Unveiling the interaction between PDT active squaraines with ctDNA: A spectroscopic study

Area of Science:

• Biochemistry
• Photochemistry
• Molecular Biology

Background:

• Squaraine dyes are investigated as photosensitizers for photodynamic therapy (PDT).
• Their efficacy in PDT relies on generating reactive oxygen species (ROS) and inducing DNA damage.
• Understanding squaraine-DNA interactions is critical for optimizing PDT strategies.

Purpose of the Study:

• To determine the binding mode between halogenated squaraines (Br-C4, I-C4) and calf thymus DNA (ctDNA).
• To evaluate the significance of squaraine-DNA interactions for their photosensitizing capabilities.

Main Methods:

• UV-Vis spectroscopy
• Fluorescence spectroscopy
• Iodide quenching studies
• Ionic strength assays
• Fluorescence Resonance Energy Transfer (FRET)

Main Results:

• Squaraines (Br-C4, I-C4) exhibit external binding to ctDNA.
• The binding mode was identified as minor groove binding.
• Squaraines displaced Hoechst, a known DNA groove binder, from ctDNA.
• Association and dissociation constants were determined and compared to known groove binders.

Conclusions:

• Halogenated squaraines interact with ctDNA via minor groove binding.
• This binding mechanism supports their potential application as photosensitizers in PDT.
• Further studies can leverage these findings to design more effective squaraine-based PDT agents.