Acid-base properties of chlorin e6: relation to cellular uptake

Area of Science:

• Photodynamic therapy
• Biophysical chemistry
• Pharmacology

Background:

• Chlorin e6 exhibits high absorption in the red spectral region, making it suitable for photodynamic therapy.
• Understanding chlorin e6's behavior in physiological conditions is crucial for its therapeutic application.

Purpose of the Study:

• To investigate the influence of pH on the spectral properties and lipophilicity of chlorin e6.
• To examine the effect of fetal calf serum (FCS) on chlorin e6's behavior in varying pH conditions.
• To correlate these changes with cellular uptake and potential tumor selectivity.

Main Methods:

• Spectrophotometric and fluorimetric titrations of chlorin e6 in phosphate-buffered saline (PBS) with and without FCS.
• Measurement of partition coefficients in a 1-octanol-water system.
• Assessment of cellular uptake of chlorin e6 at different pH values in the presence of serum.

Main Results:

• pH variations altered chlorin e6's absorption and fluorescence spectra, with aggregate formation at low pH (<5).
• Fetal calf serum shifted the titration curve and induced spectral changes in protein-bound chlorin e6.
• Decreasing pH increased lipophilicity, and cellular uptake was higher at pH 6.7 compared to pH 7.3 and 7.6.

Conclusions:

• Changes in the surrounding medium's pH alter chlorin e6's lipophilicity.
• This pH-dependent lipophilicity influences serum protein binding and cell membrane interactions.
• These findings suggest a mechanism for selective tumor uptake of chlorin e6.