Adams Casey J, Meade Thomas J
Departments of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University Evanston Illinois 60208 USA
Chem Sci. 2020 Jan 28;11(9):2524-2530. doi: 10.1039/c9sc05937g.
Pt(iv) prodrugs have emerged as versatile therapeutics for addressing issues regarding off-target toxicity and the chemoresistance of classic Pt(ii) drugs such as cisplatin and carboplatin. There is significant potential for Pt(iv) complexes to be used as theranostic agents, yet there are currently no reported examples of Gd(iii)-Pt(iv) agents for simultaneous MR imaging and chemotherapy. Here we report the synthesis, characterization, and efficacy of two Gd(iii)-Pt(iv) agents, and . Both agents are water soluble and stable under extracellularly relevant conditions but are reduced under intracellular conditions. Both are cytotoxic in multiple cancer cell lines, cell permeable, and significantly enhance the -weighted MR contrast of multiple cell lines. Thus, and are promising agents for tandem MR imaging and chemotherapy and provide a versatile platform through which future Gd(iii)-Pt(iv) agents can be developed.
铂（IV）前药已成为解决脱靶毒性和经典铂（II）药物（如顺铂和卡铂）化疗耐药性问题的多功能治疗药物。铂（IV）配合物作为诊疗剂具有巨大潜力，但目前尚无用于同时进行磁共振成像和化疗的钆（III）-铂（IV）试剂的报道。在此，我们报告了两种钆（III）-铂（IV）试剂的合成、表征及疗效。两种试剂均具有水溶性，在细胞外相关条件下稳定，但在细胞内条件下会被还原。二者在多种癌细胞系中均具有细胞毒性，具有细胞渗透性，并能显著增强多种细胞系的T1加权磁共振对比度。因此，这两种试剂有望用于串联磁共振成像和化疗，并提供一个通用平台，未来可据此开发钆（III）-铂（IV）试剂。
