Highly Selective Mitochondrial Targeting by a Ruthenium(II) Peptide Conjugate: Imaging and Photoinduced Damage of Mitochondrial DNA.
Christopher S BurkeAisling ByrneTia E KeyesPublished in: Angewandte Chemie (International ed. in English) (2018)
Mitochondrial DNA (mtDNA) plays a crucial but incompletely understood role in cellular biochemistry and etiology of numerous disease states. Thus, there is an urgent need for targeted probes that can dynamically respond to changes to mtDNA such as copy number in live cells, but it is difficult to permeate the mitochondrial membrane of the living cell. Now, a ruthenium(II) light-switching probe targeted by peptide vectorization selectively to mitochondrial nucleoids is presented. Evidence for DNA binding by the probe in live cells is derived from confocal fluorescence microscopy, resonance Raman, and luminescence lifetime imaging. While viable under imaging conditions, specific staining of mitochondrial DNA permitted efficient and selective photoinduced toxicity on a cell-by-cell basis under higher excitation intensities. This powerful combination of imaging and photocytotoxicity is an important step towards realizing phototheranostic application of such RuII probes.
Keyphrases
- mitochondrial dna
- copy number
- high resolution
- oxidative stress
- cancer therapy
- induced apoptosis
- dna binding
- single molecule
- genome wide
- single cell
- energy transfer
- dna methylation
- fluorescence imaging
- living cells
- small molecule
- cell therapy
- quantum dots
- optical coherence tomography
- transcription factor
- cell cycle arrest
- gene expression
- mesenchymal stem cells
- stem cells
- cell proliferation
- high throughput
- drug delivery
- fluorescent probe
- flow cytometry