Functionalization and cancer-targeting design of ruthenium complexes for precise cancer therapy

Liu, Jinggong; Lai, Haoqiang; Xiong, Zushuang; Chen, Bolai; Chen, Tianfeng

doi:10.1039/c9cc04098f

Cited by 120 publications

(98 citation statements)

References 136 publications

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“…with a positive charge are ideal candidates for mitochondria-targeting RSs since heavy metals with high-Z are sensitive to X-rays and positively charged materials tend to accumulate in mitochondria. 16,17 Despite the fact that using lipophilic heavy metal complexes with a positive charge as RSs can well combat the deciencies of DNA-targeting RSs, the lack of visualization of tumor sites and the low bioavailability of RSs also hinder their application. Cyclometalated iridium-based (Ir, Z ¼ 77) materials would be promising candidates for the design of novel RSs with bioimaging function due to their long-lived luminescence, good light stability and also photophysical sensitivity to acidity, oxygen content or viscosity.…”

Section: Introductionmentioning

confidence: 99%

A highly X-ray sensitive iridium prodrug for visualized tumor radiochemotherapy

Zhao

Gao

et al. 2020

Chem. Sci.

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Section: Introductionmentioning

confidence: 99%

A highly X-ray sensitive iridium prodrug for visualized tumor radiochemotherapy

Zhao

Gao

et al. 2020

Chem. Sci.

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“…As one of the most promising alternatives to platinum-based chemotherapeutics are Ru(II) and Ru(III) complexes. They possess unique multifunctional biochemical properties and exhibit lower toxic effects than platinum-based chemotherapeutics [14,15]. In cancer cells, trivalent Ru complexes are speculated to be reduced by cellular reductants, e.g., ascorbates, to their more active divalent form.…”

Section: Introductionmentioning

confidence: 99%

“…For the majority of Ru complexes, the cellular mode of action differs from the DNA-binding mechanism, which is typically associated with platinum-based chemotherapeutics [16]. Despite the wide range of intracellular targets, only two Ru complexes-KP1339, which is the sodium salt analogue of KP1019 (indazolium trans-[tetrachlorobis(1H-indazole)-ruthenate(III)]) and TLD1433 ([Ru(II) (4,4′-dimethyl-2,2′bipyridine)2(2-(2′,2′′:5′′,2′′′-terthiophene)-imidazo[4,5-f])]Cl2)-are currently in the clinical trials [2,[15][16][17]. While Ru(III) complexes KP1339 have been developed as chemotherapeutic agents, the octahedral Ru(II) complex TLD1433 exhibits potential for photo-dynamic therapy [16].…”

Section: Introductionmentioning

confidence: 99%

Binding Kinetics of Ruthenium Pyrithione Chemotherapeutic Candidates to Human Serum Proteins Studied by HPLC-ICP-MS

et al. 2020

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The development of ruthenium-based complexes for cancer treatment requires a variety of pharmacological studies, one of them being a drug’s binding kinetics to serum proteins. In this work, speciation analysis was used to study kinetics of ruthenium-based drug candidates with human serum proteins. Two ruthenium (Ru) complexes, namely [(η6-p-cymene)Ru(1-hydroxypyridine-2(1H)-thionato)Cl] (1) and [(η6-p-cymene)Ru(1-hydroxypyridine-2(1H)-thionato)pta]PF6 (2) (where pta = 1,3,5-triaza-7-phosphaadamantane), were selected. Before a kinetics study, their stability in relevant media was confirmed by nuclear magnetic resonance (NMR). Conjoint liquid chromatography (CLC) monolithic column, assembling convective interaction media (CIM) protein G and diethylamino (DEAE) disks, was used for separation of unbound Ru species from those bound to human serum transferrin (Tf), albumin (HSA) and immunoglobulins G (IgG). Eluted proteins were monitored by UV spectrometry (278 nm), while Ru species were quantified by post-column isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). Binding kinetics of chlorido (1) and pta complex (2) to serum proteins was followed from 5 min up to 48 h after incubation with human serum. Both Ru complexes interacted mainly with HSA. Complex (1) exhibited faster and more extensive interaction with HSA than complex (2). The equilibrium concentration for complex (1) was obtained 6 h after incubation, when about 70% of compound was bound to HSA, 5% was associated with IgG, whereas 25% remained unbound. In contrast, the rate of interaction of complex (2) with HSA was much slower and less extensive and the equilibrium concentration was obtained 24 h after incubation, when about 50% of complex (2) was bound to HSA and 50% remained unbound.

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“…The development of new antitumor drugs requires understanding the mechanisms of action of new pharmacological candidates, which highlights the importance of elucidating the molecular and biochemical mechanisms involved. Recent studies have shown that some ruthenium complexes target the genomic DNA and may cause cell cycle arrest, ROS-mediated mitochondrial alterations and, finally, cell death by apoptosis 3,[7][8][9] .…”

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confidence: 99%

Ruthenium (II) complex cis-[RuII(ŋ2-O2CC7H7O2)(dppm)2]PF6-hmxbato induces ROS-mediated apoptosis in lung tumor cells producing selective cytotoxicity

Costa

Gonçalves

Borges

et al. 2020

Sci Rep

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Ruthenium complexes have been extensively explored as potential molecules for cancer treatment. Considering our previous findings on the remarkable cytotoxic activity exhibited by the ruthenium (II) complex 3-hydroxy-4-methoxybenzoate (hmxbato)-cis-[RuII(ŋ2-O2CC7H7O2)(dppm)2]PF6 against Leishmania promastigotes and also the similar metabolic characteristics between trypanosomatids and tumor cells, the present study aimed to analyze the anticancer potential of hmxbato against lung tumor cells, as well as the partial death mechanisms involved. Hmxbato demonstrated selective cytotoxicity against A549 lung tumor cells. In addition, this complex at a concentration of 3.8 µM was able to expressively increase the generation of reactive oxygen species (ROS) in tumor cells, causing an oxidative stress that may culminate in: (1) reduction in cellular proliferation; (2) changes in cell morphology and organization patterns of the actin cytoskeleton; (3) cell arrest in the G2/M phase of the cell cycle; (4) apoptosis; (5) changes in the mitochondrial membrane potential and (6) initial DNA damage. Furthermore, we demonstrated that the induction of programmed cell death can occur by the intrinsic apoptotic pathway through the activation of caspases. It is also worth highlighting that hmxbato exhibited predominant actions on A549 tumor cells in comparison to BEAS-2B normal bronchial epithelium cells, which makes this complex an interesting candidate for the design of new drugs against lung cancer.

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Functionalization and cancer-targeting design of ruthenium complexes for precise cancer therapy

Abstract: Herein, the functionalized Ruthenium complex applied for bio-imaging, photodynamic/photothermal therapy, precise targeted therapy and theranostics application have been discussed.

Cited by 120 publications

References 136 publications

A highly X-ray sensitive iridium prodrug for visualized tumor radiochemotherapy

A highly X-ray sensitive iridium prodrug for visualized tumor radiochemotherapy

Binding Kinetics of Ruthenium Pyrithione Chemotherapeutic Candidates to Human Serum Proteins Studied by HPLC-ICP-MS

Ruthenium (II) complex cis-[RuII(ŋ2-O2CC7H7O2)(dppm)2]PF6-hmxbato induces ROS-mediated apoptosis in lung tumor cells producing selective cytotoxicity

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