Electrochemical Detection of a Novel Pt(IV) Prodrug with the Metronidazole Axial Ligand in the Hypoxic Area

We report herein a Pt­(IV) prodrug with metronidazole in axial positions Pt-Mnz. The nitroaromatic axial ligand was conjugated with a cisplatin scaffold to irreversibly reduce under hypoxic conditions, thereby retaining the Pt­(IV) prodrug in the area of hypoxia. X-ray near-edge adsorption spectrosc...

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Published inInorganic chemistry Vol. 61; no. 37; pp. 14705 - 14717
Main Authors Spector, Daniil V., Erofeev, Alexander S., Gorelkin, Petr V., Vaneev, Alexander N., Akasov, Roman A., Ul’yanovskiy, Nikolay V., Nikitina, Vita N., Semkina, Alevtina S., Vlasova, Kseniya Yu, Soldatov, Mikhail A., Trigub, Alexander L., Skvortsov, Dmitry A., Finko, Alexander V., Zyk, Nikolay V., Sakharov, Dmitry A., Majouga, Alexander G., Beloglazkina, Elena K., Krasnovskaya, Olga O.
Format Journal Article
LanguageEnglish
Published American Chemical Society 19.09.2022
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Abstract We report herein a Pt­(IV) prodrug with metronidazole in axial positions Pt-Mnz. The nitroaromatic axial ligand was conjugated with a cisplatin scaffold to irreversibly reduce under hypoxic conditions, thereby retaining the Pt­(IV) prodrug in the area of hypoxia. X-ray near-edge adsorption spectroscopy (XANES) on dried drug-preincubated tumor cell samples revealed a gradual release of cisplatin from the Pt-Mnz prodrug instead of rapid intracellular degradation. The ability of the prodrug to penetrate into three-dimensional (3D) spheroid cellular cultures was evaluated by a novel electrochemical assay via a platinum-coated carbon nanoelectrode, capable of single-cell measurements. Using a unique technique of electrochemical measurements in single tumor spheroids, we were able to both detect the real-time response of the axial ligand to hypoxia and establish the depth of penetration of the drug into the tumor model.
AbstractList We report herein a Pt­(IV) prodrug with metronidazole in axial positions Pt-Mnz. The nitroaromatic axial ligand was conjugated with a cisplatin scaffold to irreversibly reduce under hypoxic conditions, thereby retaining the Pt­(IV) prodrug in the area of hypoxia. X-ray near-edge adsorption spectroscopy (XANES) on dried drug-preincubated tumor cell samples revealed a gradual release of cisplatin from the Pt-Mnz prodrug instead of rapid intracellular degradation. The ability of the prodrug to penetrate into three-dimensional (3D) spheroid cellular cultures was evaluated by a novel electrochemical assay via a platinum-coated carbon nanoelectrode, capable of single-cell measurements. Using a unique technique of electrochemical measurements in single tumor spheroids, we were able to both detect the real-time response of the axial ligand to hypoxia and establish the depth of penetration of the drug into the tumor model.
We report herein a Pt(IV) prodrug with metronidazole in axial positions Pt-Mnz. The nitroaromatic axial ligand was conjugated with a cisplatin scaffold to irreversibly reduce under hypoxic conditions, thereby retaining the Pt(IV) prodrug in the area of hypoxia. X-ray near-edge adsorption spectroscopy (XANES) on dried drug-preincubated tumor cell samples revealed a gradual release of cisplatin from the Pt-Mnz prodrug instead of rapid intracellular degradation. The ability of the prodrug to penetrate into three-dimensional (3D) spheroid cellular cultures was evaluated by a novel electrochemical assay via a platinum-coated carbon nanoelectrode, capable of single-cell measurements. Using a unique technique of electrochemical measurements in single tumor spheroids, we were able to both detect the real-time response of the axial ligand to hypoxia and establish the depth of penetration of the drug into the tumor model.We report herein a Pt(IV) prodrug with metronidazole in axial positions Pt-Mnz. The nitroaromatic axial ligand was conjugated with a cisplatin scaffold to irreversibly reduce under hypoxic conditions, thereby retaining the Pt(IV) prodrug in the area of hypoxia. X-ray near-edge adsorption spectroscopy (XANES) on dried drug-preincubated tumor cell samples revealed a gradual release of cisplatin from the Pt-Mnz prodrug instead of rapid intracellular degradation. The ability of the prodrug to penetrate into three-dimensional (3D) spheroid cellular cultures was evaluated by a novel electrochemical assay via a platinum-coated carbon nanoelectrode, capable of single-cell measurements. Using a unique technique of electrochemical measurements in single tumor spheroids, we were able to both detect the real-time response of the axial ligand to hypoxia and establish the depth of penetration of the drug into the tumor model.
Author Zyk, Nikolay V.
Trigub, Alexander L.
Skvortsov, Dmitry A.
Akasov, Roman A.
Soldatov, Mikhail A.
Ul’yanovskiy, Nikolay V.
Semkina, Alevtina S.
Majouga, Alexander G.
Krasnovskaya, Olga O.
Erofeev, Alexander S.
Gorelkin, Petr V.
Spector, Daniil V.
Sakharov, Dmitry A.
Vlasova, Kseniya Yu
Beloglazkina, Elena K.
Nikitina, Vita N.
Vaneev, Alexander N.
Finko, Alexander V.
AuthorAffiliation Federal Scientific Research Center “Crystallography and Photonics” Russian Academy of Sciences
Chemistry Department
Serbsky National Medical Research Center for Psychiatry and Narcology
The Smart Materials Research Institute Southern Federal University Sladkova
I.M. Sechenov First Moscow State Medical University
Core Facility Center “Arktika,” Northern (Arctic) Federal University
National Research Center “Kurchatov Institute”
National University of Science and Technology (MISIS)
Department of Basic and Applied Neurobiology
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Snippet We report herein a Pt­(IV) prodrug with metronidazole in axial positions Pt-Mnz. The nitroaromatic axial ligand was conjugated with a cisplatin scaffold to...
We report herein a Pt(IV) prodrug with metronidazole in axial positions Pt-Mnz. The nitroaromatic axial ligand was conjugated with a cisplatin scaffold to...
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Title Electrochemical Detection of a Novel Pt(IV) Prodrug with the Metronidazole Axial Ligand in the Hypoxic Area
URI http://dx.doi.org/10.1021/acs.inorgchem.2c02062
https://www.proquest.com/docview/2709017100
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