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Targeting Photoinduced DNA Destruction by Ru(II) Tetraazaphenanthrene in Live Cells by Signal Peptide.

Authors
  • Burke, Christopher S1
  • Byrne, Aisling1
  • Keyes, Tia E1
  • 1 School of Chemical Sciences and National Centre for Sensor Research , Dublin City University , Glasnevin , Dublin 9 , Ireland. , (Ireland)
Type
Published Article
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Publication Date
Jun 06, 2018
Volume
140
Issue
22
Pages
6945–6955
Identifiers
DOI: 10.1021/jacs.8b02711
PMID: 29767962
Source
Medline
License
Unknown

Abstract

Exploiting NF-κB transcription factor peptide conjugation, a Ru(II)-bis-tap complex (tap = 1,4,5,8-tetraazaphenanthrene) was targeted specifically to the nuclei of live HeLa and CHO cells for the first time. DNA binding of the complex within the nucleus of live cells was evident from gradual extinction of the metal complex luminescence after it had crossed the nuclear envelope, attributed to guanine quenching of the ruthenium emission via photoinduced electron transfer. Resonance Raman imaging confirmed that the complex remained in the nucleus after emission is extinguished. In the dark and under imaging conditions the cells remain viable, but efficient cellular destruction was induced with precise spatiotemporal control by applying higher irradiation intensities to selected cells. Solution studies indicate that the peptide conjugated complex associates strongly with calf thymus DNA ex-cellulo and gel electrophoresis confirmed that the peptide conjugate is capable of singlet oxygen independent photodamage to plasmid DNA. This indicates that the observed efficient cellular destruction likely operates via direct DNA oxidation by photoinduced electron transfer between guanine and the precision targeted Ru(II)-tap probe. The discrete targeting of polyazaaromatic complexes to the cell nucleus and confirmation that they are photocytotoxic after nuclear delivery is an important step toward their application in cellular phototherapy.

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