Stabilization and quinone reduction-triggered release property of DOPE liposomes

Liposomes composed of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) cannot readily form stable liposomes on their own because of their packing parameter characteristics. Therefore, a helper molecule is required to maintain a lamellar bilayer. In this study, a quinone reduction-responsive molecule (QRM) by conjugating a trimethyl lock quinone moiety with mPEG-NH2, and it was applied to the stabilization of DOPE liposomes. The structure of the synthesized QRM was confirmed by 1H NMR, and its reduction responsiveness was evaluated using sodium dithionite (Na2S2O4). After Na2S2O4 treatment, reductive cleavage of QRM was confirmed by 1H NMR and UV–spectroscopy. Surface tension measurements showed that QRM exhibited amphiphilic behavior, and DOPE liposomes containing QRM were most effectively formed at a DOPE/QRM mass ratio of 25:1. TEM analysis confirmed that the liposomes were successfully formed with a lamellar structure. Under reductive conditions, Lip-QRM(25:1) showed a marked increase in particle size and concentration-dependent release after Na2S2O4 treatment. These results demonstrate that QRM stabilizes DOPE liposomes under normal conditions, but under reductive conditions it undergoes structural cleavage, thereby destabilizing the membrane and inducing release. Therefore, QRM has potential to be used as a quinone reduction-triggered helper molecule for reductively responsive DOPE liposomes.