化学
顺铂
前药
癌细胞
细胞毒性
体内
转移
癌症研究
癌症
药理学
体外
生物化学
化疗
内科学
生物
医学
生物技术
作者
Lili Ma,Xudong Lin,Li Cai,Zoufeng Xu,Chun‐Yin Chan,Man‐Kit Tse,Peng Shi,Guangyu Zhu
出处
期刊:Inorganic Chemistry
[American Chemical Society]
日期:2018-02-13
卷期号:57 (5): 2917-2924
被引量:50
标识
DOI:10.1021/acs.inorgchem.8b00053
摘要
Although different types of metal-based anticancer complexes have been synthesized, novel complexes to reduce the serious side effect of cisplatin and conquer cancer metastasis are still highly desired. Here, we report the synthesis, characterization, and biological activity of a novel heterodinuclear Pt(IV)–Ru(II) anticancer prodrug. The Pt(IV)–Ru(II) complex exhibits good stability in both water and PBS solution. Biological evaluation revealed that this bifunctional Pt(IV)–Ru(II) complex utilizes the advantages of two metal centers to have both cytotoxicity and antimetastatic property as designed. Although the complex has comparable cytotoxicities to cisplatin in tested cancer cell lines, this prodrug selectively kills cancer but not normal cells, and the IC50 values of the Pt(IV)–Ru(II) complex are 7–10 times higher than those of cisplatin toward normal cells. The cancer cell selectivity is further demonstrated by a cancer–normal cell coculture system. In addition, the antimetastatic properties of the heterodinuclear complex are assessed by using highly metastatic human breast cancer cells, and the results show that the migration and invasion of cancer cells are effectively restrained after the treatment. Moreover, the Pt(IV)–Ru(II) complex displays lower toxicity than cisplatin in developing zebrafish embryos. We, therefore, report an example of heterodinuclear Pt(IV)–Ru(II) complex not only to defeat both drug resistance and cancer metastasis but also having significantly improved cancer cell selectivity and reduced in vivo toxicity than cisplatin.
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