Detailed Biological Profiling of a Photoactivated and Apoptosis Inducing pdppz Ruthenium(II) Polypyridyl Complex in Cancer Cells

Ruthenium
polypyridyl complexes show great promise as new photodynamic
therapy (PDT) agents. However, a lack of detailed understanding of
their mode of action in cells poses a challenge to their development.
We have designed a new Ru­(II) PDT candidate that efficiently enters
cells by incorporation of the lipophilic aromatic pdppz ([2,3-h]­dipyrido­[3,2-a:2′,3′-c]­phenazine) ligand and exhibits photoactivity through incorporation
of 1,4,5,8-tetraazaphenanthrene ancillary ligands. Its photoreactivity
toward biomolecules was studied in vitro, where light activation caused DNA cleavage. Cellular internalization
occurred via an energy dependent mechanism. Confocal and transmission
electron microscopy revealed that the complex localizes in various
organelles, including the mitochondria. The complex is nontoxic in
the dark, with cellular clearance within 96 h; however, upon visible
light activation it induces caspase-dependent and reactive-oxygen-species-dependent
apoptosis, with low micromolar IC50 values. This investigation
greatly increases our understanding of such systems in cellulo, aiding
development and realization of their application in cancer therapy.