Probing the interactions of phthalocyanine-based photosensitizers with model phospholipid bilayer by molecular dynamics simulations

Phthalocyanines (Pc) have received considerable attention in the design of photosensitizers for photodynamic therapy (PDT). It is of great interest to design novel Pc-based photosensitizer with improved biological efficiency, which largely relies on the understanding of the interactions of Pc with cell membranes at a molecular level. Here, via all-atom molecular dynamics simulations, we explored the interaction mechanism between a model phospholipid bilayer and three zinc Pc (ZnPc) molecules with different hydrophobicity in nature. We find that the adsorption and insertion behaviors of ZnPc molecules in the model bilayer are different due to the differing hydrophobicity and interaction patterns with phospholipids. Moreover, our simulations demonstrate that the conjunction of a ZnPc skeleton with a cholesterol moiety may reduce the intrinsic molecular rotation of ZnPc in membranes, presumably leading to an increase of the generation efficiency of reactive oxygen species for PDT. The molecular insights obtained here are likely to help improve the rational design of novel photosensitizers with enhanced cellular uptake and photocytotoxic activity.