Efficient Delivering of a Photodynamic Therapy Drug into Cellular Membranes Rationalized by Molecular Dynamics

Photodynamic therapy (PDT) represents a most attractive therapeutic strategy to reduce side-effects of chemotherapy and improve the global quality of life of patients. Yet, many PDT drugs suffer from poor bioavailability and cellular intake, and thus, drug-delivering strategies are mandatory. In this article, we rationalize the behavior of a temoporfin-based PDT drug, commercialized under the name of Foscan, complexed by two β-cyclodextrin units, acting as drug carriers, in the presence of a lipid bilayer. Our all-atom simulations have unequivocally shown the internalization of the drug-delivering complex and suggest its possible spontaneous dissociation in the lipid bilayer core. The factors favoring penetration and dissociation have also been analyzed, together with membrane perturbation due to the interaction with the drug carrier complex. Our results confirm the suitability of this encapsulation strategy for PDT and rationalize the experimental results concerning its efficacy.