Electrochemical Detection of a Novel Pt(IV) Prodrug with the Metronidazole Axial Ligand in the Hypoxic Area
Electrochemical Detection of a Novel Pt(IV) Prodrug with the Metronidazole Axial Ligand in the Hypoxic Area
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DOI：
10.1021/acs.inorgchem.2c02062
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发表时间：
2022-09-01
影响因子：
4.6
通讯作者：
Krasnovskaya, Olga O.
中科院分区：
文献类型：
--
作者：
Spector, Daniil, V;Erofeev, Alexander S.;Krasnovskaya, Olga O.
本文报道了一种在轴向位置具有甲硝唑的Pt（IV）前药Pt-Mnz。将硝基芳族轴向配体与顺铂支架缀合以在缺氧条件下不可逆地还原，从而将Pt（IV）前药保留在缺氧区域中。对干燥的药物预孵育的肿瘤细胞样品的X射线近边吸附光谱（XANES）显示顺铂从Pt-Mnz前药中逐渐释放，而不是快速的细胞内降解。前药渗透到三维（3D）球状体细胞培养物的能力进行了评估，通过一种新的电化学测定通过铂涂层的碳纳米电极，能够单细胞测量。在单个肿瘤球体中使用独特的电化学测量技术，我们能够检测轴向配体对缺氧的实时响应，并建立药物渗透到肿瘤模型中的深度。
We report herein a Pt(IV) prodrug with metroni-dazole 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.