Chiral Ru^II -Pt^II Complexes Inducing Telomere Dysfunction against Cisplatin-Resistant Cancer Cells

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.