Luminescent ruthenium complexes for theranostic applications

Area of Science:

• Coordination Chemistry
• Bioinorganic Chemistry
• Photochemistry

Background:

• Development of novel luminescent metal complexes for biomedical applications.
• Ruthenium complexes are explored for their cytotoxic and photophysical properties.

Purpose of the Study:

• Synthesize and characterize water-soluble, luminescent ruthenium(II) complexes.
• Investigate the interaction of cis-[Ru(phen)2(ImH)2](2+) with human serum albumin.
• Evaluate the cellular uptake, cytotoxicity, and mechanism of action of cis-[Ru(phen)2(ImH)2](2+) in cancer cells.

Main Methods:

• Synthesis and spectroscopic characterization (NMR, CD) of ruthenium complexes.
• Isothermal titration calorimetry to study protein-ligand interactions.
• Luminescent confocal microscopy for cellular uptake studies.
• Cytotoxicity assays (IC50), flow cytometry, and western blot for mechanism of action.

Main Results:

• Water-soluble luminescent cis-[Ru(L-L)2(L)2](2+) complexes were successfully synthesized.
• cis-[Ru(phen)2(ImH)2](2+) binds to human serum albumin via noncovalent interactions (Kb = 9.8 × 10^4 M^-1 L).
• High cellular uptake and potent cytotoxicity (IC50 = 0.1 μmol L^-1) of cis-[Ru(phen)2(ImH)2](2+) in HCT116 cells.
• The complex induces G1 cell cycle arrest and activates PARP in p53(-/-) cells, suggesting a cytostatic mechanism.

Conclusions:

• cis-[Ru(phen)2(ImH)2](2+) is a promising luminescent ruthenium complex with significant cytotoxic potential.
• The complex exhibits selective interaction with proteins and efficient cellular uptake.
• The findings suggest a cytostatic mechanism involving cell cycle arrest and apoptosis induction, warranting further investigation for cancer therapy.