Emerging Molecular Receptors for the Specific-Target Delivery of Ruthenium and Gold Complexes into Cancer Cells

Abstract

Cisplatin and derivatives are highly effective in the treatment of a wide range of cancer types; however, these metallodrugs display low selectivity, leading to severe side effects. Additionally, their administration often results in the development of chemoresistance, which ultimately results in therapeutic failure. This scenario triggered the study of other transition metals with innovative pharmacological profiles as alternatives to platinum, ruthenium- (e.g., KP1339 and NAMI-A) and gold-based (e.g., Auranofin) complexes being among the most advanced in terms of clinical evaluation. Concerning the importance of improving the in vivo selectivity of metal complexes and the current relevance of ruthenium and gold metals, this review article aims to survey the main research efforts made in the past few years toward the design and biological evaluation of target-specific ruthenium and gold complexes. Herein, we give an overview of the inorganic and organometallic molecules conjugated to different biomolecules for targeting membrane proteins, namely cell adhesion molecules, G-protein coupled receptors, and growth factor receptors. Complexes that recognize the progesterone receptors or other targets involved in metabolic pathways such as glucose transporters are discussed as well. Finally, we describe some complexes aimed at recognizing cell organelles or compartments, mitochondria being the most explored. The few complexes addressing targeted gene therapy are also presented and discussed.

Gold Compounds Inhibit the Ca2+-ATPase Activity of Brain PMCA and Human Neuroblastoma SH-SY5Y Cells and Decrease Cell Viability

“…In fact, several inorganic compounds and complexes inhibit Ca 2+ -ATPases activity with IC 50 inhibition values similar to the well-known Ca 2+ -ATPases drugs inhibitors, for example decavanadate (IC 50 = 15 µM), polyoxotungstates (IC 50 = 0.3-200 µM), polyoxovanadates (IC 50 = 1 µM), and vanadium complexes, such as BMOV (IC 50 = 40 µM), among others [42][43][44][45][46][47][48]. In summary, both gold(I) and gold(III) compounds 1-4 are potent inhibitors of the PMCA, pointing out this enzyme as a putative target for gold compounds that are promising agents in medicinal chemistry [49][50][51].…”

“…The model used was previously applied to several inorganic compounds, including vanadate. In fact, several studies were described about the interaction of organic and inorganic compounds and their effects on P-type ATPases [23,[36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Therefore, several experiments with several vanadium compounds [45,47,48] at the same experimental conditions for comparison were performed, and the potencies of inhibition are compared in Table 2.…”

Ruthenium-based antitumor drugs and delivery systems from monotherapy to combination therapy

“…Many ruthenium nanoparticles enter the cell via receptor-mediated endocytosis, including cell adhesion molecule receptors (including integrin and calcemin), G-protein-coupled receptors, epidermal growth factor receptors, and other emerging molecular receptors (including progesterone receptor and glucose transporter) 199 .…”

Gold(i) metallocyclophosphazenes with antibacterial potency and antitumor efficacy. Synergistic antibacterial action of a heterometallic gold and silver-cyclophosphazene

“…The anticancer activity of gold(I) complexes has been summarized in recent reviews 20,25,28 and the IC 50 values obtained for some of the tested gold-phosphazenes are among the lowest found for any gold derivatives against MCF7 and HepG2 cell lines, taking into account the experimental conditions (measured at 48 h). 34,35 Phosphazenes 4 and 8 proved to be just as or more potent than the analogue silver metallophosphazenes mentioned before, whose IC 50 values are also shown in Table 4a and b for comparison.…”

“…26,27 Several reviews on this topic have recently appeared. 25,[28][29][30][31][32] These surveys indicate that the stability of the ligands coordinated to the metal centre is a critical issue for the design of gold-based drugs. Thus, in the case of gold(I), ligands with relatively high bond dissociation energies, such as phosphanes, 20,33 carbenes 19,30 or alkynes, 18,34,35 are privileged moieties.…”