Recent advances in cytotoxicity, cellular uptake and mechanism of action of ruthenium metallodrugs: A review

Are smart delivery systems the solution to overcome the lack of selectivity of current metallodrugs in cancer therapy?

“…9,73 Over the past years, ruthenium complexes have emerged as a paradigmatic example of potential alternatives to platinumbased drugs, replicating or even surpassing cisplatin efficacy while overcoming some of its main drawbacks, and now representing the second most studied class of anticancer metal complexes. 9,74,75 In particular, ruthenium may offers attractive chemical and pharmacological properties when compared with platinum, including a higher number of coordination positions available for the exploitation of a vaster quantity of ligands, different oxidation states accessible under physiologi-cal conditions, alternative coordination geometries, low ligand exchange rates with kinetics on the timescale of cell processes, a high affinity towards nitrogen and sulfur atoms often present in proteins and other biological targets, high cytotoxicity, and fluorescence properties, among many others. [74][75][76] Indeed, several ruthenium complexes have been reported to show desirable in vitro and in vivo antitumoral and/or antimetastatic activity through different mechanisms of action that obviate resistance to platinum drugs, as well as having fewer and less severe side effects.…”

“…9,74,75 In particular, ruthenium may offers attractive chemical and pharmacological properties when compared with platinum, including a higher number of coordination positions available for the exploitation of a vaster quantity of ligands, different oxidation states accessible under physiologi-cal conditions, alternative coordination geometries, low ligand exchange rates with kinetics on the timescale of cell processes, a high affinity towards nitrogen and sulfur atoms often present in proteins and other biological targets, high cytotoxicity, and fluorescence properties, among many others. [74][75][76] Indeed, several ruthenium complexes have been reported to show desirable in vitro and in vivo antitumoral and/or antimetastatic activity through different mechanisms of action that obviate resistance to platinum drugs, as well as having fewer and less severe side effects. [74][75][76][77][78] Moreover, some ruthenium complexes also demonstrated appropriate behaviour for cancer imaging and/or theranostics.…”

“…[74][75][76] Indeed, several ruthenium complexes have been reported to show desirable in vitro and in vivo antitumoral and/or antimetastatic activity through different mechanisms of action that obviate resistance to platinum drugs, as well as having fewer and less severe side effects. [74][75][76][77][78] Moreover, some ruthenium complexes also demonstrated appropriate behaviour for cancer imaging and/or theranostics. 76,79 Although such results are encouraging, approval for a ruthenium-based drug for clinical use has not yet been achieved.…”

Two out of Three Musketeers Fight against Cancer: Synthesis, Physicochemical, and Biological Properties of Phosphino CuI, RuII, IrIII Complexes

“…It has been reported that the cellular uptake efficacy of a compound is affected by many factors, such as lipophilicity [62][63][64]. Synthesized complexes indicate blue fluorescence.…”

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

“…Ruthenium and gold complexes are among the most investigated and advanced non-platinum based metallodrugs in terms of clinical evaluation and the study of the respective mechanisms of action. To date, four Ru complexes, namely KP1019 and its sodium analog KP1339 as well as NAMI-A and TLD1433 ( Figure 1 ), have entered clinical evaluation as systemic anticancer therapeutics [ 2 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. Gold complexes emerged as well as suitable antiproliferative agents due to their mechanism of action [ 3 , 4 , 5 , 34 ].…”