Tripodal Quinone-Cyanine G-Quadruplex Ligands as Novel Photosensitizers on Photoinduced Cancer Cell Death

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• G-quadruplex (G4) DNA and RNA structures are implicated in various diseases.
• G4-selective photosensitizers are valuable for photodynamic therapy (PDT) but limited in variety.
• Tripodal quinone-cyanine dyes (tpQCys) were initially developed as G4 fluorescent probes.

Purpose of the Study:

• To evaluate the potential of novel tripodal quinone-cyanine dyes (tpQCys) as G4-selective photosensitizers for PDT.
• To investigate the cancer-selective apoptosis-inducing capabilities of tpQCys.
• To determine the mechanism of photoinduced cytotoxicity mediated by tpQCys.

Main Methods:

• Synthesis and characterization of tripodal quinone-cyanine dyes (tpQCys).
• Assessment of G4 selectivity and photoinduced cytotoxicity in cancer cells (HeLa).
• RNA sequencing (RNA-seq) analysis to identify molecular pathways, including apoptosis induction.

Main Results:

• The tpQCy skeleton demonstrates potential for developing G4-targeted photosensitizers.
• QCy(BnBT)3, a tpQCy derivative with high G4 selectivity, exhibited significant photoinduced cytotoxicity in HeLa cells.
• Direct oxidation of G4 structures is suggested to be critical for photoinduced cytotoxicity.
• RNA-seq confirmed that QCy(BnBT)3 treatment followed by photoirradiation clearly induced apoptosis.

Conclusions:

• Tripodal quinone-cyanine dyes are a promising scaffold for G4-targeted photosensitizers.
• QCy(BnBT)3 shows potential as a cancer-selective agent for photodynamic therapy.
• Targeting G4 structures with photosensitizers can effectively induce cancer cell apoptosis.