Dissecting the Interactions between Chlorin e6 and Human Serum Albumin

Area of Science:

• Biochemistry
• Photochemistry
• Biophysics

Background:

• Chlorin e6 (Ce6) is a widely used photosensitizer in photodynamic (PDT) and sonodynamic (SDT) therapies.
• Its clinical application is limited by poor water solubility and aggregation in physiological conditions, leading to reduced efficacy and unfavorable pharmacokinetics.

Purpose of the Study:

• To investigate the binding interaction between Ce6 and human serum albumin (HSA).
• To elucidate how HSA encapsulation affects Ce6's photophysical properties and reactive oxygen species (ROS) generation mechanisms for improved therapeutic outcomes.

Main Methods:

• Ensemble docking simulations were employed to identify Ce6 binding sites within HSA.
• Microsecond molecular dynamics simulations provided an atomistic description of the Ce6-HSA complex.
• Photophysical properties (absorption, emission, lifetime) and ROS production mechanisms were compared between free Ce6 and Ce6@HSA.

Main Results:

• Two primary binding pockets for Ce6 in HSA were identified: the Sudlow I site and the heme binding pocket.
• Ce6 encapsulation within HSA resulted in a spectral red-shift in both absorption and emission.
• The excited state lifetime of Ce6 increased, and a shift in ROS production mechanism from Type II to Type I was observed upon irradiation.

Conclusions:

• HSA encapsulation significantly enhances the water solubility and modifies the photophysical properties of Ce6.
• The altered photophysical and mechanistic properties of Ce6@HSA suggest improved potential for PDT and SDT applications.
• Understanding Ce6-HSA interactions provides a basis for designing more effective photosensitizers for clinical use.