The potential is great for liposome drug delivery systems that provide specific contents release at diseased tissue sites upon activation by upregulated enzymes; however, this potential will only come to fruition with mechanistic knowledge of the contents release process. NAD(P)H:quinone oxidoreductase type 1 (NQO1) is a target for reductively-responsive liposomes, as it is an enzyme upregulated in numerous cancer tissues and is capable of reducing quinone propionic acid (QPA) trigger groups to hydroquinones that self cleave from dioleolylphosphatidylethanolamine (DOPE) liposome surfaces, thereby initiating contents release. Here we report that the observed contents release is associated with a lamellar to inverted hexagonal phase transition (La?HII), based on 31P NMR lineshapes for QPA-DOPE giant unilamellar vesicles (GUVs) before and after chemical reductive activation. Furthermore, the rate of contents release is rapidly accelerated due to the presence of increasing amounts of palmitoyl-oleoyl phosphatidylethanolamine (POPE) in large unilamellar vesicles (LUVs).

Rapid contents release from QPA-DOPE containing vesicles as a result of a reduction-induced phase transition

245th National Meeting (2013)

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