4.1 Article

Photoactivated cytotoxicity induced by heterobimetallic Ru(II)-Pt(II) polypyridyl complexes in MCF-7 cells

Journal

JOURNAL OF CHEMICAL SCIENCES
Volume 133, Issue 3, Pages -

Publisher

INDIAN ACAD SCIENCES
DOI: 10.1007/s12039-021-01935-0

Keywords

Photosensitizer; heterobimetallic complexes; photocytotoxicity; autophagy

Funding

  1. University Grant Commission under Centre for Advance Studies CAS-IV [F.540/11/CAS-IV/2016 (SAP-I)]
  2. SERB, India [CRG/2018/001882]
  3. Agharkar Research Institute [ZOO-17]
  4. Council of Scientific and Industrial Research (CSIR)
  5. Institute Postdoctoral Fellowship (IPDF), IIT Bombay

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By incorporating the photosensitizer Ru(II) polypyridyl complexes into the cis-PtCl2 moiety, the anticancer properties of the complexes were improved, leading to increased cytotoxicity against MCF-7 cells and potential candidacy for Photodynamic Therapy.
The heterobimetallic Ru(II)-Pt(II) polypyridyl complexes [Ru(bpy)(2)(BPIMBp)PtCl2](2+) (3) and [Ru(phen)(2)(BPIMBp)PtCl2](2+) (4) with their parent complexes [Ru(bpy)(2)BPIMBp](2+)(1) and [Ru(phen)(2)BPIMBp](2+) (2) possessing bridging ligand (BPIMBp = 1,4 '-Bis-{(2-pyridin-2-yl)-1H-imidazol-1-yl)methyl}-1,1 '-biphenyl) were used for photocytotoxicity against MCF-7 cells.The parent ruthenium complexes (complexes 1-2) exhibited a negligible increase in viscosity of DNA while heterobimetallic Ru(II)-Pt(II) system exhibited a decrease in viscosity of DNA, indicating covalent interaction (through cis-PtCl2 unit). The Ru(II)-Pt(II) system co-precipitated with CT-DNA confirmed the covalent binding. In electrophoretic mobility studies, the interaction of Ru(II)-Pt(II) system with plasmid DNA led to retardation of negative supercoiled form, followed by positive supercoiled migration in the dark that indicated the ability to form covalent adducts with DNA similar to cisplatin. The complexes 1-4 showed enhanced photocleavage of plasmid DNA on blue light (similar to 450 nm) irradiation. In a cell-based study, all the complexes exhibited photoactivated cytotoxicity in MCF-7 cancer cells when exposed to visible light of similar to 450 nm as compared to low toxicity in absence of irradiation. Additionally, the complexes containing platinum showed induction of autophagy in GFP-LC3 expressing MCF-7 cells. Overall our study shows that the inclusion of photosensitizer Ru(II) polypyridyl complexes to cis-PtCl2 moiety improves anticancer properties of complexes. Graphic abstract The effect of Ru(II)-Pt(II) polypyridyl complexes as photosensitizers was studied against MCF-7 cells. The complexes are negligibly toxic to MCF-7 cells in the dark while highly cytotoxic towards MCF-7 cells on irradiation of blue light (similar to 450 nm). Therefore, the complexes could be potential candidates for Photodynamic Therapy.

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