Red light active Pt(iv)-BODIPY prodrug as a mitochondria and endoplasmic reticulum targeted chemo-PDT agent

Bera, A and Gautam, S and Sahoo, S and Pal, AK and Kondaiah, P and Chakravarty, AR (2022) Red light active Pt(iv)-BODIPY prodrug as a mitochondria and endoplasmic reticulum targeted chemo-PDT agent. In: RSC Medicinal Chemistry .

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Abstract

A cisplatin-based platinum(iv) prodrug, [Pt(NH3)2Cl2(OH)(L1)], having L1 as a red-light active boron-dipyrromethene (BODIPY) pendant, was synthesized and characterized and its application as a chemo-cum-photodynamic therapy agent was studied. Me-L1 as the ligand precursor is structurally characterized. The complex displayed an intense absorption band near 650 nm (ϵ ∼ 8.8 × 104 dm3 mol−1 cm−1) in 1 : 1 (v/v) DMSO/DPBS. It showed an emission band at 674 nm (λex = 630 nm) with a fluorescence quantum yield (ΦF) value of 0.37. In red light (600-720 nm), it generated singlet oxygen as evidenced from the 1,3-diphenylisobenzofuran (DPBF) titration experiment giving a singlet oxygen quantum yield (ΦΔ) value of 0.28 in DMSO. The mechanistic pUC19 DNA photocleavage study and singlet oxygen sensor green (SOSG) assay ascertained its ability to generate singlet oxygen in both extracellular and intracellular media by a type-II photo-process. The complex exhibited high stability in the dark, but on red-light irradiation, it displayed rapid activation in the presence of a reducing environment. It displayed remarkable apoptotic photocytotoxicity with half-maximal inhibitory concentration (IC50) ranging from 0.58 to 0.76 μM in human cervical cancer (HeLa) and breast cancer (MCF-7) cells with a respective photo-cytotoxicity index value of >172 and >131. The photodynamic activity was significantly less in non-cancerous human peripheral lung epithelial (HPL1D) cells. The emissive complex showed localization in the mitochondria and endoplasmic reticulum (ER) with a similar Pearson's correlation coefficient value, making it a dual organelle-targeted therapeutic agent. JC-1, fluo-4-AM and annexin V-FITC/propidium iodide assays in HeLa cells showed cellular apoptosis by arresting cells in the sub-G1 phase via mitochondrial dysfunction and ER stress.

Item Type:	Journal Article
Publication:	RSC Medicinal Chemistry
Publisher:	Royal Society of Chemistry
Additional Information:	The copyright for this article belongs to Royal Society of Chemistry.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited:	02 Nov 2022 05:21
Last Modified:	02 Nov 2022 05:21
URI:	https://eprints.iisc.ac.in/id/eprint/77782

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