Exploring Structure-Activity Relationships in Photodynamic Therapy Anticancer Agents Based on Ir(III)-COUPY...

Area of Science:

• Chemistry
• Biomedical Engineering
• Oncology

Background:

• Photodynamic therapy (PDT) is a promising non-invasive treatment for drug-resistant cancers.
• Development of effective, non-toxic photosensitizers, especially for hypoxic conditions, is crucial.

Purpose of the Study:

• To design and synthesize novel PDT agents based on iridium(III)-COUPY conjugates.
• To explore structure-activity relationships influencing photophysical properties and anticancer efficacy.
• To evaluate the efficacy of these agents against cisplatin-resistant cancer cells under normoxic and hypoxic conditions.

Main Methods:

• Synthesis of iridium(III)-COUPY conjugates with structural modifications on the coumarin scaffold.
• Characterization of photophysical properties (e.g., phototoxicity, ROS generation).
• In vitro evaluation of cellular uptake and phototherapeutic efficacy in A2780cis cancer cells.

Main Results:

• Structural modifications of the coumarin scaffold significantly impacted photophysical properties and cellular uptake.
• All synthesized Ir(III)-COUPY conjugates demonstrated high phototoxicity under green light irradiation via reactive oxygen species (ROS) generation.
• Two lead conjugates exhibited significant phototherapeutic effects in cisplatin-resistant A2780cis cells, even under hypoxic conditions.

Conclusions:

• Ir(III)-COUPY conjugates are effective PDT agents with potent anticancer activity.
• These agents can overcome acquired cisplatin resistance in cancer cells.
• Conjugation of far-red/NIR-emitting COUPY dyes with transition metal complexes offers a viable strategy for advanced phototherapy.