Moderately Heavy Atom-Substituted BODIPY Photosensitizer with Mitochondrial Targeting Ability for Imaging-Guided...

Area of Science:

• Biochemistry
• Organic Chemistry
• Medical Imaging

Background:

• Advanced photodynamic therapy (PDT) requires photosensitizers with multi-functional properties including targeting, diagnostics, and therapeutic capabilities.
• Triphenylphosphonium (TPP)-functionalized boron-dipyrromethene (BODIPY) dyes offer potential for developing such agents.

Purpose of the Study:

• To synthesize and characterize two TPP-functionalized BODIPY dyes, TPPB-H and TPPB-Br, with varying halogenation at the 6-position.
• To evaluate their photophysical properties, cellular uptake, mitochondrial targeting, and photocytotoxicity for potential application in imaging-guided PDT.

Main Methods:

• Synthesis of TPPB-H and TPPB-Br dyes.
• Photophysical characterization including singlet oxygen (¹O₂) and fluorescence quantum yield measurements.
• Confocal laser scanning microscopy for cellular uptake and mitochondrial targeting assessment in MCF-7 and HeLa cancer cells.
• Photocytotoxicity assays to determine half-maximal inhibitory concentrations (IC50).

Main Results:

• TPPB-Br exhibited a significantly enhanced ¹O₂ quantum yield (0.28) compared to TPPB-H (0.0059) due to the heavy-atom effect of bromine, with only a minor reduction in fluorescence quantum yield.
• Both dyes demonstrated high targeting specificity towards cancer cell mitochondria, attributed to TPP cation functionalization.
• TPPB-Br showed potent photocytotoxicity against MCF-7 (IC50 = 0.12 μM) and HeLa (IC50 = 0.77 μM) cells, while TPPB-H showed less pronounced effects.

Conclusions:

• The dibrominated BODIPY dye, TPPB-Br, effectively balances singlet oxygen production and fluorescence, demonstrating its potential as a theranostic agent.
• TPPB-Br's mitochondrial specificity and potent photocytotoxicity make it a promising candidate for imaging-guided photodynamic therapy.