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Synthesis, characterization and irradiation enhances anticancer activity of liposome-loaded iridium(III) complexes.
- Source :
-
Journal of inorganic biochemistry [J Inorg Biochem] 2024 Jul; Vol. 256, pp. 112549. Date of Electronic Publication: 2024 Apr 02. - Publication Year :
- 2024
-
Abstract
- Herein, we synthesized and characterized two novel iridium (III) complexes: [Ir(bzq) <subscript>2</subscript> (PPD)](PF <subscript>6</subscript> ) (4a, with bzq = deprotonated benzo[h]quinoline and PPD = pteridino[6,7-f][1,10]phenanthroline-11,13-diamine) and [Ir(piq) <subscript>2</subscript> (PPD)](PF <subscript>6</subscript> ) (4b, with piq = deprotonated 1-phenylisoquinoline). The anticancer efficacy of these complexes, 4a and 4b, was investigated using 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide (MTT). Complex 4a exhibited no cytotoxic activity, while 4b demonstrated moderate efficacy against SGC-7901, A549, and HepG2 cancer cells. To enhance their anticancer potential, we explored two strategies: (I) light irradiation and (II) encapsulation of the complexes in liposomes, resulting in the formation of 4alip and 4blip. Both strategies significantly increased the ability of 4a, 4b to kill cancer cells. The cellular studies indicated that both the free complexes 4a, 4b and their liposomal forms 4alip and 4blip effectively inhibited cell proliferation. The cell cycle arrest analysis uncovered 4alip and 4blip arresting cell growth in the S period. Additionally, we investigated apoptosis and ferroptosis pathways, observing an increase in malondialdehyde (MDA) levels, a reduction of glutathione (GSH), a down-regulation of GPX4 (glutathione peroxidase) expression, and lipid peroxidation. The effects on mitochondrial membrane potential and intracellular Ca <superscript>2+</superscript> concentrations were also examined, revealing that both light-activated and liposomal forms of 4alip and 4blip caused a decline in mitochondrial membrane potential and an enhancement in intracellular Ca <superscript>2+</superscript> levels. In conclusion, these complexes and them encapsulated liposomes induce cell death through apoptosis and ferroptosis.<br />Competing Interests: Declaration of competing interest The authors declare no competing interest exists.<br /> (Copyright © 2023. Published by Elsevier Inc.)
- Subjects :
- Humans
Cell Proliferation drug effects
Cell Line, Tumor
Membrane Potential, Mitochondrial drug effects
Liposomes
Iridium chemistry
Iridium pharmacology
Antineoplastic Agents pharmacology
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Coordination Complexes pharmacology
Coordination Complexes chemistry
Coordination Complexes chemical synthesis
Apoptosis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3344
- Volume :
- 256
- Database :
- MEDLINE
- Journal :
- Journal of inorganic biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38579631
- Full Text :
- https://doi.org/10.1016/j.jinorgbio.2024.112549