Highly Charged Ru(II) Polypyridyl Complexes as Photosensitizer Agents in Photodynamic Therapy of Epithelial Ovarian Cancer Cells

Abstract

Ovarian cancer recurrence is frequent and associated with chemoresistance, leading to extremely poor prognosis. Herein, we explored the potential anti-cancer effect of a series of highly charged Ru(II)-polypyridyl complexes as photosensitizers in photodynamic therapy (PDT), which were able to efficiently sensitize the formation of singlet oxygen upon irradiation (Ru12+ and Ru22+) and to produce reactive oxygen species (ROS) in their corresponding dinuclear metal complexes with the Fenton active Cu(II) ion/s ([CuRu1]4+ and [Cu2Ru2]6+). Their cytotoxic and anti-tumor effects were evaluated on human ovarian cancer A2780 cells both in the absence or presence of photoirradiation, respectively. All the compounds tested were well tolerated under dark conditions, whereas they switched to exert anti-tumor activity following photoirradiation. The specific effect was mediated by the onset of programed cell death, but only in the case of Ru12+ and Ru22+ was preceded by the loss of mitochondrial membrane potential soon after photoactivation and ROS production, thus supporting the occurrence of apoptosis via type II photochemical reactions. Thus, Ru(II)-polypyridyl-based photosensitizers represent challenging tools to be further investigated in the identification of new therapeutic approaches to overcome the innate chemoresistance to platinum derivatives of some ovarian epithelial cancers and to find innovative drugs for recurrent ovarian cancer.

Ruthenium(ii) polypyridyl complexes with π-expansive ligands: synthesis and cubosome encapsulation for photodynamic therapy of non-melanoma skin cancer

“…[5][6][7][8] The interest towards this versatile class of compounds can be attributed to its rich chemical-physical repertoire, which includes a variety of excited-state electronic configurations accessible with light, good singlet oxygen sensitizing properties, and the capacity to interact with key biological targets (such as DNA or proteins). [9][10][11] Of relevance is that a fine choice of ligands in their octahedral geometries permits convenient modulation of the photophysical, photochemical, and photobiological properties of the resulting RPCs, in an effort to improve cellular uptake, 12,13 shift the absorption profiles towards red, 14 confer targeting ability, 15,16 and boost 1 O 2 sensitization. With regard to the latter aim, as prolonged excited state lifetimes are important for efficient energy transfer to molecular oxygen to form 1 O 2 , changing the nature of the lowest-lying excited state from metal-to-ligand charge-transfer ( 3 MLCT) to long-lived intraligand 3 IL states represents a suitable way to endow the resulting RPCs with augmented cytotoxicity.…”

Ruthenium(II) Polypyridyl Complexes and Metronidazole Derivatives: A Powerful Combination in the Design of Photoresponsive Antibacterial Agents Effective under Hypoxic Conditions

“…Recently, the encouraging results obtained in the design of antitumoral agents − have renewed the interest in Ru­(II)-polypyridyl complexes (RPCs), a versatile class of compounds whose antibacterial potential was first reported over 70 years ago. , Their rich chemical–physical repertoire, which includes versatile optical and luminescent properties, capacity to interact with key biological targets, and amenability to synthetic tailoring (just to name a few), has been indeed exploited to develop new classes of antibacterial agents. − Of particular relevance is the combination of RPCs with light in the so-called antimicrobial photodynamic therapy (aPDT), − a technique that relies on the irradiation of a photosensitizer (RPCs) to promote the generation of highly cytotoxic reactive oxygen species (ROS). − Besides ROS sensitization, whose effectiveness against both sensitive and multidrug-resistant bacteria has been reported, , the main advantage of aPDT consists in the complete spatiotemporal control over the drug activation, which offers the important chance to overcome overdose and side effect issues normally associated with the systemic administration of antimicrobials. However, the reliance of aPDT on molecular oxygen still threatens its application to hypoxic environments, such as anaerobic infections .…”

“…Recently, the encouraging results obtained in the design of antitumoral agents 15 − 20 have renewed the interest in Ru(II)-polypyridyl complexes (RPCs), a versatile class of compounds whose antibacterial potential was first reported over 70 years ago. 21 , 22 Their rich chemical–physical repertoire, which includes versatile optical and luminescent properties, capacity to interact with key biological targets, and amenability to synthetic tailoring (just to name a few), has been indeed exploited to develop new classes of antibacterial agents.…”