Enhanced anticancer efficacy by ATP-mediated liposomal drug delivery.
A liposome-based co-delivery system composed of a fusogenic liposome encapsulating ATP-responsive elements with chemotherapeutics and a liposome containing ATP was developed for ATP-mediated drug release triggered by liposomal fusion. The fusogenic liposome had a protein-DNA complex core containing an ATP-responsive DNA scaffold with doxorubicin (DOX) and could release DOX through a conformational change from the duplex to the aptamer/ATP complex in the presence of ATP. A cell-penetrating peptide-modified fusogenic liposomal membrane was coated on the core, which had an acid-triggered fusogenic potential with the ATP-loaded liposomes or endosomes/lysosomes. Directly delivering extrinsic liposomal ATP promoted the drug release from the fusogenic liposome in the acidic intracellular compartments upon a pH-sensitive membrane fusion and anticancer efficacy was enhanced both in vitro and in vivo.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695 (USA); Molecular Pharmaceutics Division, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 (USA). rmo@ncsu.edu.
Ran
R
Mo
Tianyue
T
Jiang
Zhen
Z
Gu
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000378:metabolism*; D061986:MCF-7 Cells; D051379:Mice; D050997:Nanomedicine / Q000379:methods*
D008081:Liposomes; D000255:Adenosine Triphosphate
ATP; drug delivery; liposomes; nanomedicine; stimuli-responsive materials