Activity-Based Photosensitizers with Optimized Triplet State Characteristics Toward Cancer Cell Selective and Image...

Area of Science:

• Medicinal Chemistry
• Photodynamic Therapy
• Cancer Theranostics

Background:

• Activity-based theranostic photosensitizers offer dual imaging and therapeutic benefits for cancer treatment.
• Limited availability of photosensitizer cores easily convertible to activity-based forms hinders progress.

Purpose of the Study:

• To develop novel photosensitizer (PS) cores based on the dicyanomethylene-4H-chromene (DCM) scaffold for activity-based theranostics.
• To investigate the impact of iodine incorporation and positioning on PS performance.
• To create a cysteine-activatable PS for targeted cancer therapy.

Main Methods:

• Modification of the DCM core with iodine atoms to synthesize DCM-I and I-DCM-Cl photosensitizers.
• Computational studies to evaluate singlet oxygen generation.
• In vitro cell culture studies to assess photocytotoxicity and fluorescence response.

Main Results:

• DCM-I demonstrated superior singlet oxygen generation and photodynamic efficacy compared to I-DCM-Cl.
• The DCM-I core proved to be a versatile scaffold for developing phototheranostic agents.
• A cysteine-activatable derivative (DCM-I-Cys) exhibited selective photocytotoxicity and fluorescence in cancer cells.

Conclusions:

• Iodine-modified DCM cores are effective for developing activity-based theranostic photosensitizers.
• The developed cysteine-activatable photosensitizer shows potential for targeted cancer therapy with enhanced imaging capabilities.