A Novel Substituted Benzo[g]quinoxaline-Based Cyclometalated Ru(II) Complex as a Biocompatible Membrane-Targeted PDT...

Area of Science:

• Inorganic Chemistry
• Materials Science
• Cancer Research

Background:

• Ruthenium(II) complexes are investigated for their potential anticancer properties.
• Photodynamic therapy (PDT) offers a targeted approach to cancer treatment.
• Developing novel photosensitizers is crucial for enhancing PDT efficacy.

Purpose of the Study:

• To synthesize and characterize three novel ruthenium(II) complexes, RuL1-RuL3.
• To evaluate the phototoxicity of these complexes against various human cancer cell lines.
• To elucidate the mechanism of action for the most potent complex, RuL2.

Main Methods:

• Synthesis of octahedral ruthenium(II) complexes with cyclometalating benzo[g]quinoxaline ligands.
• In vitro phototoxicity assays on cervical, melanoma, and colon cancer cells.
• Cellular uptake studies, lipid peroxidation assays, and apoptosis pathway analysis.

Main Results:

• Compounds RuL1-RuL3 demonstrated significant phototoxicity upon blue light irradiation.
• Complex RuL2 exhibited a phototoxicity index of 100 in HCT116 colon cancer cells.
• RuL2 localized in cellular membranes, induced lipid peroxidation and ROS generation, activating caspase 3 and apoptosis.
• RuL2 showed efficacy against colon cancer stem cells, a notoriously difficult-to-treat population.

Conclusions:

• Ruthenium(II) complexes, particularly RuL2, are potent photosensitizers for cancer therapy.
• Membrane-localized photodynamic therapy mediated by RuL2 offers a novel strategy against cancer.
• RuL2 represents a promising therapeutic agent for targeting colon cancer stem cells and preventing recurrence.