期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 130, 期 44, 页码 14739-14744出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja8050469
关键词
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资金
- U.S. National Science Foundation
- State of Louisiana, Louisiana State University
- U.S. National Institutes of Health [P41RR02250]
An exciting new direction in responsive liposome research is endogenous triggering of liposomal payload release by overexpressed enzyme activity in affected tissues and offers the unique possibility of active and site-specific release. Bringing to fruition the fully expected capabilities of this new class of triggered liposomal delivery system requires a collection of liposome systems that respond to different upregulated enzymes; however, a relatively small number currently exist. Here we show that stable, similar to 100 nm diameter liposomes can be made from previously unreported quinone-dioleoyl phosphatidylethanolamine (Q-DOPE) lipids, and complete payload release (quenched fluorescent dye) from Q-DOPE liposomes occurs upon their redox activation when the quinone headgroup possesses specific substituents. The key component of the triggerable, contents-releasing Q-DOPE liposomes is a trimethyl-locked quinone redox switch attached to the N-terminus of DOPE lipids that undergoes a cleavage event upon two-electron reduction. Payload release by aggregation and leakage of uncapped Q-DOPE liposomes is supported by results from liposomes wherein deliberate alteration of the trimethyl-locked switch completely deactivates the redox-clestructible phenomena (liposome opening). We expect that Q-DOPE liposomes and their variants will be important in treatment of diseases with associated tissues that overexpress quinone reductases, such as cancers and inflammatory diseases, because the quinone redox switch is a known substrate for this group of reductases.
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