Chemistry Department, Lomonosov Moscow State University, Leninskie gory 1,3, Moscow 119991, Russia.
National University of Science and Technology (MISIS), Leninskiy prospect 4, Moscow 119049, Russia.
Inorg Chem. 2022 Sep 19;61(37):14705-14717. doi: 10.1021/acs.inorgchem.2c02062. Epub 2022 Sep 1.
We report herein a Pt(IV) prodrug with metronidazole in axial positions -. 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 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.
我们在此报告了一种顺铂结构的米托硝唑前药 - 。硝基芳环轴向配体与顺铂支架连接，在缺氧条件下不可逆还原，从而将顺铂前药保留在缺氧区域。对干燥药物预孵育肿瘤细胞样品的 X 射线近边吸收光谱（XANES）分析表明，顺铂从前药中逐渐释放，而不是快速的细胞内降解。通过使用涂有铂的碳纳米电极的新型电化学测定法评估前药穿透三维（3D）球体细胞培养物的能力，该测定法能够进行单细胞测量。使用电化学测量在单个肿瘤球体中的独特技术，我们不仅能够实时检测轴向配体对缺氧的反应，还能够确定药物进入肿瘤模型的深度。
