In the human body, copper (Cu) is a major and essential player in a large number of cellular mechanisms and signaling pathways. The involvement of Cu in oxidation–reduction reactions requires close regulation of copper metabolism in order to avoid toxic effects. In many types of cancer, variations in copper protein levels have been demonstrated. These variations result in increased concentrations of intratumoral Cu and alterations in the systemic distribution of copper. Such alterations in Cu homeostasis may promote tumor growth or invasiveness or may even confer resistance to treatments. Once characterized, the dysregulated Cu metabolism is pinpointing several promising biomarkers for clinical use with prognostic or predictive capabilities. The altered Cu metabolism in cancer cells and the different responses of tumor cells to Cu are strongly supporting the development of treatments to disrupt, deplete, or increase Cu levels in tumors. The metallic nature of Cu as a chemical element is key for the development of anticancer agents via the synthesis of nanoparticles or copper-based complexes with antineoplastic properties for therapy. Finally, some of these new therapeutic strategies such as chelators or ionophores have shown promising results in a preclinical setting, and others are already in the clinic.

The present work was focused on the synthesis and characterization of hydroxyapatite doped with low concentrations of zinc (Zn:HAp) (0.01 < x_Zn < 0.05). The incorporation of low concentrations of Zn²⁺ ions in the hydroxyapatite (HAp) structure was achieved by co-precipitation method. The physico-chemical properties of the samples were characterized by X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Scanning Electron Microscopy (SEM), zeta-potential, and DLS and N₂-BET measurements. The results obtained by XRD and FTIR studies demonstrated that doping hydroxyapatite with low concentrations of zinc leads to the formation of a hexagonal structure with lattice parameters characteristic to hydroxyapatite. The XRD studies have also shown that the crystallite size and lattice parameters of the unit cell depend on the substitutions of Ca²⁺ with Zn²⁺ in the apatitic structure. Moreover, the FTIR analysis revealed that the water content increases with the increase of zinc concentration. Furthermore, the Energy Dispersive X-ray Analysis (EDAX) and XPS analyses showed that the elements Ca, P, O, and Zn were found in all the Zn:HAp samples suggesting that the synthesized materials were zinc doped hydroxyapatite, Ca_10−xZn_x(PO₄)₆(OH), with 0.01 ≤ x_Zn ≤ 0.05. Antimicrobial assays on Staphylococcus aureus and Escherichia coli bacterial strains and HepG2 cell viability assay were carried out.

Silver nanoparticles (AgNPs) can enter eukaryotic cells and exert toxic effects, most probably as a consequence of the release of Ag⁺ ions. Due to the elusive nature of Ag⁺ ionic species, quantitative information concerning AgNP intracellular dissolution is missing. By using a synchrotron nanoprobe, silver is visualized and quantified in hepatocytes (HepG2) exposed to AgNPs; the synergistic use of electron microscopy allows for the discrimination between nanoparticular and ionic forms of silver within a single cell. AgNPs are located in endocytosis vesicles, while the visualized Ag⁺ ions diffuse in the cell. The averaged NP dissolution rates, measured by X-ray absorption spectroscopy, highlight the faster dissolution of citrate-coated AgNPs with respect to the less toxic PVP-coated AgNPs; these results are confirmed at the single-cell level. The released Ag⁺ ions recombine with thiol-bearing biomolecules: the Ag–S distances measured in cellulo, and the quantitative evaluation of gene expression, provide independent evidence of the involvement of glutathione and metallothioneins in Ag⁺ binding. The combined use of cutting-edge imaging techniques, atomic spectroscopy and molecular biology brings insight into the fate of AgNPs in hepatocytes, and more generally into the physicochemical transformations of metallic nanoparticles in biological environments and the resulting disruption of metal homeostasis.

The aim of the current research work was to study the physicochemical and biological properties of synthesized zinc doped hydroxyapatite (ZnHAp) nanoparticles with Zn concentrationsxZn=0(HAp),xZn=0.07(7ZnHAp), andxZn=0.1(10ZnHAp) for potential use in biological applications. The morphology, size, compositions, and incorporation of zinc into hydroxyapatite were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), Raman scattering, and X-Ray Photoelectron Spectroscopy (XPS). In addition, the cytotoxicity of ZnHAp nanoparticles was tested on bothE. colibacteria and human hepatocarcinoma cell line HepG2. The results showed that ZnHAp nanoparticles (HAp, 7ZnHAp, and 10ZnHAp) have slightly elongated morphologies with average diameters between 25 nm and 18 nm. On the other hand, a uniform and homogeneous distribution of the constituent elements (calcium, phosphorus, zinc, and oxygen) in the ZnHAp powder was noticed. Besides, FTIR and Raman analyses confirmed the proper hydroxyapatite structure of the synthesized ZnHAp nanoparticles with the signature of phosphate, carbonate, and hydroxyl groups. Moreover, it can be concluded that Zn doping at the tested concentrations is not inducing a specific prokaryote or eukaryote toxicity in HAp compounds.

Iron (Fe) is a trace element that plays essential roles in various biological processes such as DNA synthesis and repair, as well as cellular energy production and oxygen transport, and it is currently widely recognized that iron homeostasis is dysregulated in many cancers. Indeed, several iron homeostasis proteins may be responsible for malignant tumor initiation, proliferation, and for the metastatic spread of tumors. A large number of studies demonstrated the potential clinical value of utilizing these deregulated proteins as prognostic and/or predictive biomarkers of malignancy and/or response to anticancer treatments. Additionally, the iron present in cancer cells and the importance of iron in ferroptosis cell death signaling pathways prompted the development of therapeutic strategies against advanced stage or resistant cancers. In this review, we select relevant and promising studies in the field of iron metabolism in cancer research and clinical oncology. Besides this, we discuss some co-existing discrepant findings. We also present and discuss the latest lines of research related to targeting iron, or its regulatory pathways, as potential promising anticancer strategies for human therapy. Iron chelators, such as deferoxamine or iron-oxide-based nanoparticles, which are already tested in clinical trials, alone or in combination with chemotherapy, are also reported.