Construction Of Viscosity Flurescence Probe And Its Application In Pathological Model

Intracellular viscosity is considered to be an essential parameter in the cellular microenvironment with a significant role in maintaining normal cellular physiological activity.In general,abnormalities in intracellular viscosity are closely associated with various diseases so that real-time monitoring and study of intracellular viscosity have great significance.Small molecule fluorescent probes have the advantages of simplicity,sensitivity,specificity,minimal damage to cells and real-time response.The rapid development of fluorescence imaging technology has made it possible for small molecule fluorescent probes in biomedical applications.Accordingly,three small molecule fluorescent probes were constructed via the Twisted Intramolccular Charge Transfer(TICT)mechanism to monitor intracellular viscosity changes by fluorescent intensity and fluorescence lifetime,which investigate practical problems and discover the potential physiological significance of viscosity abnormalities in specific locations,providing a new avenue for early diagnosis and treatment of diseases.(1)Based on the TICT mechanism,a viscosity fluorescent probe,NBI-V,with simple synthesis,high response times,good stability,gorgeous biocompatibility and mitochondrial targeting ability was synthesized with benzindole salts as electron acceptor.The enhanced fluorescence intensity of drug-stimulated cells with increased viscosity was clearly observed by NBI-V.In addition,the probe NBI-V was used to visualize the viscosity in fatty liver and inflamed mice.It is expected to become an important diagnostic tool for metabolic diseases characterised by viscosity abnormalities.(2)Based on the TICT mechanism,a viscosity-sensitive fluorescent probe HT-V that actively targets hepatocytes is constructed by galactose residues as targeting groups for hepatocytes and connected to fluorophores via ether bonds.The probe has good optical properties with a maximum emission wavelength of616 nm and a higher response as high as 86 times,good biocompatibility and low cytotoxicity.Probe HT-V is able to specifically recognize hepatocytes,liver tissues and liver in mice.The difference in viscosity levels between normal and tumour cells has also been verified,providing the basis for specific targeting and imaging of the probe HT-V on liver cancer,enabling the diagnosis and in situ imaging of liver cancer in mice in vivo and providing a new method for the early diagnosis of liver cancer.(3)Based on the TICT mechanism,we constructed a novel amphiphilic molecular probe YF-V consisting of isofuranone and flavonoid with stable structure,good selectivity,fluorescence lifetime response and low cytotoxicity.The galactose residues were introduced to enhance the water solubility and biocompatibility.YF-V has been successfully applied to observe the dynamic viscosity changes induced by glucose at the cellular level via fluorescence lifetime,and also research the lesions in various tissues of diabetic mice at the tissue and organ level.It offers an excellent and visual approach for assessing organ damage and early diagnosis of diabetes...