Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts

Mandal, AA and Singh, V and Saha, S and Peters, S and Sadhukhan, T and Kushwaha, R and Yadav, AK and Mandal, A and Upadhyay, A and Bera, A and Dutta, A and Koch, B and Banerjee, S (2024) Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts. In: Inorganic Chemistry, 63 (16).

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Abstract

The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA). Recently, photocatalytic cancer therapy, an intrusive catalytic treatment, is receiving significant interest due to its multitargeting cell death mechanism with high selectivity. Here, we report the synthesis and characterization of three photoresponsive Ru(II) complexes, viz., Ru(ph-tpy)(bpy)ClPF6 (Ru1), Ru(ph-tpy)(phen)ClPF6 (Ru2), and Ru(ph-tpy)(aip)ClPF6 (Ru3), where, ph-tpy = 4�-phenyl-2,2�:6�,2�-terpyridine, bpy = 2,2�-bipyridine, phen = 1,10-phenanthroline, and aip = 2-(anthracen-9-yl)-1H-imidazo4,5-f1,10 phenanthroline, showing photocatalytic anticancer activity. The X-ray crystal structures of Ru1 and Ru2 revealed a distorted octahedral geometry with a RuN5Cl core. The complexes showed an intense absorption band in the 440-600 nm range corresponding to the metal-to-ligand charge transfer (MLCT) that was further used to achieve the green light-induced photocatalytic anticancer effect. The mitochondria-targeting photostable complex Ru3 induced phototoxicity with IC50 and PI values of ca. 0.7 μM and 88, respectively, under white light irradiation and ca. 1.9 μM and 35 under green light irradiation against HeLa cells. The complexes (Ru1-Ru3) showed negligible dark cytotoxicity toward normal splenocytes (IC50s > 50 μM). The cell death mechanistic study revealed that Ru3 induced ROS-mediated apoptosis in HeLa cells via mitochondrial depolarization under white or green light exposure. Interestingly, Ru3 also acted as a highly potent catalyst for NADH photo-oxidation under green light. This NADH photo-oxidation process also contributed to the photocytotoxicity of the complexes. Overall, Ru3 presented multitargeting synergistic type I and type II photochemotherapeutic effects. © 2024 American Chemical Society.

Item Type:	Journal Article
Publication:	Inorganic Chemistry
Publisher:	American Chemical Society
Additional Information:	The copyright for this article belongs to American Chemical Society.
Keywords:	Charge transfer; Diseases; Irradiation; Lanthanum compounds; Mitochondria; Oncology; Photocatalytic activity; Ruthenium compounds; Synthesis (chemical), Anticancer activities; Cancer therapy; Drug-resistance; Green light; HeLa cell; Mechanism of action; Phenanthrolines; Photo oxidation; Photo-catalytic; Terpyridines, Cell death, nicotinamide adenine dinucleotide; ruthenium, chemistry; HeLa cell line; human; photochemotherapy, Green Light; HeLa Cells; Humans; NAD; Photochemotherapy; Ruthenium
Department/Centre:	Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	28 Aug 2024 06:20
Last Modified:	28 Aug 2024 06:20
URI:	http://eprints.iisc.ac.in/id/eprint/84892

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