Mo Ran, Jiang Tianyue, Sun Wujin, Gu Zhen
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA; Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA; Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Biomaterials. 2015 May;50:67-74. doi: 10.1016/j.biomaterials.2015.01.053. Epub 2015 Feb 14.
Stimuli-triggered drug delivery systems are primarily focused on the applications of the tumor microenvironmental or cellular physiological cues to enhance the release of drugs at the target site. In this study, we applied adenosine-5'-triphosphate (ATP), the primary "energy molecule", as a trigger for enhanced release of preloaded drugs responding to the intracellular ATP concentration that is significantly higher than the extracellular level. A new ATP-responsive anticancer drug delivery strategy utilizing DNA-graphene crosslinked hybrid nanoaggregates as carriers was developed for controlled release of doxorubicin (DOX), which consists of graphene oxide (GO), two single-stranded DNA (ssDNA, denoted as DNA1 and DNA2) and ATP aptamer. The single-stranded DNA1 and DNA2 together with the ATP aptamer serve as the linkers upon hybridization for controlled assembly of the DNA-GO nanoaggregates, which effectively inhibited the release of DOX from the GO nanosheets. In the presence of ATP, the responsive formation of the ATP/ATP aptamer complex causes the dissociation of the aggregates, which promoted the release of DOX in the environment with a high ATP concentration such as cytosol compared with that in the ATP-deficient extracellular fluid. This supports the development of a novel ATP-responsive platform for targeted on-demand delivery of anticancer drugs inside specific cells.
刺激触发型药物递送系统主要致力于利用肿瘤微环境或细胞生理信号，以增强药物在靶位点的释放。在本研究中，我们将主要的“能量分子”三磷酸腺苷（ATP）用作一种触发因素，以响应细胞内ATP浓度显著高于细胞外水平的情况，增强预加载药物的释放。我们开发了一种新的基于DNA-石墨烯交联杂化纳米聚集体作为载体的ATP响应型抗癌药物递送策略，用于阿霉素（DOX）的控释，该策略由氧化石墨烯（GO）、两条单链DNA（ssDNA，分别记为DNA1和DNA2）以及ATP适配体组成。单链DNA1和DNA2与ATP适配体一起在杂交时作为连接物，用于DNA-GO纳米聚集体的可控组装，这有效地抑制了DOX从GO纳米片层中的释放。在ATP存在的情况下，ATP/ATP适配体复合物的响应性形成导致聚集体解离，与ATP缺乏的细胞外液相比，这促进了DOX在诸如细胞质溶胶等高ATP浓度环境中的释放。这支持了一种新型ATP响应平台的开发，用于在特定细胞内靶向按需递送抗癌药物。
