Chiral RuII -PtII Complexes Inducing Telomere Dysfunction against Cisplatin-Resistant Cancer Cells.

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 RuII -PtII 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 RuII -PtII dinuclear complex as a G-quadruplex stabilizer with an anti-cancer effect towards drug-resistant tumors inside an animal model.

• Authors: Kai Xiong, Cheng Ouyang, Jiaqi Liu, Johannes Karges, Xinlin Lin, Xiang Chen, Yu Chen, Jian Wan, Liangnian Ji, Hui Chao
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 61 Issue 33 Pg. e202204866 (08 15 2022) ISSN: 1521-3773 [Electronic] Germany
• PMID: 35736788 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Wiley-VCH GmbH.

Chemical References

• Antineoplastic Agents
• Coordination Complexes
• Ruthenium
• DNA
• Telomerase
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Cisplatin (metabolism, pharmacology)
• Coordination Complexes (metabolism, pharmacology, therapeutic use)
• DNA
• G-Quadruplexes
• Mice
• Neoplasms
• Ruthenium (metabolism, pharmacology)
• Telomerase (genetics)
• Telomere