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3. （2017-09-20）JACS发表邓鹤翔团队药物指令化、程序化释放创新研究成果

（2017-09-20）JACS发表邓鹤翔团队药物指令化、程序化释放创新研究成果

   9月13日，化学与分子科学学院邓鹤翔教授团队在化学顶级期刊美国化学会志(Journal of the American Chemical Society，JACS)在线发表创新研究成果，首次提出单一药物的指令化释放、多组分药物的程序化释放新方法，此方法能够针对病人给药需求，精确设计药物的释放速度和达到峰值时间。研发出的“可编程”新型纳米药物载体为个性化、定制化医疗提供了新工具。

  药物释放的动力学基础为主客体相互作用，药物的释放曲线无法精确控制，这是因为克服主客体相互作用力所需活化能的能级通常是分立的，不可连续调控。在此项研究中，研究人员采用金属-有机框架材料（MOF）作为药物分子的新型载体，在结构中引入多种不同的有机官能团构建多元金属有机框架材料（MTV-MOF）。由于每一种官能团与药物分子的相互作用可以分别定量，因此MTV-MOF与药物分子的相互作用可以通过不同官能团的组合及组分的精确调控，在大范围内的连续调节药物的释放速率（调控幅度高达32倍）；以抗癌药物DOX为例，其达到释放峰值的时间也可以在17天和29天之间连续调节。此外，研究人员量化了主客体之间的相互作用，对于研究材料与客体分子之间的相互作用，尤其是弱相互作用（如静电、氢键、π-π，范德华力等）的定量提供了新的方法。通过这种对孔道化学环境在分子级别上的连续调控，研究人员首次实现了药物的指令化释放。值得关注的是这种方法不仅适用于单一药物分子的可控释放，而且可以用于多种药物组合的分别调控，即针对病患的实际需求，实现对药物释放曲线的精确“编程”。

  该论文题为《通过精确调控结合能实现程序化药物释放的多元金属有机框架材料》Multivariate Metal-Organic Frameworks for Dialing-in the Binding and Programming the Release of Drug Molecules (DOI: 10.1021/jacs.7b07392)。邓鹤翔教授为通讯作者，化学院博士生董志月为第一作者。其它作者包括化学院张先正教授、2013级本科生孙杨泽晟和2015级研究生褚君，他们在此研究工作中做出重要贡献。该项研究得到了基金委重大研究计划重点项目、培育项目、基金委面上项目、湖北省重点项目和武汉大学创新团队项目的支持。 
  

English version:

Writing Program for Drugs Release

A method was developed to program the release of single or multiple drug molecules

                                                                               by Hexiang Deng’s Group in Wuhan University, featured on JACS

It has been a dream for patients that only one magic pill is needed to cure their diseases. This might not be as unrealistic as it sounds due to the fast development in new drug release systems.

Generally, the dynamic of drug release is determined by the host-guest interactions between drug molecules and the carrier materials. The activation energy that quantifying the host-guest interaction was usually discrete, thus release profiles of the drug molecules were hardly controllable in a precise manner. A new article was published online on Sep. 15^th on JACS (Journal of the American Chemical Society) with the title ‘Multivariate Metal-Organic Frameworks for Dialing-in the Binding and Programming the Release of Drug molecules’ (DOI: 10.1021/jacs.7b07392). In this report, researchers from Wuhan University applied MOFs carrying multiple functional groups (MTV-MOFs) as new carriers to dial-in the right host-guest energy and achieved precise tuning of drug delivery.

The combination of functional groups can be varied and their ratios can be continuously tuned without altering the underlying topology of these porous materials, well-known for their tremendous surface area. Thus the drug release rate can be adjusted continuously over a wide range (regulatory amplitude up to 32 fold). Taking the release of anti-cancer drug DOX as example, the time of maximum release amount can be tuned between 17^th and 29^th day. In addition, the host-guest interaction was also correlated with an activation energy that quantified by the release profile of drug molecule, such quantification approach can also be applied to other weak interaction between materials and guest molecules such as static electricity, hydrogen bond, π-π interaction and Van der Waals force. It is noteworthy that this method not only works on single drug molecules, but also applicable for the delivery of multiple drugs, to tend to the actual need of patients in a programmable way. These MTV-MOFs also provide a new direction to achieve individualized and customized medical therapy.

The research team in College of Chmistry & Molecular Sciences of Wuhan University, China, was led by Prof. Hexiang Deng in collaboration with his colleague Prof. Xianzheng Zhang. Zhiyue Dong is its first author, the other authors, Yangzesheng Sun and Jun Chu also made significant contributions. This research was supported by the 1000 Talent Plan of China, National Natural Science Foundation of China (21471118, 91545205, 91622103), National Science Foundation of Jiangsu Province of China (ZXG201446, BK20140410), National Key Basic Research Program of China (2014CB239203), Key Program of Hubei Provence (2015CFA126) and Innovation Team of Wuhan University (2042017kf0232).