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)-polypyridylbased 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.

Highly charged Ru(II) polypyridyl complexes as photosensitizer agents in photodynamic therapy of epithelial ovarian cancer cells / Conti, Luca; Giacomazzo, Gina Elena; Valtancoli, Barbara; Perfetti, Mauro; Privitera, Alberto; Giorgi, Claudia; Sfragano, Patrick Severin; Palchetti, Ilaria; Pecchioli, Sara; Bruni, Paola; Cencetti, Francesca. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - ELETTRONICO. - 23:(2022), pp. 13302-13320. [10.3390/ijms232113302]

Highly charged Ru(II) polypyridyl complexes as photosensitizer agents in photodynamic therapy of epithelial ovarian cancer cells

Conti, Luca
Writing – Original Draft Preparation
;
Giacomazzo, Gina Elena
Investigation
;
Valtancoli, Barbara
Funding Acquisition
;
Perfetti, Mauro
Membro del Collaboration Group
;
Privitera, Alberto
Membro del Collaboration Group
;
Giorgi, Claudia
Supervision
;
Sfragano, Patrick Severin
Membro del Collaboration Group
;
Palchetti, Ilaria
Membro del Collaboration Group
;
Pecchioli, Sara
Investigation
;
Bruni, Paola
Funding Acquisition
;
Cencetti, Francesca
Writing – Original Draft Preparation
2022

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)-polypyridylbased 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.
23
13302
13320
Conti, Luca; Giacomazzo, Gina Elena; Valtancoli, Barbara; Perfetti, Mauro; Privitera, Alberto; Giorgi, Claudia; Sfragano, Patrick Severin; Palchetti, Ilaria; Pecchioli, Sara; Bruni, Paola; Cencetti, Francesca
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1289184
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