A Cancer Cell-Selective and Low-Toxic Bifunctional
Heterodinuclear Pt(IV)–Ru(II) Anticancer Prodrug
Posted on 2018-02-13 - 12:48
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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Ma, Lili; Lin, Xudong; Li, Cai; Xu, Zoufeng; Chan, Chun-Yin; Tse, Man-Kit; et al. (2018). A Cancer Cell-Selective and Low-Toxic Bifunctional
Heterodinuclear Pt(IV)–Ru(II) Anticancer Prodrug. ACS Publications. Collection. https://doi.org/10.1021/acs.inorgchem.8b00053
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AUTHORS (8)
LM
Lili Ma
XL
Xudong Lin
CL
Cai Li
ZX
Zoufeng Xu
CC
Chun-Yin Chan
MT
Man-Kit Tse
PS
Peng Shi
GZ
Guangyu Zhu