Photodamaging of Mitochondrial DNA to Overcome Cisplatin Resistance by a RuII -PtII Bimetallic Complex
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Updated: Feb 4, 2026

Synthesis of Bimetallic Pt/Sn-based Nanoparticles in Ionic Liquids
Published on: August 23, 2018
Yue Zheng1, Dong-Yang Zhang1, Hang Zhang1
1MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, P. R. China.
Abstract:
Emerging studies have shown that mitochondrial DNA (mtDNA) is an attractive target for anticancer therapeutics. Herein, a heterobimetallic complex [Ru(dip)2 (μ-bpm)PtCl2 ]Cl2 (RuPt; dip=4,7-diphenyl-1,10-phenanthroline; bpm=2,2'-bipyrimidine) and the corresponding mononuclear complex [Ru(dip)2 (bpm)]Cl2 (Ru) have been designed and synthesized. RuPt can bind to mtDNA and damage it both in the dark and upon visible light irradiation. By using a variety of methods, it was demonstrated that RuPt can interfere with the function of mtDNA by decreasing the amplification and copy number of mtDNA, and affecting the transcriptional level of mitochondria-encoded genes. Furthermore, RuPt can disturb the physiological processes of mitochondria and induce caspase-dependent apoptosis in the presence of light. In addition, RuPt shows low systemic toxicity and potent in vivo anticancer potency upon light irradiation. This study provides strong evidence that mtDNA is an important molecular target of RuPt, and photodamaging mtDNA is an effective strategy to overcome cisplatin resistance.
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