Highly Selective Mitochondrial Targeting by a Ruthenium(II) Peptide Conjugate: Imaging and Photoinduced Damage of Mitochondrial DNA.

ABSTRACT

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.