1] Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27695, USA [2] Molecular Pharmaceutics Division, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA [3] State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27695, USA.
Nat Commun. 2014 Mar 11;5:3364. doi: 10.1038/ncomms4364.
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.
刺激触发药物递送系统已被越来越多地用于提高抗癌药物的生理特异性和按需治疗效果。在这里，我们利用三磷酸腺苷 (ATP) 作为触发抗癌药物可控释放的信号。我们证明，通过将 ATP 结合适体整合到 DNA 基序中进行功能化的聚合物纳米载体，当处于富含 ATP 的环境中时，可通过构象开关选择性地释放嵌入的阿霉素。在 MDA-MB-231 细胞中，ATP 响应纳米载体的半最大抑制浓度为 0.24 μM，与非 ATP 响应纳米载体相比，细胞毒性增加了 3.6 倍。具有透明质酸交联的外壳的 ATP 响应纳米载体，一种特异性的肿瘤靶向配体，提高了荷异种 MDA-MB-231 肿瘤小鼠的化疗抑制肿瘤生长的效果。这种 ATP 触发的药物释放系统提供了一种更复杂的药物递送系统，可以区分 ATP 水平以促进药物的选择性释放。
