ATP-triggered anticancer drug delivery

Ran Mo, Tianyue Jiang, Rocco DiSanto, Wanyi Tai and Zhen Gu ()
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Ran Mo: University of North Carolina at Chapel Hill and North Carolina State University
Tianyue Jiang: University of North Carolina at Chapel Hill and North Carolina State University
Rocco DiSanto: University of North Carolina at Chapel Hill and North Carolina State University
Wanyi Tai: University of North Carolina at Chapel Hill and North Carolina State University
Zhen Gu: University of North Carolina at Chapel Hill and North Carolina State University

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

Date: 2014
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DOI: 10.1038/ncomms4364

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