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

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.

Automated summary

In this study, the interaction between the photosensitizer hypericin and different cell membranes was investigated. The results showed that hypericin had a strong binding and penetration ability in DPPC and DOPC monolayers, while electrostatic repulsions played a major role in the interactions with DOPG and DOPS. The irradiation of DOPC monolayers containing hypericin resulted in material loss due to hydrocarbon chain cleavage, while the effects on irradiated DOPS and DOPG monolayers were mild and attributed to hypericin self-aggregation.