Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity

Abstract

The great advances in the studies on metal complexes for the treatment of different cancer forms, starting from the pioneering works on platinum derivatives, have fostered an increasingly growing interest in their properties and biomedical applications. Among the various metal-containing drugs investigated thus far, ruthenium(III) complexes have emerged for their selective cytotoxic activity in vitro and promising anticancer properties in vivo, also leading to a few candidates in advanced clinical trials. Aiming at addressing the solubility, stability and cellular uptake issues of low molecular weight Ru(III)-based compounds, some research groups have proposed the development of suitable drug delivery systems (e.g., taking advantage of nanoparticles, liposomes, etc.) able to enhance their activity compared to the naked drugs. This review highlights the unique role of Ru(III) complexes in the current panorama of anticancer agents, with particular emphasis on Ru-containing nanoformulations based on the incorporation of the Ru(III) complexes into suitable nanocarriers in order to enhance their bioavailability and pharmacokinetic properties. Preclinical evaluation of these nanoaggregates is discussed with a special focus on the investigation of their mechanism of action at a molecular level, highlighting their pharmacological potential in tumour disease models and value for biomedical applications.

Synthesis, Antiproliferative Activity, and DNA Binding Studies of Nucleoamino Acid-Containing Pt(II) Complexes

“…Their interaction in solution was investigated with four DNA model systems, i.e., a random coil single strand, two B form-duplexes, one with and the other without a GG box, and a G-quadruplex structure. From CD binding experiments, it emerged that DNA can be a possible target of these brand new compounds, similar to other reported bioactive Pt complexes (as well as transition metal complexes, such as ruthenium complexes) [ 6 , 7 , 12 , 15 , 21 , 23 , 47 , 48 , 52 , 53 ]. In particular, we observed significant changes only in the CD spectrum of the single strand and G4 when T1 and T2 were added to each DNA system, evidencing that both the complexes interacted with these oligonucleotides.…”

Breast Cancer Chemotherapeutic Options: A General Overview on the Preclinical Validation of a Multi-Target Ruthenium(III) Complex Lodged in Nucleolipid Nanosystems

“…Ruthenium compounds exist in three main oxidation states. While Ru(IV) compounds are unstable, Ru(III) complexes have a good thermodynamic and kinetic stability, and can be used as prodrugs, showing antitumor effect by reduction in situ to corresponding Ru(II) counterparts under biological conditions of decreased pH, hypoxia, and increased levels of glutathione, as described later [87,88]. Conversely, Ru(II) can directly inhibit cancer cells via multiple mechanisms, some of which are yet to be elucidated.…”

“…To exploit the advantages of nanotechnology, very recently many ruthenium compounds have been successfully converted into nanomaterials [87,90,91,[129][130][131]. Due to both their passive and active tumor targeting properties, diverse nanostructured materials could hire a central role in cancer therapeutics.…”

Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems

“…Li et al have also functionalized the carbon quantum dots so that they structurally mimic large amino acids that can selectively accumulate at tumor sites for both imaging and drug delivery purposes [149]. A recent review by Riccardi et al summarizes the development of different nanocarriers with various decorations (or functionalization) for the improvement in bioavailability, pharmacokinetics, and specificity of anticancer ruthenium-based drugs [150].…”