Reactive Oxygen Species Inducing Triazolylpyridine-Based Ru(II)/Ir(III) Complexes for Therapeutically Enhanced Triple-Negative Breast Cancer Treatment

The effectiveness of existing systemic and targeted therapies
remains
limited in triple-negative breast cancer (TNBC) treatment. Much research
has been conducted on reactive oxygen species (ROS)-mediated cancer
cell death to overcome the shortcomings of the currently applied chemotherapeutic
treatments. Herein, we have developed novel Ru(II)/Ir(III)-mediated
triazolylpyridine complexes as ROS inducers. Upon entering the TNBC
cells, the Ru(II) complex effectively accumulated in mitochondria
and triggered the creation of ROS, facilitating dysfunction of mitochondria
and oxidative DNA damage, ultimately causing death of cells through
G2/M phase cell cycle arrest. Eventually, this complex induced the
upregulation of BAX (pro-apoptotic protein) and downregulation of
BCL-2 (antiapoptotic protein) and triggered the caspase 3/9 pathway
and released cytochrome c in the cytosol for apoptosis.
The complex JRu (RuII triazolylpyridine) significantly
reduced the integrity and viability of TNBC 3D spheroids.