Photo-induced cytotoxicity and anti-metastatic activity of ruthenium(<scp>ii</scp>)–polypyridyl complexes functionalized with tyrosine or tryptophan

Ramu, Vadde; Aute, Sunil; Taye, Nandaraj; Guha, Rweetuparna; Walker, Michael G.; Mogare, Devaraj; Parulekar, Apoorva; Thomas, Jim A.; Chattopadhyay, Samit; Das, Amitava

doi:10.1039/c7dt00670e

Cited by 27 publications

(15 citation statements)

References 54 publications

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“…Besides tetrapyrole compounds and their precursors (5-ALA), the metal-based PDT PS, in particular those containing ruthenium(II) (Ru), show a high potential for generating intracellular ROS [26]. These PS absorb in the visible region of the spectrum, which is critical for in vivo activation [27], and suffer less from photobleaching compared to many tetrapyrole compounds [28,29].…”

Section: Introductionmentioning

confidence: 99%

TLD1433 Photosensitizer Inhibits Conjunctival Melanoma Cells in Zebrafish Ectopic and Orthotopic Tumour Models

Chen

Ramu

Aydar

et al. 2020

Cancers

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The ruthenium-based photosensitizer (PS) TLD1433 has completed a phase I clinical trial for photodynamic therapy (PDT) treatment of bladder cancer. Here, we investigated a possible repurposing of this drug for treatment of conjunctival melanoma (CM). CM is a rare but often deadly ocular cancer. The efficacy of TLD1433 was tested on several cell lines from CM (CRMM1, CRMM2 and CM2005), uveal melanoma (OMM1, OMM2.5, MEL270), epidermoid carcinoma (A431) and cutaneous melanoma (A375). Using 15 min green light irradiation (21 mW/cm2, 19 J.cm−2, 520 nm), the highest phototherapeutic index (PI) was reached in CM cells, with cell death occurring via apoptosis and necrosis. The therapeutic potential of TLD1433 was hence further validated in zebrafish ectopic and newly-developed orthotopic CM models. Fluorescent CRMM1 and CRMM2 cells were injected into the circulation of zebrafish (ectopic model) or behind the eye (orthotopic model) and 24 h later, the engrafted embryos were treated with the maximally-tolerated dose of TLD1433. The drug was administrated in three ways, either by (i) incubating the fish in drug-containing water (WA), or (ii) injecting the drug intravenously into the fish (IV), or (iii) injecting the drug retro-orbitally (RO) into the fish. Optimally, four consecutive PDT treatments were performed on engrafted embryos using 60 min drug-to-light intervals and 90 min green light irradiation (21 mW/cm2, 114 J.cm−2, 520 nm). This PDT protocol was not toxic to the fish. In the ectopic tumour model, both systemic administration by IV injection and RO injection of TLD1433 significantly inhibited growth of engrafted CRMM1 and CRMM2 cells. However, in the orthotopic model, tumour growth was only attenuated by localized RO injection of TLD1433. These data unequivocally prove that the zebrafish provides a fast vertebrate cancer model that can be used to test the administration regimen, host toxicity and anti-cancer efficacy of PDT drugs against CM. Based on our results, we suggest repurposing of TLD1433 for treatment of incurable CM and further testing in alternative pre-clinical models.

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Section: Introductionmentioning

confidence: 99%

TLD1433 Photosensitizer Inhibits Conjunctival Melanoma Cells in Zebrafish Ectopic and Orthotopic Tumour Models

Chen

Ramu

Aydar

et al. 2020

Cancers

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“…Recent advances in discovering improved selectivity and cytotoxic activity of photocaged complexes led to in vitro testing of various ruthenium(II) complexes after their photoactivation by UVA and visible light (77)(78)(79)(80)(81)(82)(83)(84)(85). In general, after the excitation of the photosensitizing agent's moiety at suitable wavelength, energy or electron transfer process ultimately lead to the production of ROS which are cytotoxic to living cells and can be used for targeted singlet oxygen chemotherapy (77). Photocaged Ru complexes are usually nontoxic to nonirradiated tissues and can become toxic in tumor cells through photoactivation (78)(79)(80)(81)(82)(83)(84).…”

Section: Ru(ii) Complexes Which Entered Preclinical and Clinical Trialsmentioning

confidence: 99%

Ruthenium(II) Complexes as Potential Apoptosis Inducers in Cancer Therapy

Zarić

Pirković

Hamzagic³

2024

Experimental and Applied Biomedical Research (EABR)

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The compound cis-diamminedichloroplatinum(II) (cisplatin) is the most widely used anticancer drug, but due to its serious side effects (including gastrointestinal symptoms, renal tubular injury, neuromuscular complications, and ototoxicity), clinical applications of cisplatin are limited. Therefore, these limitations have provided an encouragement for further research into other transition metal complexes, with an aim to overcome the disadvantages related with cisplatin therapy. In the search for effective complexes that can be targeted against tumor cells, many research groups synthesized various ruthenium( II) complexes with different ligands. Also, newly synthesized ruthenium(II) complexes showed selective anticancer activity against different types of cancer cells. Activity of ruthenium(II) complexes in some cases was even higher than that of cisplatin against the same cells. Precise mechanism of action of ruthenium(II) complexes is not fully understood. The different examples mentioned in this review showed that ruthenium(II) complexes decreased viability of cancer cells by induction of apoptosis and/or by cell cycle arrest which implies their different mechanism of action against different types of cancer cells.

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“…Two Ru(II) polypyridyl compounds that target mitochondria functionalized with tyrosine and tryptophan were designed in 2013 ( Figure 4). 27 Both amino acids were chosen to improve the cellular uptake of the Ru complexes. An interesting study was recently published by the same group, who designed mitochondrialocalising Ru(II) complexes that can be activated by glutathione (GSH).…”

Section: Mitochondria Targeting Compoundsmentioning

confidence: 99%

Mechanisms of action of Ru(ii) polypyridyl complexes in living cells upon light irradiation

et al. 2018

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Photo-induced cytotoxicity and anti-metastatic activity of ruthenium(ii)–polypyridyl complexes functionalized with tyrosine or tryptophan

Abstract: The synergestic effect of oxygen, light, and photosensitizer has found application in photodyanmic therapy (PDT).

Cited by 27 publications

References 54 publications

TLD1433 Photosensitizer Inhibits Conjunctival Melanoma Cells in Zebrafish Ectopic and Orthotopic Tumour Models

TLD1433 Photosensitizer Inhibits Conjunctival Melanoma Cells in Zebrafish Ectopic and Orthotopic Tumour Models

Ruthenium(II) Complexes as Potential Apoptosis Inducers in Cancer Therapy

Mechanisms of action of Ru(ii) polypyridyl complexes in living cells upon light irradiation

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