Mechanisms of hypericin incorporation to explain the photooxidation outcomes in phospholipid biomembrane models

Author(s)

Pereira, Lucas S. A. ; Camacho, Sabrina A. ; Almeida, Alexandre M. ; Goncalves, Renato S. ; Caetano, Wilker ; DeWolf, Christine ; Aoki, Pedro H. B.

• Document type: Journal article
• Source: Chemistry and Physics of Lipids; v. 244, p. 11-pg., 2022-02-23.

Abstract

Cell membranes are the first barriers for drug binding and key for the action of photosensitizers (PS). Herein, we report on the incorporation of the PS hypericin into Langmuir monolayers of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) to represent eukaryotic cell membranes, and 1,2-dioleoyl-sn-glycero-3-phospho(1'-rac-glycerol) (DOPG) to mimic bacterial membranes. Surface pressure (pi) vs mean molecular area (angstrom) isotherms showed a high degree of interaction (binding, penetration and relative solubilization) of hypericin into DPPC and DOPC monolayers. On the other hand, electrostatic repulsions govern the interactions with DOPG and DOPS, favoring hypericin self-aggregation, as visualized by Brewster angle microscopy (BAM). Indeed, the larger domains in BAM were consistent with the greater expansion of DOPG monolayers with incorporated hypericin, owing to stronger electrostatic repulsions. In contrast to DPPC, light-irradiation of DOPC monolayers containing hypericin induced loss of material due to hydrocarbon chain cleavage triggered by contact-dependent reactions between triplet excited state of hypericin and chain unsaturations. The mild effects noted for both irradiated DOPS and DOPG monolayers are attributed to hypericin self-aggregation, which may have decreased the singlet oxygen quantum yield (Phi O-1(2)) via self-quenching, despite the increased instability induced in the monolayers. (AU)

• FAPESP's process: 18/16713-0 - Photodynamic therapy: from molecular effects in model systems toward photodynamic efficiency in cell culture
• Grantee: Pedro Henrique Benites Aoki
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/08077-6 - Photo-oxidation of Langmuir monolayers mediated by the hypericin photosensitizer
• Grantee: Lucas Sant Anna Pereira
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• FAPESP's process: 18/22214-6 - Towards a convergence of technologies: from sensing and biosensing to information visualization and machine learning for data analysis in clinical diagnosis
• Grantee: Osvaldo Novais de Oliveira Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/14692-5 - Photothermal therapy mediated by gold nanoparticles: from model systems of biomembranes toward in vitro culture of tumor cells
• Grantee: Sabrina Aléssio Camacho
• Support Opportunities: Scholarships in Brazil - Post-Doctoral