Iole Venditti

The aim of this work is to evaluate different nanostructured systems based on noble metal nanoparticles suitable for drug delivery and release related to the treatment of multiple sclerosis. To this end, four different systems are thoroughly characterized from a chemical-physical and structural perspective and, then, from a biological perspective. Gold and silver nanoparticles were synthesized and stabilized with different biocompatible ligands, including poly(ethylene glycol), citrate, and cysteine, to modulate their colloidal stability and surface reactivity. UV–Vis spectroscopy revealed characteristic plasmonic absorption bands at about 400 nm for silver and nearly 550 nm for gold nanoparticles. Morphological analyses, performed by Transmission Electron Microscopy, and colloidal stability, studied by Dynamic Light Scattering, highlighted differences in size distribution and polydispersity among the systems. The nanoparticles were subsequently functionalized with fluorescein isothiocyanate, a fluorescent dye, to enable their detection and tracking within cells using an accessible analytical technique appropriate for the study of immune cells, such as flow cytometry. Nanoparticle surface properties were thoroughly investigated by means of Fourier-transform infrared, synchrotron radiation-induced X-ray photoelectron, and near edge X-ray absorption fine structure spectroscopies. Flow cytometry analyses demonstrated efficient nanoparticle–cell interaction with peripheral blood mononuclear cells, and a cell viability assay performed with the improved system highlighted the potential for applications in drug delivery and bioimaging.

Hospital wastewater has begun to act as an important source of emerging contaminants, including rare earth elements (REEs), mostly lanthanides, and radiopharmaceutical residues originating from diagnostic and therapeutic nuclear medicine procedures. The increasing use of gadolinium-based contrast agents, lutetium-containing therapeutics, technetium-99m tracers, iodine-131, yttrium-90, and gallium-68 radiopharmaceuticals has raised growing concerns regarding the release of radioactive and metal-containing compounds into aquatic environments. Conventional wastewater treatment plants are often inefficient in removing these contaminants because of their high chemical stability, low environmental concentrations, and complex aqueous speciation. In this context, hybrid nanomaterials containing silver nanoparticles (AgNPs) have attracted increasing interest for both monitoring and remediation applications. AgNP-based systems exhibit unique plasmonic, catalytic, antimicrobial, and sensing properties that can be exploited in adsorption, photocatalysis, membrane filtration, electrochemical detection, and surface-enhanced Raman spectroscopy (SERS). This review critically analyzes recent advances in hospital wastewater treatment and how hybrid nanomaterials containing silver nanoparticles (AgNPs) are emerging. The review places a particular focus on contamination by REEs and radiopharmaceuticals residues, which to date, as far as we know, remains a challenging and understudied aspect, as reflected by limited publications.

The creation of innovative systems that are able to combine diagnosis and therapy is a crucial opportunity in nuclear medicine. Here, we propose a methodological and multiscale approach for the development of a theranostic platform based on AuNRs functionalized with radiopharmaceuticals. AuNRs offer a versatile and effective system due to their unique physicochemical properties and the possibility of surface functionalization with targeting molecules. Within this framework, key challenges include the functionalization of AuNRs to target the cell nucleus, the loading of AuNRs with radiopharmaceuticals, and the investigation of Auger electron emission from AuNRs under gamma irradiation. Multiscale modelling is employed to describe the behaviour of the system within the cellular environment and to predict potential radiobiological enhancement effects, including synergistic interactions between functionalized AuNRs and radiopharmaceutical agents such as ^99mTc-sestaMIBI. The experimental activity includes gamma irradiation studies, along with the structural and physical characterization of nanomaterials and in vitro biological investigations on T98G cells, to evaluate cytotoxicity and metabolic alterations, with the aim of assessing the potential synergistic effects of the combined system.

Bis­(pyrazol-1-yl)­acetic acid (HC­(pz)₂COOH) and bis­(3,5-dimethyl-pyrazol-1-yl)­acetic acid (HC­(pz^Me2)₂COOH) were conjugated with amantadine to yield the ligands L^Ad and L^2Ad, respectively. These chelating ligands were used for the synthesis of silver complexes 1–5, whose electronic and molecular structures were investigated by X-ray Photoelectron Spectroscopy (XPS) and Near Edge X-ray Absorption Fine Structure (NEXAFS) spectroscopy. The coordination geometry of the noble metal ion was assessed by combining X-ray Absorption Spectroscopy (XAS) data analysis with Density Functional Theory (DFT) modeling. The structures of the ligand L^Ad and of the complex [Ag­(L^2Ad)­(PPh₃)]­NO₃·0.5CH₃CN (3a) were determined by single-crystal X-ray diffraction analysis. The bis­(pyrazolyl)­acetamide ligand crystallizes in the I2/a space group and is similar to the 3,5-dimethyl analogue. The complex crystallizes in the P-1 space group and is the first reported example of a tetra-coordinated silver­(I) complex incorporating a tridentate bis­(pyrazolyl)­acetate ligand. The cytotoxicity potential of the new phosphane Ag­(I) complexes was tested on various human cancer cell lines, together with that of the two unfunctionalized analogs [Ag­(L^2OiPr)­(PPh₃)]­NO₃ (6) and [Ag­(L^2OiPr)­(PTA)]­NO₃ (7), synthesized and studied for useful comparison. Notably, the novel complexes exhibited pronounced cytotoxic effects against the human-derived pancreatic cancer BxPC-3 cell line, both in 2D monolayers and in 3D spheroid models. Mechanistic studies revealed efficient intracellular accumulation of the complexes, likely favored by increased lipophilicity, and inhibition of thioredoxin reductase (TrxR), ultimately disrupting redox homeostasis and promoting oxidative stress, which are key contributors to their antiproliferative effects.

Metal-based and polymeric nanoparticles acquire unique protein corona in the coelomic fluid of sea urchin Paracentrotus lividus , linking molecular fingerprints to in vitro biological responses.

Gold nanoparticles are proving to be highly successful for delivering drugs to specific targets, exploiting carefully designed functionalizations. This work creates and optimizes the synthesis of gold nanorods (AuNRs), subsequently functionalized with a peptide, TAT, appropriately modified to allow attachment to the rods and guide their entry into the cell nucleus and nuclear growth. Various chemical and physical characterizations were performed to verify and optimize the AuNRs-TAT system. DLS, Z-potential, UV–vis, and FT-IR spectroscopies confirmed the nanosize, monodispersity, colloidal stability, and successful functionalization. Furthermore, structural characterizations conducted using synchrotron radiation were crucial for understanding the actual interaction between the gold surface and the modified TAT peptide. The study highlighted how this material is indeed a good drug delivery system, stable over time, and promising for reaching the cell nucleus.

Gold nanorods (AuNRs) were synthesized and optimized with the aim of obtaining strongly hydrophilic nanomaterials, suitable as a drug delivery system (DDS) for copper-based drugs. After careful purification, AuNRs were characterized by ultraviolet–visible–near-infrared spectroscopy (UV–Vis–NIR), showing two typical localized surface plasmon resonance (LSPR) bands in the range 550–750 nm. Fourier Transform Infrared (FT-IR) and high-resolution X-ray photoelectron (HR-XPS) spectroscopies verified the surface functionalization. Transmission electron microscopy (TEM) showed AuNRs with regular shape and size, with an aspect ratio (AR) of 2.6. Dynamic Light Scattering (DLS) measurements confirmed the size and the stability in water for up to 3 months. The AuNRs were conjugated with copper(I) drugs, i.e., [Cu(PTA)₄]BF₄ (PTA = 1,3,5-triaza-7-phosphadamantane). The drug loading procedures and efficiency were optimized, and the best loading was η (%) = 50 ± 7%. The non-covalent interactions of the Cu(I) complex with the AuNRs were studied by means of UV–Vis–NIR, ζ-potential, HR-TEM, FT-IR, synchrotron radiation-induced X-ray photoelectron (SR-XPS), and near-edge X-ray absorption fine structure (NEXAFS) spectroscopy measurements. The MTT assay performed on Vero E6 cells showed that AuNRs and AuNR-Cu(I) conjugates had no significant effect on cell viability, being biocompatible, causing a reduction in cell viability only after prolonged exposure.

This paper reports the synthesis, structural characterization, and biological evaluation of a novel series of Cu^I and Cu^II complexes supported by an amantadine-functionalized bis(pyrazol-1-yl)acetate ligand (L^Ad) as potential anticancer agents for the treatment of glioblastoma (GBM). Comprehensive spectroscopic and structural investigations, including SR-XPS, XANES/EXAFS, and DFT modeling, confirmed the successful coordination of L^Ad to copper centers in both oxidation states, affording well-defined molecular architectures with distinct coordination geometries. Among the synthesized compounds, the Cu^I complexes bearing triphenylphosphine co-ligands (compounds 4 and 5) exhibited the strongest cytotoxicity against U87 MG and LN18 GBM cell lines, showing IC₅₀ values lower than those of cisplatin. These complexes induced a pronounced redox imbalance through reactive oxygen species (ROS) overproduction and glutathione (GSH) depletion, leading to G2/M cell cycle arrest and cell death. Flow cytometry and Western blot analyses demonstrated that cell death occurs via caspase-dependent apoptosis in LN18 cells, as evidenced by PARP cleavage, downregulation of Bcl-xL, release of cytochrome c, and mitochondrial translocation of Bax. Altogether, these findings highlight the potential of lipophilic amantadine-functionalized Cu^I complexes as promising anticancer candidates targeting glioma cells through mitochondrial dysfunction and redox-mediated pathways.

The aim of this research was to assess the sex-related responses to AgNPs stabilized with citrate (Cit) and glutathione (GSH), relative to silver ions supplied as AgNO₃ in black poplar (Populus nigra L.), a dioecious, woody model species. The impact of the AgNPs-cit-GSH on male and female clones was evaluated by measuring key parameters of oxidative stress. The results showed that exposure to nanosilver resulted in lower Ag accumulation and reduced MDA levels in both genders compared to AgNO₃. The female clone exhibited a dose-dependent response, characterized by an increase in dry weight (DW), along with a reduction in nutrient uptake, protein content, and ATPase activity, as well as an upregulation of glutathione-S-transferase (GST) activity compared to the control. The male clone displayed a specific treatment response. Exposure to AgNPs-cit-GSH caused a decrease in DW, water content, and nutrient uptake, accompanied by a rise in protein content as well as GST activity. In AgNO₃-treated male cells, the increase in Ag content and MDA levels corresponded to a decrease in DW and a rise in protein, Cu, and Ca content. These findings offer valuable insights into sexual dimorphism in dioecious woody plants, a topic that has been largely understudied yet is critical for sustainable resource management strategies.