Design,Synthesis And Property Of Dual-Targeting Fluorescent Nanoprobes

Hydrogen sulfide（H₂S）and carbon monoxide（CO）are important gas signaling molecules in the human body,and they are involved in regulating many important physiological activities.However,when the concentration of H₂S and CO in the body are abnormal,it will cause many diseases,such as diabetes,inflammation,tumor disease,Alzheimer’s disease and so on.Fluorescent probes are widely used in biological detection and other fields due to their advantages of simple operation,fast response speed and good biocompatibility.In recent years,people have designed and developed a series of fluorescent probes for the detection of H₂S and CO in living bodies and cells.However,the majority of fluorescent probes are single targeted（cancer cell or subcellular organelle targeted）H₂S and CO fluorescent probes.In the biological environment of cancer cell subcellular organelle,they can not achieve their accurate detection function of H₂S or CO.Based on this,we designed and synthesized two fluorescent nanoprobes with dual-targeting（cancer cell and subcellular organelle targeting）to achieve precise detection of CO and H₂S in cancer cell of subcellular organelles.The main contents and results of this paper are as follows:1.Using 7-diethylamino-4-methylcoumarin as the skeleton,we designed and synthesized a sort of fluorescent probe of coumarin pyridine derivatives（DMC）that can detect CO.The fluorescent nanoprobe（HA-DMC）were prepared by co-precipitation combining DMC with modified hyaluronic acid（HA）.The results showed that the prepared fluorescent nanoprobes（HA-DMC）had the advantages of good water dispersibility,good long-term stability（>30days）and good biocompatibility.In addition,cellular experiments showed that HA-DMC selectively entered into HA receptor-positive cancer cells.HA-DMC was degraded by high levels of hyaluronidase in cancer cells and released positive charge DMC,which further accumulated in mitochondria.The probe realized the precise detection of CO in the mitochondria of cancer cells.2.Using triphenylamine derivatives as the basic framework,we designed and synthesized a dual-state fluorescent probe（TBSCN）that could detect H₂S.The fluorescent nanoprobe（HA-TBSCN）were prepared by co-precipitation of TBSCN and modified hyaluronic acid（HA）.In the presence of H₂S,2,4-dinitrobenzenesulfonate leaved,the intramolecular produced excited state proton transfer（ESIPT）effect,and then a strong hydrophobic and weakly liposoluble fluorescent dye was formed.The fluorescence intensity at 570 nm was gradually enhanced.The probe had the advantages of large Stokes shift（100nm）,excellent water dispersibility,photostability and high sensitivity.