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Dose and time-dependent tolerability and efficacy of organo-osmium complex FY26 and its tissue pharmacokinetics in hepatocarcinoma-bearing mice
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Kumar, Swati, Needham, Russell J., Abraham, Kristin, Bridgewater, Hannah E., Garbutt, Lauren A, Xandri-Monje, Helena, Dallmann, Robert, Perrier, Sébastien, Sadler, Peter J. and Lévi, Francis A. (2021) Dose and time-dependent tolerability and efficacy of organo-osmium complex FY26 and its tissue pharmacokinetics in hepatocarcinoma-bearing mice. Metallomics, 13 (2). mfaa003. doi:10.1093/mtomcs/mfaa003 ISSN 1756-5901.
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WRAP-dose-time-dependent-tolerability-efficacy-organo-osmium-FY26-tissue-pharmacokinetics-hepatocarcinoma-mice-Dallmann-2020.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2206Kb) | Preview |
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WRAP-dose-time-dependent-tolerability-efficacy-organo-osmium-complex-FY26-tissue-pharmacokinetics-hepatocarcinoma-bearing-mice-Dallmann-2020.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (2047Kb) |
Official URL: https://doi.org/10.1093/mtomcs/mfaa003
Abstract
The organo-osmium complex [OsII(ɳ6-p-cym)(PhAzPy-NMe2)I]+ (FY26) exhibits promising in vitro antitumour activity against mouse hepatocarcinoma Hepa1-6 and other mouse or human cancer cell lines. Here, we drastically enhance water solubility of FY26 through the replacement of the PF6-counter-anion with chloride using a novel synthesis method. FY26.PF6 and FY26.Cl displayed similar in vitro cytoxicity in two cancer cell models. We then show the moderate and late anticancer efficacy of FY26.PF6 and FY26.Cl in a subcutaneous murine hepatocarcinoma mouse model. Both efficacy and tolerability varied according to FY26 circadian dosing time in hepatocarcinoma tumour-bearing mice. Tumour and liver uptake of the drug were determined over 48 h following FY26.Cl administration at Zeitgeber 6 (ZT6), when the drug is least toxic (in the middle of the light span when mice are resting). Our studies suggest the need to administer protracted low doses of FY26 at ZT6 in order to optimize its delivery schedule, for example through the use of chrono-releasing nanoparticles.
| Item Type: | Journal Article | ||||||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Metallomics | ||||||||
| Publisher: | Royal Society of Chemistry | ||||||||
| ISSN: | 1756-5901 | ||||||||
| Official Date: | February 2021 | ||||||||
| Dates: |
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| Volume: | 13 | ||||||||
| Number: | 2 | ||||||||
| Article Number: | mfaa003 | ||||||||
| DOI: | 10.1093/mtomcs/mfaa003 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Date of first compliant deposit: | 4 December 2020 | ||||||||
| Date of first compliant Open Access: | 22 December 2020 | ||||||||
| Related URLs: |
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