The inability of chemotherapeutic drugs to selectively kill cancer cells provides significant motivation for development of novel drug-delivery vesicles possessing cancer-specific targeting capabilities. Trigger-responsive, phospholipid-based vesicles (liposomes) have the potential to provide a time and space accurate pathway for delivery of liposome contents to targeted tumors. Quinone-functionalized phosphatidylethanolamine (Q–PE) liposomes are capable of releasing their encapsulated contents upon being triggered by a redox reaction, with the possibility of such a triggering event being achieved by upregulated hNQO1 in tumor tissues. Liposomal contents release is proposed to be the result of a phase transition of the PE lipid from its lamellar liquid-crystalline phase (Lα) to its hexagonal-II inverted micelle (H<sub>II</sub>) phase, which is induced by removal of the Q head group in the outer leaflet of Q–PE liposomes, followed by contact of apposed liposomes. Here, we report that the lytic contents release kinetics of Q–PE-based vesicles in vitro is regulated by lipid composition. This outcome is the result of lipid nature determining the van der Waals attractive forces, electrostatic interactions, and hydration repulsion among vesicles, thereby controlling the efficiency of lipsome aggregation and contact-mediated release. Furthermore, a small change in the hydrocarbon chain of the PE lipid has a large impact on the phase stability of a lipid system, and, therefore, its ability to maintain the lamellar phase crucial to liposome stability. In addition, the content mixing fusion of those contact-mediated vesicles was evaluated. The outcomes from the work here have the potential to yield control over the kinetics of triggered liposomal contents release, pointing to opportunities for design of Q-PE based systems capable of targeting diseases associated with quinone reductase overexpression, such as cancers and inflammatory diseases.

In vitro manipulation of stimuli-responsive liposomal contents release potentially activated by overexpressed hNQO1 in cancer cells

253rd National Meeting (2017)

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