Sun Yat-Sen University, China
Biomolecule/Organelle-Targeted Anti-Tumor Metal Complexes
Cisplatin and its successive analogues mainly exert their activities by causing DNA damage and induce apoptosis in cancer cells. With the development of molecular oncology, biomolecule- targeted anticancer strategies have become the mainstream in the search of new cancer drugs. At the biomolecular level, G-quadruplexes (G4s), histone deacetylases (HDACs), cyclin-dependent kinases (CDKs), and the mammalian target of rapamycin (mTOR) have drawn attention as promising anti-cancer targets. We have developed a series of self-assembled Pt(II) complexes, acting as selective and effective human telomeric G-4 binders and stabilizing certain G4s conformations. These Pt(II) complexes exhibit significant telomerase inhibition activity and higher anti-tumor efficacy than cisplatin. We have also focused on the rational design of non-platinum metal complexes acting as enzyme inhibitors, investigated their anti-cancer mechanisms in details and their capability to induce cancer cells apoptosis, para apoptosis, autophagy and cell cycle arrest. Recently, we have a lot of interest in the organelle-targeted multifunctional metallo-anticancer agents. The organelle targets that we investigate mainly include mitochondria, lysosome and nucleus. These metallo-anticaner agents possess excellent phosphorescent properties, allowing the real-time tracking of the morphological, behavioral, and micro-environmental changes in the organelles at the same time as treatment and exhibiting great theranostic potential. To further improve the therapeutic efficacy of metallodrugs, design and development of nanostructured materials is a promising strategy, in which the nanostructure is fabricated by metal complex directed self-assembly or simply functionalized with metallodrugs as anti-cancer agents, thus realizing multimode synergetic therapy. The anticancer properties and the theranostic potential of these nanomaterials and their in vivo anticancer properties have been explored in details for further biomedical applications.
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