Phototoxicity of Tridentate Ru(II) Polypyridyl Complex with Expanded Bite Angles toward Mammalian Cells and Multicellular Tumor Spheroids
Tridentate ligand-coordinated ruthenium (II) polypyridyl complexes with large N-Ru-N bite angles have been shown to promote ligand field splitting and reduce singlet-triplet state mixing leading to dramatically extended emission quantum yields and lifetimes under ambient conditions. These effects are anticipated to enhance their photoinduced singlet oxygen production, promoting prospects for such complexes as type II phototherapeutics. In this contribution, we examined this putative effect for [Ru(bqp)(bqpCOOEt)]2+, Ru-bqp-ester, a heteroleptic complex containing bqp = [2,6-bi(quinolin-8-yl)pyridine], a well-established large bite angle tridentate ligand, as well as its peptide conjugates [Ru(bqp)(bqpCONH-ahx-FrFKFrFK(Ac)-CONH2)]5+ (Ru-bqp-MPP) and [Ru(bqp) (bqp)(CONH-ahx-RRRRRRRR-CONH2)]10+ (Ru-bqp-R8) that were prepared in an effort to promote live cell/tissue permeability and targeting of the parent. Membrane permeability of both parent and peptide conjugates were compared across 2D cell monolayers; A549, Chinese hamster ovary, human pancreatic cancer (HPAC), and 3D HPAC multicellular tumor spheroids (MCTS) using confocal microscopy. Both the parent complex and peptide conjugates showed exceptional permeability with rapid uptake in both 2D and 3D cell models but with little distinction in permeability or distribution in cells between the parent or peptide conjugates. Unexpectedly, the uptake was temperature independent and so attributed to passive permeation. Both dark and photo-toxicity of the Ru(II) complexes were assessed across cell types, and the parent showed notably low dark toxicity. In contrast, the parent and conjugates were found to be highly phototoxic, with impressive phototoxic indices (PIs) toward HPAC cell monolayers in particular, with PI values ranging from ∼580 to 760. Overall, our data indicate that the Ru(II) parent complex and its peptide conjugates show promise at both cell monolayers and 3D MCTS as photosensitizers for photodynamic therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:62 |
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| Enthalten in: |
Inorganic chemistry - 62(2023), 32 vom: 14. Aug., Seite 13089-13102 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Curley, Rhianne C [VerfasserIn] |
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| Links: |
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| Themen: |
7UI0TKC3U5 |
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| Anmerkungen: |
Date Completed 18.08.2023 Date Revised 18.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.inorgchem.3c01982 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM360356702 |
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| 520 | |a Tridentate ligand-coordinated ruthenium (II) polypyridyl complexes with large N-Ru-N bite angles have been shown to promote ligand field splitting and reduce singlet-triplet state mixing leading to dramatically extended emission quantum yields and lifetimes under ambient conditions. These effects are anticipated to enhance their photoinduced singlet oxygen production, promoting prospects for such complexes as type II phototherapeutics. In this contribution, we examined this putative effect for [Ru(bqp)(bqpCOOEt)]2+, Ru-bqp-ester, a heteroleptic complex containing bqp = [2,6-bi(quinolin-8-yl)pyridine], a well-established large bite angle tridentate ligand, as well as its peptide conjugates [Ru(bqp)(bqpCONH-ahx-FrFKFrFK(Ac)-CONH2)]5+ (Ru-bqp-MPP) and [Ru(bqp) (bqp)(CONH-ahx-RRRRRRRR-CONH2)]10+ (Ru-bqp-R8) that were prepared in an effort to promote live cell/tissue permeability and targeting of the parent. Membrane permeability of both parent and peptide conjugates were compared across 2D cell monolayers; A549, Chinese hamster ovary, human pancreatic cancer (HPAC), and 3D HPAC multicellular tumor spheroids (MCTS) using confocal microscopy. Both the parent complex and peptide conjugates showed exceptional permeability with rapid uptake in both 2D and 3D cell models but with little distinction in permeability or distribution in cells between the parent or peptide conjugates. Unexpectedly, the uptake was temperature independent and so attributed to passive permeation. Both dark and photo-toxicity of the Ru(II) complexes were assessed across cell types, and the parent showed notably low dark toxicity. In contrast, the parent and conjugates were found to be highly phototoxic, with impressive phototoxic indices (PIs) toward HPAC cell monolayers in particular, with PI values ranging from ∼580 to 760. Overall, our data indicate that the Ru(II) parent complex and its peptide conjugates show promise at both cell monolayers and 3D MCTS as photosensitizers for photodynamic therapy | ||
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| 700 | 1 | |a Noorani, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Walsh, Naomi |e verfasserin |4 aut | |
| 700 | 1 | |a Keyes, Tia E |e verfasserin |4 aut | |
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