Cellular localization of iron(II) polypyridyl complexes determines their anticancer action mechanisms

Biomaterials
Jingjing ChenTianfeng Chen

Abstract

Elucidation of relationship among cellular uptake, localization and biological activities of metal complexes could make great breakthrough in the understanding of their action mechanisms and provide useful information for rational design of metal-based anticancer drugs. Iron(II) complexes have emerged as potential anticancer drug candidates with application potential in cancer imaging and therapy. Herein, a series of iron(II) polypyridyl complexes with different lipophilicity were rationally designed, synthesized and identified as potent anticancer agents. The relationship between the cellular localization and molecular action mechanisms of the complexes was also elucidated. The results showed that, the increase in planarity of the Fe(II) polypyridyl complexes enhanced their lipophilicity and cellular uptake, leading to improved anticancer efficacy. The hydrophilic Fe(II) complex entered cancer cells through transferring receptor (TfR)-mediated endocytosis, and translocated to cell nucleus, where they induced S phase cell cycle arrest through triggering DNA damage-mediated p53 pathway. Interestingly, the hydrophobic Fe(II) complexes displayed higher anticancer efficacy than the hydrophilic ones, but shared the same uptake pathw...Continue Reading

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Citations

Nov 23, 2016·Future Medicinal Chemistry·Mickaël MarloyeFrançois Dufrasne
Aug 11, 2020·Dalton Transactions : an International Journal of Inorganic Chemistry·Mathilde BouchéPhilippe C Gros
Feb 25, 2017·Chemistry, an Asian Journal·Haoqiang LaiTianfeng Chen
Dec 21, 2017·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Jincan ChenLanmei Chen
Feb 7, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xueyang FangTianfeng Chen
Mar 9, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xiaoyu PanXiaoguang Liu
Nov 27, 2018·Journal of Agricultural and Food Chemistry·Qingyun TanTianfeng Chen

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