Research group of Guo Zhiqian and Zhu Weihong, East China University of science and technology: application of sequence response and logic gate in intelligent drug delivery system

The real-time monitoring of drug delivery and controlled release is one of the key links to achieve targeted and accurate treatment of tumor However, due to the complex physiological environment and heterogeneity of cancer, it is still a great challenge to rely on biomarker detection for in vivo programmed accurate diagnosis and treatment Recently, the research group of Professor Guo Zhiqian and Professor Zhu Weihong from the fine Institute of East China University of science and technology has made new progress in the field of near-infrared fluorescent prodrug In this work, a novel dual channel near infrared intelligent drug delivery system based on Boolean logic operation is proposed And logic gate with sequence response can effectively avoid nonspecific activation of prodrug In particular, the dual channel near-infrared fluorescence signal response realizes real-time tracking of drug release process, which can effectively reduce the side effects of anticancer drugs and real-time monitoring of drugs (chemical science, DOI: 10.1039 / c8sc02079e) In recent years, Professor Guo Zhiqian and Professor Zhu Weihong of East China University of science and technology focus on near-infrared fluorescent dyes A series of research work has been carried out, innovative development of high-performance near-infrared dyes based on pyranonitrile and design strategy for fine regulation of near-infrared pyranonitrile fluorescent dyes have been established, and relevant research results have been published in the Journal of the American Chemical Society JACS (j.am.chem.soc 2014, 136, 3579; j.am.chem.soc., 2016, 138, 5334); for the large conjugation system of near-infrared dyes The research group has developed a new type of near-infrared dye parent building block with independent intellectual property rights, which breaks through the limitation of traditional dye aggregation fluorescence quenching, establishes the structure-activity relationship between molecular structure design and performance regulation of quinolinonitrile dye, and significantly improves the dye fluorescence quantum efficiency, It successfully solved the problem of how to balance the wavelength expansion and efficiency improvement of near-infrared dyes (chem SCI., 2014, 5, 1383; angelw Chem Int ed., 2015, 54, 7275) On the basis of the previous work, the research group focused on expanding the application of near-infrared fluorescent groups in the field of precision medicine It is still very challenging to achieve accurate programmable diagnosis and treatment in complex biological environment, especially to eliminate the non-specific activation of "false positive" signal In this work, a novel and Boolean logic gate with sequence response was constructed by covalently linking two channel cyanine dye (CY) fluorescent prodrugs to the hydrophobic block of super sensitive pH responsive polymer The "dissociation release" process of sequential response of drugs in vivo was realized by using near-infrared dual channel fluorescence In this work, we use the design strategy of sequence response and logic gate to trace the process of prodrug in real time through two channels visualization, which effectively increases the targeting ability and precise release of drugs, and significantly improves the treatment efficiency of tumor The application of sequence response and logic gate in the process of "dissociation release" of intelligent drugs (source: Chemical Science) focuses on the super sensitive detection of pH difference between tumor cells (pH = 5.0-6.0) and plasma (pH = 7.4) by probe P (cy-s-cpt) P (cy-s-cpt) in a small pH range (PKA = 6.3, Δ pH on / off = 0.3), its near-infrared fluorescence signal at 830 nm showed significant enhancement When pH > pKa, i.e P (cy-s-cpt) is in the state of dense nano micelle, the dense and stable nano micelle state greatly reduces the penetration of GSH into the hydrophobic core containing cy-s-cpt, thus blocking the reaction between GSH and the disulfide bond in cy-s-cpt However, when pH < pKa, the micelle dissociation makes the excessive GSH can effectively induce the programmed release of CPT, and the dual channel near-infrared fluorescence response can realize the real-time monitoring of drug molecular release process Dual channel near-infrared fluorescence response for drug release monitoring (source: Chemical Science) In the sequence and logic response constructed in this study, output 1 corresponds to the near-infrared fluorescence signal of P (cy-s-cpt) at 830 nm, indicating whether the nanoparticles are activated and converted to the secondary form (i.e dissociation state); output 2 After the interaction between the dissociated prodrug system and GSH, with the change of fluorescence signal at 650 nm of the release of CPT, an ordered response and logic gate was successfully constructed to monitor the programmed release of drugs in real time Through cell test, the authors verified the two channel sequential and logical response behavior of P (cy-s-cpt) in cells P (cy-s-cpt) shows excellent tumor targeting ability based on dual channel near-infrared fluorescence imaging and dual channel high-resolution three-dimensional imaging at 830 and 650 nm The results of tumor inhibition experiment showed that compared with small molecule drugs, P (cy-s-cpt) could significantly reduce the side effects on normal tissues, and significantly improve the treatment efficiency through accurate identification and tumor specific programmed drug release Research on antitumor activity of P (cy-s-cpt) (source: Chemical Science) this work cleverly designed a sequence activated and logical dual channel near infrared nanoprodrug P (cy-s-cpt), which realized real-time monitoring of drug release, showed accurate tumor targeting and excellent and different biological distribution, and showed significant tumor treatment effect The and logic gate of sequence response provides a new idea for the development of precise programmable drug delivery system and intelligent biosensor probe This article was selected as "2018 chemical science household collection" and "2018 chemsci pick of the week collection" by chemical science, and was specially commented on by the section of "new & Events" of British National Chemical Society with the title of "targeting tumours" This work was mainly completed by Yan Chenxu, a doctoral student Professor Guo Zhiqian and Professor Zhu Weihong were co correspondents, and were carefully guided by academician Tian He The research results are jointly funded by the basic science center project of NSFC, the innovation research group project and the excellent youth fund project Review of previous reports of the research group of Professor Guo Zhiqian and Professor Zhu Weihong: research group of Professor Guo Zhiqian and Professor Zhu Weihong of East China University of science and technology Today, science and technology elements are increasingly valued in economic life, China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeangoapp, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.