Mitochondrial-DNA-Targeted IrIII -Containing Metallohelices with Tunable Photodynamic Therapy Efficacy in Cancer Cells.
Xuezhao LiJinguo WuLei WangCheng HeLiyong ChenYang JiaoChun-Ying DuanPublished in: Angewandte Chemie (International ed. in English) (2020)
The development of DNA-targeted photodynamic therapy (PDT) agents for cancer treatment has drawn substantial attention. Herein, the design and synthesis of dinuclear IrIII -containing luminescent metallohelices with tunable PDT efficacy that target mitochondrial DNA in cancer cells are reported. The metallohelices are fabricated using dynamic imine-coupling chemistry between aldehyde end-capped fac-Ir(ppy)3 handles and linear alkanediamine spacers, followed by reduction of the imine linkages. The length and odd-even character of the diamine alkyl linker determined the stereochemistry (helicates vs. mesocates). Compared to the helicates, the mesocates exhibit improved apoptosis-induction upon white-light irradiation. Molecular docking studies indicate that the mesocate with a proper length of diamine spacers shows stronger affinity for the minor groove of DNA. This study highlights the potential of DNA-targeting IrIII -containing metallohelices as PDT agents.
Keyphrases
- photodynamic therapy
- mitochondrial dna
- copy number
- molecular docking
- circulating tumor
- fluorescence imaging
- cell free
- cancer therapy
- single molecule
- oxidative stress
- molecular dynamics simulations
- nucleic acid
- energy transfer
- quantum dots
- drug delivery
- cell death
- genome wide
- radiation therapy
- dna methylation
- drug discovery
- human health
- case control
- visible light