Interaction of Hematoporphyrin with Lipid Membranes

Natural or synthetic porphyrins are being used as photosensitizers
in photodiagnosis (PD) and photodynamic therapy (PDT) of malignancies
and some other diseases. Understanding the interactions between porphyrins
and cell membranes is therefore important to rationalize the uptake
of photosensitizers and their passive transport through cell membranes.
In this study, we consider the properties of hematoporphyrin (Hp),
a well-known photosensitizer for PD and PDT, in the presence of a
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
(POPC) bilayer that we use as a model system for protein-free cell
membranes. For this purpose, we employed 200 ns atomic-scale molecular
dynamics (MD) simulations for five systems containing the neutral
(Hp0) or the dianionic form (Hp2–) of
Hp and the POPC bilayer. MD simulations allowed one to estimate the
position, orientation, and dynamics of Hp molecules inside the membrane.
The dye molecules were found to reside in the phospholipid headgroup
area close to the carbonyl groups of the POPC acyl chains. Their orientations
were dependent on the protonation state of two propionic groups. Hp2– was found to have a lower affinity to enter the membrane
than the neutral form. The dianions, being in the aqueous phase, formed
stable dimers with a strictly determined geometry. Our results fully
supported the experimental data and provide a more detailed molecular-level
description of the interactions of photosensitizers with lipid membranes.