atomic structure of metastable nanophases remains largely unexploited. Here, the dynamics of LAL are investigated with non-equilibrium gold-iron nanoalloys generated in the presence of gas-evolving additives, which drive the formation of different nanostructures.

Rhodium nanospheres for ultraviolet and visible plasmonics.

The development and understanding of alternative plasmonic materials are crucial steps for leveraging new plasmonic technologies. Although gold and silver nanostructures have been intensively studied, the promising plasmonic, chemical and physical attributes of rhodium remain poorly investigated. Here, we report the synthesis and plasmonic response of spherical Rh nanoparticles (NPs) with sizes in the 20-40 nm range.

Surface Gold Atoms Determine Peroxidase Mimic Activity in Gold Alloy Nanoparticles.

The development of peroxidase mimic nanocatalysts is relevant for oxidation reactions in biosensing, environmental monitoring and green chemical processes. Several nanomaterials have been proposed as peroxidase mimic, the majority of which consists of noble metals and oxide nanoparticles (NPs). Yet, there is still limited information about how the change in the composition influences their catalytic activity.

Physical and chemical parameters determining the formation of gold-sp metal (Al, Ga, In, and Pb) nanoalloys.

Alloying is a key step towards the fabrication of advanced and unique nanomaterials demanded by the next generation of nanotechnology solutions. In particular, the alloys of Au with the sp-metals are expected to have several appealing plasmonic and electronic properties for a wide range of applications in optics, catalysis, nanomedicine, sensing and quantum devices. However, little is known about the thermodynamic and synthetic factors leading to the successful alloying of Au and sp-metals at the nanoscale.

Accurate prediction of the optical properties of nanoalloys with both plasmonic and magnetic elements.

The alloying process plays a pivotal role in the development of advanced multifunctional plasmonic materials within the realm of modern nanotechnology. However, accurate in silico predictions are only available for metal clusters of just a few nanometers, while the support of modelling is required to navigate the broad landscape of components, structures and stoichiometry of plasmonic nanoalloys regardless of their size. Here we report on the accurate calculation and conceptual understanding of the optical properties of metastable alloys of both plasmonic (Au) and magnetic (Co) elements obtained through a tailored laser synthesis procedure.

Recent Developments in Plasmonic Alloy Nanoparticles: Synthesis, Modelling, Properties and Applications.

Despite the traditional plasmonic materials are counted on one hand, there are a lot of possible combinations leading to alloys with other elements of the periodic table, in particular those renowned for magnetic or catalytic properties. It is not a surprise, therefore, that nanoalloys are considered for their ability to open new perspectives in the panorama of plasmonics, representing a leading research sector nowadays. This is demonstrated by a long list of studies describing multiple applications of nanoalloys in photonics, photocatalysis, sensing and magneto-optics, where plasmons are combined with other physical and chemical phenomena.

Preclinical Development of FA5, a Novel AMP-Activated Protein Kinase (AMPK) Activator as an Innovative Drug for the Management of Bowel Inflammation.

Acadesine (ACA), a pharmacological activator of AMP-activated protein kinase (AMPK), showed a promising beneficial effect in a mouse model of colitis, indicating this drug as an alternative tool to manage IBDs. However, ACA displays some pharmacodynamic limitations precluding its therapeutical applications. Our study was aimed at evaluating the in vitro and in vivo effects of FA-5 (a novel direct AMPK activator synthesized in our laboratories) in an experimental model of colitis in rats.

Identification of ALDH1A3 as a Viable Therapeutic Target in Breast Cancer Metastasis-Initiating Cells.

The development of efficacious therapies targeting metastatic spread of breast cancer to the brain represents an unmet clinical need. Accordingly, an improved understanding of the molecular underpinnings of central nervous system spread and progression of breast cancer brain metastases (BCBM) is required. In this study, the clinical burden of disease in BCBM was investigated, as well as the role of aldehyde dehydrogenase 1A3 (ALDH1A3) in the metastatic cascade leading to BCBM development.

Dual Kit/Aur Inhibitors as Chemosensitizing Agents for the Treatment of Melanoma: Design, Synthesis, Docking Studies and Functional Investigation.

Melanoma is the most serious form of skin cancer but its medication is still far from being safe and thoroughly effective. The search of novel therapeutic approaches represents therefore a health emergency to push through eagerly. In this study, we describe a novel class of dual c-Kit/Aur inhibitors, characterized by a 1,2,4-triazole core and developed by a structure-based optimization of a previously developed hit, and report the evidence of their significance as drug candidates for the treatment of melanoma.

Acid Derivatives of Pyrazolo[1,5-a]pyrimidine as Aldose Reductase Differential Inhibitors.

Aldose reductase (AKR1B1), the key enzyme of the polyol pathway, plays a crucial role in the development of long-term complications affecting diabetic patients. Nevertheless, the expedience of inhibiting this enzyme to treat diabetic complications has failed, due to the emergence of side effects from compounds under development. Actually AKR1B1 is a Janus-faced enzyme which, besides ruling the polyol pathway, takes part in the antioxidant defense mechanism of the body.

Challenging clinically unresponsive medullary thyroid cancer: Discovery and pharmacological activity of novel RET inhibitors.

It is now known that "gain of function" mutations of RET (REarranged during Transfection) kinase are specific and key oncogenic events in the onset of thyroid gland cancers such as the Medullary Thyroid Carcinoma (MTC). Although a number of RET inhibitors exist and are capable of inhibiting RET variants, in which mutations are outside the enzyme active site, the majority becomes dramatically ineffective when mutations are within the protein active site (V804L and V804M). Pursuing a receptor-based virtual screening against the kinase domain of RET, we found that compound 5 is able to inhibit efficiently both wild type and V804L mutant RET.

Novel quinazolinone-based 2,4-thiazolidinedione-3-acetic acid derivatives as potent aldose reductase inhibitors.

Aim: Targeting aldose reductase enzyme with 2,4-thiazolidinedione-3-acetic acid derivatives having a bulky hydrophobic 3-arylquinazolinone residue.

Materials & Methods: All the target compounds were structurally characterized by different spectroscopic methods and microanalysis, their aldose reductase inhibitory activities were evaluated, and binding modes were studied by molecular modeling.

Results: All the synthesized compounds proved to inhibit the target enzyme potently, exhibiting IC values in the nanomolar/low nanomolar range.

Quinazolinone-based rhodanine-3-acetic acids as potent aldose reductase inhibitors: Synthesis, functional evaluation and molecular modeling study.

A series of quinazolinone-based rhodanine-3-acetic acids was synthesized and tested for in vitro aldose reductase inhibitory activity. All the target compounds displayed nanomolar activity against the target enzyme. Compounds 3a, 3b, and 3e exhibited almost 3-fold higher activity as compared to the only marketed reference drug epalrestat.

Synthesis and Functional Evaluation of Novel Aldose Reductase Inhibitors Bearing a Spirobenzopyran Scaffold.

Background: Aldose reductase, the first enzyme of the polyol pathway, is the key determinant for the pathogenesis of long term diabetic complications. Accordingly, its inhibition represents the major therapeutic strategy to treat this kind of pathologies.

Objectives: In this work we describe the synthesis and the functional evaluation of a number of spiro-oxazolidinone and spiro-morpholinone acetic acid derivatives, and their benzyloxy analogs, developed as aldose reductase inhibitors.

Cyclodextrin-based nanosponges for the targeted delivery of the anti-restenotic agent DB103: A novel opportunity for the local therapy of vessels wall subjected to percutaneous intervention.

Nano-sized colloidal carriers represent innovative drug delivery systems, as they allow a targeted and prolonged release of poorly water-soluble drugs, improving their bioavailability and modifying their pharmacokinetic parameters. In this work we describe cyclodextrin-based nanosponges, obtained through polimerization of β-cyclodextrin with diphenyl carbonate as the cross-linking agent, loaded with a novel multi-effective heterocyclic compound, DB103, able to regulate key cellular events involved in the remodelling of vessels wall. Fabrication and drug-loading procedures, as well as physical-chemical characterization and drug-release profile of the novel colloidal system are reported.

FOXD1-ALDH1A3 Signaling Is a Determinant for the Self-Renewal and Tumorigenicity of Mesenchymal Glioma Stem Cells.

Glioma stem-like cells (GSC) with tumor-initiating activity orchestrate the cellular hierarchy in glioblastoma and engender therapeutic resistance. Recent work has divided GSC into two subtypes with a mesenchymal (MES) GSC population as the more malignant subtype. In this study, we identify the FOXD1-ALDH1A3 signaling axis as a determinant of the MES GSC phenotype.

1,2-Benzisothiazole Derivatives Bearing 4-, 5-, or 6-Alkyl/arylcarboxamide Moieties Inhibit Carbonic Anhydrase Isoform IX (CAIX) and Cell Proliferation under Hypoxic Conditions.

Three novel series of 1,2-benzisothiazole derivatives have been developed as inhibitors of carbonic anhydrase isoform IX. Compounds 5c and 5j, tested in vitro on the human colon cell line HT-29, blocked the growth of cells cultured under chemically induced hypoxic conditions, displaying a specific activity against cancer cells characterized by CAIX up-regulation. Moreover, a synergistic activity of 5c with SN-38 (the active metabolite of irinotecan) and 5-fluorouracil on cell proliferation under hypoxic conditions was demonstrated.

Nanostructured ultra-thin patches for ultrasound-modulated delivery of anti-restenotic drug.

This work aims to demonstrate the possibility to fabricate ultra-thin polymeric films loaded with an anti-restenotic drug and capable of tunable drug release kinetics for the local treatment of restenosis. Vascular nanopatches are composed of a poly(lactic acid) supporting membrane (thickness: ~250 nm) on which 20 polyelectrolyte bilayers (overall thickness: ~70 nm) are alternatively deposited. The anti-restenotic drug is embedded in the middle of the polyelectrolyte structure, and released by diffusion mechanisms.

Structure-based optimization of tyrosine kinase inhibitor CLM3. Design, synthesis, functional evaluation, and molecular modeling studies.

Recent advances in the knowledge of thyroid carcinomas development identified receptor tyrosine kinases, like VEGFR2 and RET, as viable and promising targets. Accordingly, their inhibition is emerging as the major therapeutic strategy to treat these pathologies. In this study we describe the synthesis and the functional evaluation of three different series of 4-substituted pyrazolo[3,4-d]pyrimidine derivatives, 8a-g, 9a-g, and 10a-g, designed exploiting a structure-based optimization of the previously developed inhibitor CLM3.