Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 53, Issue 23, Pages 5815-5820Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201400268
Keywords
ATP; drug delivery; liposomes; nanomedicine; stimuli-responsive materials
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Funding
- NC TraCS [550KR51307]
- NIH's Clinical and Translational Science Awards (CTSA) at UNC-CH [1UL1TR001111]
- NC State Faculty Research and Professional Development Award
- BME Department of UNC-CH
- NCSU
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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.
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