Research group of Professor Yuan Lin of Hunan University: from scratch design chemical stability near infrared molecular probe to evaluate high fidelity hepatotoxicity in vivo

Due to its excellent properties such as high tissue penetration and low background fluorescence interference, NIR fluorescence probes and imaging techniques are widely used in biomedical research However, due to the instability of conventional NIR clusters in practical applications, most NIR probes suffer from false signals Especially in some pathological environments, the conjugated structure of NIR fluorescent probe is destroyed and false signal is produced due to the excessive production of high reactive substances Therefore, it is very important to design a chemical stable NIR fluorescence probe to detect the target biological species accurately and avoid false signals Recently, the research group of Professor Yuan Lin of College of chemistry and chemical engineering of Hunan University has made new progress in this field Relevant research results were published in J am Chem SOC (DOI: 10.1021 / JACS 9b01374) Brief introduction to Professor Yuan Lin, professor and doctoral supervisor of National Key Laboratory of chemical biosensor and metrology, School of chemistry and chemical engineering, Hunan University He has obtained bachelor's degree and doctor's degree from South China University and Hunan University respectively, and engaged in postdoctoral research in the Department of chemistry, National University of Singapore Since 2012, he has successively served as assistant professor, associate professor and professor of Hunan University At present, more than 80 papers have been published in international academic journals, with a total citation of more than 6400 times, with an H index of 43 Since 2012, more than 40 papers have been published in journals such as J am Chem SOC (8 papers), angel Chem Int ed (6 papers), chem SCI (3 papers), anal Chem (3 papers), adv.funct mater, biomaterials, etc by correspondence or first author In 2016, he was supported by the National Science Foundation for outstanding young people, and in 2017, he was selected as a young talent of Hunan Province It is mainly engaged in the research of molecular probe and biological imaging, synthesis and application of organic light functional dyes Cutting edge scientific research achievements: the fluorescence imaging technology of in vivo high fidelity hepatotoxicity evaluation using chemically stable near-infrared molecular probes designed from scratch is an effective method to detect various biological analytes in cells and in vivo, which is simple, sensitive and noninvasive Among them, near infrared (NIR) fluorescent molecules are more popular because of their high tissue penetration depth and low spontaneous fluorescence, and they have obvious advantages in real-time tracking the changes of special analytes in biological systems, which is helpful for scholars' in-depth study of related diseases Although many NIR fluorescent probes with excellent properties have been reported to be used in various biological applications, due to the limitations of classical NIR dyes, it is still a challenging task to develop appropriate NIR probes for the accurate detection of biological analytes Recently, this research group and many other research groups have developed a series of new NIR fluorescent dyes with controllable fluorescence properties, which have been widely used in the design of NIR probes with good signal to back ratio However, most NIR probes still face the problem of false signal caused by poor chemical stability in practical application, so it is of great significance to develop chemically stable high-performance NIR fluorescent probes to achieve high fidelity detection of target analysis signal In addition, compared with the normal state, some highly active species in the disease state may be overexpressed, so the near-infrared probe itself is easy to be destroyed by these active substances before identifying the target analyte, resulting in false signals Dili is a typical pathological example The results showed that ONOO and lap could be used as early diagnostic indexes of DILI However, due to the high concentration of reactive oxygen species / reactive nitrogen and nucleophiles produced in liver injury, the structure of conventional NIR fluorescent probes will be destroyed, so most of the Dili fluorescent probes developed in the actual detection process still have false signal phenomenon Recently, Professor Yuan Lin's research team hopes to develop the NiO probe of ONOO − and lap to verify their design concept, and select Dili as a disease model to study the performance of the constructed NIR probe Figure 1 Schematic diagram of possible causes of false signal in near-infrared fluorescent probe (source: J am Chem SOC.) there are two main causes of false signal in near-infrared fluorescent probe (Figure 1): 1) poor selectivity: false positive signal caused by interference of other biomolecules in complex biological environment; 2) poor stability: The high active species in the biological system destroy the conjugated structure of dye and lead to false negative signal So far, most of the work has focused on improving the selectivity of probe itself to solve the problem of false positive signal However, due to the destruction of dye conjugation structure by highly active species, false negative signals are rarely concerned In this study, the author proposed a method combining dye screening and reasonable design (Fig 2) to develop a stable NIR dye with optically adjustable group On this basis, two kinds of high fidelity NIR fluorescent probes (NIR lap and NIR ONOO −) were constructed to detect the hepatotoxicity markers lap and ONOO − Both of these probes are highly sensitive and can accurately monitor the changes of lap and ONOO − in the course of Dili, so as to accurately evaluate the drug-induced hepatotoxicity and its treatment process In this study, a chemically stable near-infrared fluorescent dye platform with optically tunable groups was developed, which provides a convenient and effective tool for the development of probes used in related pathological environments Figure 2 Near infrared fluorescent dye screening (a) and the design diagram of new near infrared dye and probe (b) (source: J am Chem SOC.) using confocal fluorescence imaging, flow cytometry and other technologies, probe nir-lap was first applied to the visual detection of lap content in Dili cell model (figure 3) The imaging results showed that the activity of lap fluctuated with the increase of paracetamol content The probe was further used to evaluate the efficacy of liver protective drugs (NAC, GSH or Glu) in Dili cell model The results showed that the extent of these drugs to repair hepatocytes was dose-dependent, and the imaging results showed that when lap was used as a therapeutic index of hepatotoxicity, the effect of N-acetylcysteine (NAC), an FDA approved Dili therapeutic drug, was better than that of GSH and Glu Fig 3 Preliminary evaluation of the therapeutic effect of various liver protection drugs (source: J am Chem SOC.) nir-lap via caudal vein injection under the cell injury model induced by paracetamol The author conducted imaging analysis and pathological tissue section analysis of the liver site through the small animal in vivo imaging system (Fig 4) The results showed that nir-lap could monitor the changes of lap content in the process of acetaminophen induced liver injury and various drugs for protecting liver and protecting liver in real time, and preliminarily evaluate the therapeutic effect of various drugs for protecting liver and protecting liver in vivo Fig 4 Preliminary evaluation of the therapeutic effect of various liver protective drugs (source: J am Chem SOC.) under the model of acetaminophen induced liver injury in vivo In summary, based on the combination strategy of dye screening and rational design, the author developed chemically stable NIR fluorescence clusters with optically adjustable groups, and on this basis, constructed two kinds of high fidelity NIR fluorescence probes Nir-lap and NIR - ONOO − These fluorescent probes can not only detect lap and ONOO − in vitro with high sensitivity and selectivity, but also visualize the process of drug-induced liver injury in vivo with high fidelity Using these probes, the authors also preliminarily evaluated the therapeutic effect of six drugs for protecting liver and protecting liver on drug-induced liver injury In addition, the chemically stable NIR fluorophores with optically tunable groups developed in this study provide an effective fluorescent reporting unit for the development of "activated" NIR fluorescent probes applied in relevant pathological environments The research results were published in J am Chem SOC (DOI: 10.1021 / JACS 9b01374) under the title of "de novo design of chemical stability near infrared molecular probesfor high fidelity Footprint Evaluation in vivo" The corresponding author of this paper is Professor Yuan Lin from the school of chemistry and chemical engineering of Hunan University, and the first author is postdoctoral Cheng Dan of the research group, who is strongly supported by Professor Zhang Xiaobing from the school of chemistry and chemical engineering, as well as the excellent youth fund, general program and China Postdoctoral Science Fund of NSFC Review of previous reports: research group of Professor Yuan Lin of Hunan University: visual detection of renal oxidative damage by optical fluorescence probe 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.