Biotin and boron-dipyrromethene-tagged platinum(iv) prodrug for cellular imaging and mito-targeted photocytotoxicity in red light

Bera, A and Nepalia, A and Upadhyay, A and Kumar Saini, D and Chakravarty, AR (2023) Biotin and boron-dipyrromethene-tagged platinum(iv) prodrug for cellular imaging and mito-targeted photocytotoxicity in red light. In: Dalton Transactions, 52 (37). pp. 13339-13350.

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Abstract

A platinum(iv) prodrug, cis,cis,trans-[Pt(NH3)2Cl2(biotin)(L)] (1), derived from cisplatin, where HL is the PEGylated red-light active boron-dipyrromethene (BODIPY) ligand, was synthesized, characterized and its photocytotoxicity evaluated. The complex showed a near-IR absorption band at 653 nm (ϵ ∼9.19 × 104 M−1 cm−1) in dimethyl sulfoxide and Dulbecco's phosphate-buffered saline (1 : 1 v/v) at pH 7.2. When excited at 630 nm, it showed an emission band at 677 nm in DMSO with a fluorescence quantum yield of 0.13. The 1,3-diphenylisobenzofuran titration experiment gave a singlet oxygen quantum yield (ΦΔ) of ∼0.32. A mechanistic DNA photocleavage study revealed singlet oxygen as the reactive oxygen species (ROS). The complex with biotin and PEGylated-distyryl-BODIPY showed significantly higher cellular uptake in A549 cancer cells as compared to non-cancerous Beas-2B cells from flow cytometry, indicating selectivity towards cancer cells. A dichlorodihydrofluorescein diacetate assay showed cellular ROS generation. Confocal images revealed predominant internalization in the mitochondria. The prodrug showed remarkable photodynamic therapy (PDT) activity in cancerous A549 and multidrug-resistant MDA-MB-231 cells with a high photocytotoxicity index value (half-maximal inhibitory concentration (IC50): 0.61-1.54 μM in red light), while being non-toxic in the dark. The chemo-PDT activity was significantly less in non-tumorigenic lung epithelial cells (Beas-2B). The prodrug effectively triggered cellular apoptosis, which was confirmed by the Annexin V-FITC/propidium iodide assay, and the alteration of the mitochondrial membrane potential was substantiated by the JC-1 dye assay. The β-tubulin immunofluorescence assay confirmed that incubating the cells with a light-treated complex resulted in the rapture of the cytoskeletal structure and the formation of apoptotic bodies. The results demonstrate that the prodrug triggered apoptosis via DNA damage, a reduction in mitochondrial function and disruption of the cytoskeletal framework. © 2023 The Royal Society of Chemistry.

Item Type:	Journal Article
Publication:	Dalton Transactions
Publisher:	Royal Society of Chemistry
Additional Information:	The copyright for this article belongs to the Royal Society of Chemistry.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	24 Nov 2023 05:22
Last Modified:	24 Nov 2023 05:22
URI:	https://eprints.iisc.ac.in/id/eprint/83246

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