新技术使用ATP作为针对目标抗癌药物递送的触发

生物医学工程研究人员已经开发出a new technique that uses adenosine-5’-triphosphate (ATP), the so-called “energy molecule,” to trigger the release of anti-cancer drugs directly into cancer cells. Early laboratory tests show it increases the effectiveness of drugs targeting breast cancer. The technique was developed by researchers at North Carolina State University and the University of North Carolina at Chapel Hill.

“This is a proof of concept, but we’ve demonstrated there is now a new tool for introducing anti-cancer drugs directly into cancer cells – and that should make drug treatments significantly more effective,” says Dr. Zhen Gu, senior author of a paper on the research and an assistant professor in the joint biomedical engineering program at NC State and UNC-Chapel Hill.

GU的研究小组开发了涂有汉壳的球形纳米颗粒，其包含透明质酸（HA），其与在某些癌细胞表面上发现的蛋白质相互作用。当靶癌细胞与HA接触时，细胞吸收整个纳米颗粒。

一旦进入癌细胞，纳米粒子的壳就会缩短，释放其有效载荷：嵌入具有致癌药物（DOX）的抗癌药物的复杂DNA分子的集合，其靶向癌细胞的细胞核。

DNA分子设计用于展开 - 并仅在与高ATP水平接触时才能释放DOX。高水平的ATP通常仅在电池内部发现，这意味着DOX被释放在核的醒目距离内 - 而不是无意中释放在细胞外。

“这是第一次ATP已被用作受控释放抗癌药物的分子触发，两者in vitroandin vivo，“纸博士博士博士表示，该文件的主要作者和联合生物医学工程计划的博士后研究员。ATP将化学能量在细胞内进行代谢。

在in vitro测试，对MDA-MB-231人乳腺癌细胞的新技术比不包含ATP靶向组分的技术更有效。

研究人员还在一个中测试了新技术in vivo模型，使用具有乳腺癌肿瘤的小鼠。研究人员发现，与其他技术相比，ATP靶向技术在抑制肿瘤生长方面明显更有效。

“我们还认为，我们将能够通过操纵特定领域的ATP水平来使技术更加针对性，”Gu说。

本文，“ATP触发抗癌药物交付”，3月11日发布自然通信。来自Gu的实验室的共同作者包括天岳江，博士。学生;rocco isanto，师父的学生;博士博士博士博士博士研究员。该研究得到了国立卫生研究院的支持，授予1UL1T001111111111111111，并从NC州提供资金。

- 船员 -

编辑注：这项研究摘要跟随。

“ATP-triggered anticancer drug delivery”

作者：Ran Mo，Tianyue Jiang，Rocco Disanto，Wanyi Tai，Zhen Gu，北卡罗来纳州立大学和北卡罗来纳大学在教堂山

发表：2014年3月11日，自然通信

迪伊：10.1038 / ncomms4364

抽象的：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 (IC50) of ATP-responsive nanovehicles is 0.24 [micrometer] on MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive ones. 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.