Iron chelates in the anticancer therapy

Iron plays a significant role in the metabolism of cancer cells. In comparison with normal cells, neoplastic ones exhibit enhanced vulnerability to iron. Ferric ions target tumor via the ferroptotic death pathway—a process involving the iron-mediated lipid oxidation. Ferric ion occurs in complex forms in the physiological conditions. Apart from iron, ligands are the other factors to affect the biological activity of the iron complexes. In recent decades the role of iron chelates in targeting the growth of the tumor was extensively examined. The ligand may possess a standalone activity to restrict cancer’s growth. However, a wrong choice of the ligand might lead to the enhanced cancer cell’s growth in in vitro studies. The paper aims to review the role of iron complex compounds in the anticancer therapy both in the experimental and clinical applications. The anticancer properties of the iron complex rely both on the stability constant of the complex and the ligand composition. When the stability constant is high, the properties of the drug are unique. However, when the stability constant remains low, both components—ferric ions and ligands, act separately on the cells. In the paper we show how the difference in complex stability implies the action of ligand and ferric ions in the cancer cell. Iron complexation strategy is an interesting attempt to transport the anticancer Fe2+/3+ ions throughout the cell membrane and release it when the pH of the microenvironment changes. Last part of the paper summarizes the results of clinical trials and in vitro studies of novel iron chelates such as: PRLX 93,936, Ferumoxytol, Talactoferrin, DPC, Triapine, VLX600, Tachypyridine, Ciclopiroxamine, Thiosemicarbazone, Deferoxamine and Deferasirox.

Liquid-Liquid Extraction of Ferric Ions into the Ionic Liquids

Imidazolium ionic liquids containing acetylacetone, thenoyltrifluoroacetone, or 8-hydroxyquinoline, respectively, were used as the extracting agents for the separation of traces of iron (III) from its aqueous solutions with or without citric and oxalic acids. The results show that 8-hydroxyquinoline in imidazolium ionic liquids extract iron quantitatively from all the tested solutions including complexing ones, regardless of indications of unexpected iron behavior/speciation.

Iron-Utilization System in Vibrio vulnificus M2799

Vibrio vulnificus is a Gram-negative pathogenic bacterium that causes serious infections in humans and requires iron for growth. A clinical isolate, V. vulnificus M2799, secretes a catecholate siderophore, vulnibactin, that captures ferric ions from the environment. In the ferric-utilization system in V. vulnificus M2799, an isochorismate synthase (ICS) and an outer membrane receptor, VuuA, are required under low-iron conditions, but alternative proteins FatB and VuuB can function as a periplasmic-binding protein and a ferric-chelate reductase, respectively. The vulnibactin-export system is assembled from TolCV1 and several RND proteins, including VV1_1681. In heme acquisition, HupA and HvtA serve as specific outer membrane receptors and HupB is a sole periplasmic-binding protein, unlike FatB in the ferric-vulnibactin utilization system. We propose that ferric-siderophore periplasmic-binding proteins and ferric-chelate reductases are potential targets for drug discovery in infectious diseases.

Myricetin-Based Self-Assembled Nanoparticles for Tumor Synergistic Therapy by Antioxidation Pathway

Nanoplatforms are nano-scale systems that can transport different small molecular anticancer drugs or chemosensitization motif to accumulate in tumor cells without obvious side-effect in normal cells and achieve a synergistic therapy. In this paper the new self-assembled nanoparticles (NPs) merging doxorubicin (DOX) and myricetin (MYR) with ferric ions (Fe3+) and polyphenol was employed for forming the DOX@MYR-Fe3+ NP (FDMP NP). The FDMP NPs could reduce the DOX-induced toxicity in blood; and they could not cause damage to the heart and kidney tissues by the reasons that the MYR could enhance the anti-oxidation capability in normal cells, which resulted in preventing ROS-induced damage. Additionally, the FDMP NPs were characteristic of small size (37.70 ± 6.30 nm), high DOX loading efficiency (46.67 ± 1.58%), pH-controlled release and excellent stable pharmacokinetics, that inducing drug release and enhancing drug accumulation in the tumor. Moreover, the FDMP NPs could inhibit the expression of the hypoxia-inducible factor-1 α(HIF-1α) and the key angiogenesis mediator vascular endothelial growth factor (VEGF) both in vitro and in vivo, which succeed in preventing the generation of new blood vessel networks; that is the mechanism of the synergistic effect against tumors induced by FDMP NPs.

Liquid-Liquid Extraction of Ferric Ions Into the Ionic Liquids

(200 words) Imidazolium ionic liquids containing acetylacetone, thenoyltrifluoroacetone, or 8-hydroxyquinoline, respectively, were used as the extracting agents for the separation of traces of iron (III) from its aqueous solutions with or without citric and oxalic acids. The results show that 8-hydroxyquinoline in imidazolium ionic liquids extract iron quantitatively from all the tested solutions including complexing ones, regardless indications of unexpected iron behavior/speciation.

Regulation and Functional Complexity of the Chlorophyll-Binding Protein IsiA

As the oldest known lineage of oxygen-releasing photosynthetic organisms, cyanobacteria play the key roles in helping shaping the ecology of Earth. Iron is an ideal transition metal for redox reactions in biological systems. Cyanobacteria frequently encounter iron deficiency due to the environmental oxidation of ferrous ions to ferric ions, which are highly insoluble at physiological pH. A series of responses, including architectural changes to the photosynthetic membranes, allow cyanobacteria to withstand this condition and maintain photosynthesis. Iron-stress-induced protein A (IsiA) is homologous to the cyanobacterial chlorophyll (Chl)-binding protein, photosystem II core antenna protein CP43. IsiA is the major Chl-containing protein in iron-starved cyanobacteria, binding up to 50% of the Chl in these cells, and this Chl can be released from IsiA for the reconstruction of photosystems during the recovery from iron limitation. The pigment–protein complex (CPVI-4) encoded by isiA was identified and found to be expressed under iron-deficient conditions nearly 30years ago. However, its precise function is unknown, partially due to its complex regulation; isiA expression is induced by various types of stresses and abnormal physiological states besides iron deficiency. Furthermore, IsiA forms a range of complexes that perform different functions. In this article, we describe progress in understanding the regulation and functions of IsiA based on laboratory research using model cyanobacteria.

Construction of a Luminescent Cadmium-Based Metal–Organic Framework for Highly Selective Discrimination of Ferric Ions

Fluorescent metal–organic frameworks (MOFs) are ideal materials for sensors because of their adjustable pore size and functional groups, which provide them with favorable metal ion selective recognition. In this paper, a new cadmium-based MOF was synthesized using Cd(NO3)2·4H2O and 3,3′,5,5′-biphenyltetracarboxylic acid by solvothermal method. CdBPTC owned three types of channels with dimensions of approximately 8.4 × 8.3 Å, 6.0 × 5.2 Å, 9.7 × 8.4 Å along a, b, and c axis, respectively. This MOF has high selectivity to ferric ions and shows excellent anti-inference ability toward many other cations. The results indicate that the fluorescence quenching efficiency of CdBPTC is close to 100% when the concentration of Fe3+ reaches 1.0 × 10−3 mol·L−1. Moreover, the luminescent intensity at 427 nm presents a linear relationship at a concentration range of 2.0 × 10−4~7.0 × 10−4 mol·L−1, which can be quantitatively expressed by the linear Stern–Volmer equation I0/I = 8489 [Fe3+] − 0.1400, which is comparable to the previously reported better-performing materials. Competitive energy absorption and ion exchange may be responsible for the variation in fluorescence intensity of CdBPTC in different Fe3+ concentrations.