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

Autor: Costa-Tuna A; CQC-IMS, Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal., Chaves OA; CQC-IMS, Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal. Electronic address: otavioaugustochaves@gmail.com., Loureiro RJS; CQC-IMS, Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal., Pinto S; CQC-IMS, Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal., Pina J; CQC-IMS, Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal., Serpa C; CQC-IMS, Department of Chemistry, University of Coimbra, Rua Larga, 3004-535 Coimbra, Portugal. Electronic address: serpasoa@ci.uc.pt.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Jan; Vol. 255, pp. 128210. Date of Electronic Publication: 2023 Nov 20.
DOI: 10.1016/j.ijbiomac.2023.128210
Abstrakt: The 5,10,15,20-tetrakis(2,6-difluoro-3-sulfophenyl)porphyrin (TDFPPS 4 ) 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 4 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 4 is spontaneous (ΔG° < 0), strong, and enthalpically driven (ΔH° = -70.1 ± 3.3 kJ mol -1 ) into subdomain IIA (site I). Curiously, despite the porphyrin binding into an internal pocket, about 50 % of TDFPPS 4 structure is still accessible to the solvent, making aggregation in the bloodstream possible. In silico calculations were reinforced by spectroscopic data indicating porphyrin aggregation between bound and unbound porphyrins. This results in an adverse scenario for anionic porphyrins to achieve their therapeutical potential as photosensitizers and control of effective dosages. Finally, a trend of anionic porphyrins to have a combination of quenching mechanisms (static and dynamic) was noticed.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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