Gd(iii)-Pt(iv) theranostic contrast agents for tandem MR imaging and chemotherapy.
Gd(iii)-Pt(iv) theranostic contrast agents for tandem MR imaging and chemotherapy.
复制标题
DOI：
10.1039/c9sc05937g
复制
发表时间：
2020-01-28
期刊：
影响因子：
8.4
通讯作者：
Meade TJ
中科院分区：
文献类型：
--
作者：
Adams CJ;Meade TJ
PT(IV)前药已成为解决靶外毒性和经典铂(II)药物(如顺铂和卡铂)耐药问题的通用疗法。铂(IV)络合物有很大的潜力被用作治疗药物，但目前还没有报道Gd(III)-铂(IV)试剂同时用于磁共振成像和化疗的例子。本文报道了两种Gd(III)-铂(IV)试剂GP1和GP2的合成、表征和体外药效。这两种试剂在细胞外相关条件下都是水溶性和稳定的，但在细胞内条件下会被还原。两者在多种癌细胞系中都具有细胞毒性、细胞渗透性，并显著增强了多种癌细胞系的T1加权MR对比度。因此，GP1和GP2是很有希望用于串联磁共振成像和化疗的试剂，并提供了一个通用的平台，通过这个平台可以开发未来的Gd(III)-PT(IV)试剂。第一个例子是Gd(III)-Pt(IV)化疗药物，它被细胞内还原以在同时进行铂(II)化疗的同时提供MR对比剂增强。
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 in vitro efficacy of two Gd(iii)–Pt(iv) agents, GP1 and GP2. 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 T1-weighted MR contrast of multiple cell lines. Thus, GP1 and GP2 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. The first example of Gd(iii)–Pt(iv) theranostic agents that are intracellularly reduced to provide MR contrast enhancement with simultaneous Pt(ii) chemotherapy.
登录
查看更多内容
影响因子：
10.8
作者：
Holbrook, Robert J.;Rammohan, Nikhil;Rotz, Matthew W.;MacRenaris, Keith W.;Preslar, Adam T.;Meade, Thomas J.
通讯作者：
Meade, Thomas J.
影响因子：
15
作者：
Li, Hao;Meade, Thomas J.
通讯作者：
Meade, Thomas J.
影响因子：
3.8
作者：
Li X;Liu Y;Tian H
通讯作者：
Tian H
一种基于顺铂的铂 (IV) 前药，含有谷胱甘肽 S-转移酶抑制剂，可逆转非小细胞肺癌的顺铂耐药性
影响因子：
3.9
作者：
Chen, Hong;Wang, Xinyi;Gou, Shaohua
通讯作者：
Gou, Shaohua
影响因子：
3
作者：
Hall, MD;Dillon, CT;Hambley, TW
通讯作者：
Hambley, TW