Interaction between a water-soluble anionic porphyrin and human serum albumin unexpectedly stimulates the aggregation of the photosensitizer at the surface of the albumin

The 5,10,15,20-tetrakis(2,6-difluoro-3-sulfophenyl)porphyrin (TDFPPS ) was reported as a potential photosensitizer for photodynamic therapy. The capacity of the photosensitizers to be carried in the human bloodstream is predominantly determined by its extension of binding, binding location, and binding mechanism to human serum albumin (HSA), influencing its biodistribution and ultimately its photodynamic therapy efficacy in vivo. Thus, the present work reports a biophysical characterization on the interaction between the anionic porphyrin TDFPPS and HSA by UV-visible absorption, circular dichroism, steady-state, time-resolved, and synchronous fluorescence techniques under physiological conditions, combined with molecular docking calculations and molecular dynamics simulations. The interaction HSA:TDFPPS is spontaneous (ΔG°