Chiral Ru<sup>II</sup>‐Pt<sup>II</sup>Complexes Inducing Telomere Dysfunction against Cisplatin‐Resistant Cancer Cells
Kai Xiong, Cheng Ouyang, Jiaqi Liu, Johannes Karges, Xinlin Lin, Xiang Chen, Yu Chen, Jian Wan, Liang‐Nian Ji, Hui Chao
Abstract
Abstract The application of G‐quadruplex stabilizers presents a promising anticancer strategy. However, the molecular crowding conditions within cells diminish the potency of current G‐quadruplex stabilizers. Herein, chiral Ru II ‐Pt II dinuclear complexes were developed as highly potent G‐quadruplex stabilizers even under challenging molecular crowding conditions. The compounds were encapsulated with biotin‐functionalized DNA cages to enhance sub‐cellular localization and provide cancer selectivity. The nanoparticles were able to efficiently inhibit the endogenous activities of telomerase in cisplatin‐resistant cancer cells and cause cell death by apoptosis. The nanomaterials demonstrated high antitumor activity towards cisplatin‐resistant tumor cells as well as tumor‐bearing mice. To the best of our knowledge, this study presents the first example of a Ru II ‐Pt II dinuclear complex as a G‐quadruplex stabilizer with an anti‐cancer effect towards drug‐resistant tumors inside an animal model.