Cell viability imaging in tumor spheroids via DNA binding of a ruthenium(II) light-switch complex

• Published in: Chemical communications (Cambridge, England) England), 2024-06, Vol.60 (49), p.6308-6311
• Main Authors: Ramu, Vadde, Wijaya, Lukas S, Beztsinna, Nataliia, Van de Griend, Corjan, van de Water, Bob, Bonnet, Sylvestre, Le Dévédec, Sylvia E
• Format: Article
• Language: English
• Subjects: Binding; Carcinogens; Cell Line, Tumor; Cell Survival - drug effects; Chemistry; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; DNA - chemistry; Dyes; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Humans; Light; Medical imaging; Optical Imaging; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Ruthenium - chemistry; Ruthenium compounds; Spheroids; Spheroids, Cellular - metabolism; Tumors
• ISSN: 1359-7345; 1364-548X; 1364-548X
• DOI: 10.1039/d4cc01425a

The famous ''light-switch'' ruthenium complex [Ru(bpy) (dppz)](PF ) (1) has been long known for its DNA binding properties . However, the biological utility of this compound has been hampered by its poor cellular uptake in living cells. Here we report a bioimaging application of 1 as cell viability probe in both 2D cells monolayer and 3D multi-cellular tumor spheroids of various human cancer cell lines (U87, HepG2, A549). When compared to propidium iodide, a routinely used cell viability probe, 1 was found to enhance the staining of dead cells in particular in tumor spheroids. 1 has high photostability, longer Stokes shift, and displays lower cytotoxicity compared to propidium iodide, which is a known carcinogenic. Finally, 1 was also found to displace the classical DNA binding dye Hoechst in dead cells, which makes it a promising dye for time-dependent imaging of dead cells in cell cultures, including multi-cellular tumor spheroids.