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Lysosome directed red light photodynamic therapy using glycosylated iron-(III) conjugates of boron-dipyrromethene

Sahoo, S and Pathak, S and Kumar, A and Nandi, D and Chakravarty, AR (2023) Lysosome directed red light photodynamic therapy using glycosylated iron-(III) conjugates of boron-dipyrromethene. In: Journal of Inorganic Biochemistry, 244 .

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Official URL: https://doi.org/10.1016/j.jinorgbio.2023.112226


To overcome the drawbacks associated with chemotherapeutic and porphyrin-based photodynamic therapy (PDT) agents, the use of BODIPY (boron-dipyrromethene) scaffold has gained prominence in designing a new generation of photosensitizers-cum-cellular imaging agents. However, their poor cell permeability and limited solubility in aqueous medium inhibits the in-vitro application of their organic form. This necessitates the development of metal-BODIPY conjugates with improved physiological stability and enhanced therapeutic efficacy. We have designed two iron(III)-BODIPY conjugates, Fe(L1/2)(L3)Cl derived from benzyl-dipicolylamine and its glycosylated analogue along with a BODIPY-tagged catecholate. The complexes showed intense absorption bands (ε ∼ 55,000 M−1 cm−1) and demonstrated apoptotic PDT activity upon red-light irradiation (30 J/cm2, 600–720 nm). The complex with singlet oxygen quantum yield value of ∼0.34 gave sub-micromolar IC50 (half-maximal inhibitory concentration) value (∼0.08 μM) in both HeLa and H1299 cancer cells with a photocytotoxicity index value of >1200. Both the complexes were found to have significantly lower cytotoxic effects in non-cancerous HPL1D (human peripheral lung epithelial) cells. Singlet oxygen was determined to be the prime reactive oxygen species (ROS) responsible for cell damage from pUC19 DNA photo-cleavage studies, 1,3-diphenylisobenzofuran and SOSG (Singlet Oxygen Sensor Green) assays. Cellular imaging studies showed excellent fluorescence from complex 2 within 4 h, with localization in lysosomes. Significant drug accumulation into the core of 3D multicellular tumor spheroids was observed within 8 h from intense in-vitro emission. The complexes exemplify iron-based targeted PDT agents and show promising results as potential transition metal-based drugs for ROS mediated red light photocytotoxicity with low dosage requirement. © 2023

Item Type: Journal Article
Publication: Journal of Inorganic Biochemistry
Publisher: Elsevier Inc.
Additional Information: The copyright of the article belongs to Elsevier Inc.
Keywords: Boron-dipyrromethene; Cellular apoptosis; Iron catecholates; Lysosomal localization; Medicinal chemistry; Photodynamic therapy in red light
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Chemical Sciences > Inorganic & Physical Chemistry
Date Deposited: 14 Jun 2023 08:34
Last Modified: 14 Jun 2023 08:34
URI: https://eprints.iisc.ac.in/id/eprint/81868

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