[ Instrument network instrument research and development ] Cancer is a major disease threatening human life and health, and drug therapy (chemotherapy) is one of the effective methods to treat cancer. In order to further improve the efficacy and reduce toxic and side effects, the targeted delivery and precise release of anti-cancer drugs have become an important content of the research and development of anti-cancer drugs. However, how to accurately trace the delivery process, targeted drug release process, and biodistribution and metabolism of anticancer drugs in real-time and online is a difficult and core problem that urgently needs to be resolved by analytical science.
The team of Yanping Shi, a researcher from the Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, recently used multi-mode imaging analysis technology combining fluorescence imaging and mass spectrometry imaging to successfully achieve real-time accurate tracing of a new type of prodrug targeting delivery, release, distribution and metabolism of the colorectal. The whole process.
The researchers designed and synthesized a new type of azo prodrug AP-N=N-Cy, which consists of a prodrug molecule (AP) through a multifunctional azophenyl group and near-infrared fluorophore ( Cy) are connected together. The research results show that the azo-based prodrug can not only be used as a near-infrared probe that responds to azo reductase to track the drug delivery process in real time, but also can be used as a delivery platform for anticancer drug molecules (AdP). In the presence of azo reductase, the multifunctional azo phenyl group in AP-N=N-Cy will be broken to release AdP and Cy. Its azo phenyl group acts as a switch to turn on Cy fluorescence. The introduction gives the azo-based prodrug a unique fluorescent on-off characteristic. Based on the specific secretion of azo reductase in the colon, this azo prodrug achieves specific localized delivery and targeted release in the colon.
The azo-based prodrug can be taken orally, and has high stability and low toxicity before reaching the colon. In view of the synchronization between the release of anticancer drug molecules and the fluorescence opening process, fluorescence imaging methods can be used to accurately trace the delivery of anticancer drug molecules in vitro, in vitro and in vivo, and mass spectrometry imaging can be used to analyze AdP and Cy at the molecular level. Precise analysis of biological distribution in different tissues.
The research results were recently published in Analytical Chemistry, 2020, 92: 9039-9047. The first author of the article is Dr. Zhao Xiaobo from the team, the co-first author is associate researcher Ha Wei, and Shi Yanping is the corresponding author of the article. The above work was supported by the National Natural Science Foundation of China and the Youth Innovation Promotion Association of the Chinese Academy of Sciences.
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