Lysosome-targeted Ru(II)-cyclopentadienyl organometallic anticancer complexes.

Area of Science:

• Organometallic Chemistry
• Medicinal Chemistry
• Cancer Biology

Background:

• Cancer remains a major global health challenge, driving research into new treatments.
• Ruthenium complexes offer potential advantages over traditional platinum drugs.
• Fluorescent organometallic compounds are being explored for targeted cancer therapy.

Purpose of the Study:

• Synthesize and characterize novel fluorescent Ruthenium(II)-cyclopentadienyl organometallic complexes.
• Evaluate the cytotoxicity and cellular uptake of these complexes in various cancer cell lines.
• Investigate the mechanism of action, including cellular targeting and induction of cell death.

Main Methods:

• Synthesis and structural characterization (NMR, FTIR, UV-Vis, X-ray crystallography).
• Cytotoxicity assays on 4T1, CT26, U2OS, and 3T3 cell lines.
• Confocal microscopy for cellular uptake and localization studies.
• Mechanistic studies on oxidative stress and apoptosis induction.

Main Results:

• Novel fluorescent Ru(II) complexes ([Ru(η⁵-C₅H₅)(NN)(Ph₂P-CH₂-pip-NBD)][PF₆]) were successfully synthesized and characterized.
• Complexes 1, 3, and 5 demonstrated significant cytotoxicity, especially against U2OS human osteosarcoma cells.
• Efficient cellular internalization via caveolin-mediated endocytosis and lysosomal accumulation were observed.
• Mechanism involves ROS generation, oxidative stress, and apoptosis induction, with lysosomal targeting.

Conclusions:

• The synthesized Ru(II) complexes exhibit potent anticancer activity and favorable stability.
• Lysosomal tropism, facilitated by the NBD fluorophore, is a key feature for targeted delivery.
• These complexes represent promising candidates for developing novel, effective, and traceable anticancer agents.