A dual-targeted theranostic photosensitizer based on a TADF fluorescein derivative

Area of Science:

• Biomedical research
• Cancer therapy
• Theranostics

Background:

• Cancer diagnosis and therapy remain significant challenges.
• Photodynamic therapy (PDT) offers a novel approach but often lacks specific selectivity.
• Existing photosensitizers have limitations in targeting tumor markers and cellular compartments.

Purpose of the Study:

• To develop a dual-targeted theranostic photosensitizer for enhanced cancer diagnosis and treatment.
• To investigate the targeting capabilities of FL-RGD towards tumor tissues and lysosomes.
• To evaluate the efficacy of FL-RGD in photodynamic therapy and fluorescence imaging.

Main Methods:

• Covalent conjugation of a fluorescein derivative (FL) with tumor-targeting cyclic arginine-glycine-aspartic acid tripeptide (RGD).
• Utilizing FL's thermally activated delayed fluorescence (TADF) property for efficient PDT.
• Assessing diagnostic performance via fluorescence imaging in cells and tumor-bearing mice.
• Evaluating therapeutic efficacy using MTT assays, FACS analysis, and in vivo PDT experiments.

Main Results:

• FL-RGD demonstrated dual targeting of tumor tissues and lysosomes.
• Lysosomal damage via singlet oxygen (¹O₂) was identified as the mechanism for efficient PDT.
• Successful fluorescence imaging confirmed diagnostic capabilities in vitro and in vivo.
• MTT assays, FACS, and PDT experiments validated the therapeutic potential against tumors.

Conclusions:

• FL-RGD shows significant potential as a theranostic agent for specific cancer diagnosis and treatment.
• The dual-targeting strategy enhances selectivity and therapeutic efficacy.
• FL-RGD facilitates efficient photodynamic therapy through lysosome-targeted mechanisms.