Insights into the binding mechanism of BODIPY-based photosensitizers to human serum albumin: A combined experimental and computational study.

Photodynamic therapy (PDT) is a noninvasive and effective approach in clinical cancer treatments. Boron-dipyrromethene (BODIPY)-based derivatives have emerged as novel and promising photosensitizers (PSs) in PDT, attributed to their strong near-infrared singlet oxygen luminescence emissions and high photostabilities. However, the binding mechanism of BODIPY derivatives to proteins, key for their therapeutic and biomedical applications is still poorly understood. Here, we investigated the molecular interactions of two 2, 6-diiodo-BODIPY derivatives with human serum albumin (HSA) using combined experimental and computational techniques. Our spectroscopic results showed that both BODIPY derivatives formed stable complexes with HSA. Strikingly, the BODIPY/HSA complexes exhibited notably enhanced water solubility and singlet oxygen generation efficiency with respect to the BODIPY alone. Furthermore, molecular docking, molecular dynamics simulations, and binding free energy calculations provided the structural and energetic insights into the binding mechanism of BODIPY-based derivatives to HSA. Our work demonstrated that conjugation of BODIPYs with HSA may be a promising strategy to enhance the performance of BODIPY-based PSs, and the combination of computational and experimental techniques is expected to play key roles in the design and development of novel PSs with improved bioavailability and biocompatibility for cancer therapeutic applications.