Construction Of Lipid Droplet Visualization Fluorescent Probe Based On Naphthone Skeleton And Its Application Researc

Since lipid droplets play a key role in the regulation of lipid metabolism and energy metabolism,lipid droplet dysfunction and its related mechanisms are associated with a variety of pathological conditions.In addition,because cancer cells require excessive energy,accumulation of lipid droplets has been observed in a range of cancers.Despite recent recognition of the importance of lipid droplets and their relevance to metabolic diseases and cancer,many fundamental questions remain unanswered.Therefore,the construction of fluorescent probes to understand the determinants controlling lipid droplet formation and their interaction dynamics may contribute to our understanding of their role in the pathogenesis of metabolic diseases and cancer.In the first part,a novel AIE fluorescent probe with large Stokes shift for lipid droplet detection was constructed.With 6-methoxy-1-naphthalenone as fluorophore,boron fluoride and the adjacent thiazole ring were used to synthesize a large ring plane conjugate structure,and the probe DTO was synthesized.The experimental results show that the stokes displacement of the probe DTO is 125 nm,which can effectively avoid background interference and improve the detection sensitivity.Dynamic light scattering experiments also show that the luminescence mechanism of probe DTO belongs to AIE phenomenon.The results of viscosity experiment show that the probe DTO is very sensitive to the change of viscosity in the environment.Based on the excellent optical properties of the probe DTO,lipid droplets in Hep G2 cells were detected and co-localization experiments were carried out.The results showed that the probe DTO could specifically label the lipid droplets in cells and emit fluorescence signals.In addition,probe DTO also has the advantages of no-wash and rapid imaging capability,which has great advantages in the study of lipid droplet morphology and physiological function.The second part is the research and development of near infrared AIE fluorescent probe.AIE fluorescent probes CMDP-CF₃,CMDP-CN and CMDP-NO₂with different substituents were synthesized by condensation of 6-methoxy-1-naphthalenone and phenylacetonitrile.The optical properties of the three probes were tested,and only CMDP-NO₂was a near-infrared fluorescent probe with a maximum emission wavelength greater than 600 nm.To explore this experimental phenomenon,their molecular orbital energies were calculated.The calculated results are in good agreement with the experimental results.The dynamic light scattering experiment also shows that the luminescence mechanism of CMDP-NO₂belongs to AIE phenomenon.The viscosity test results showed that the CMDP-NO₂probe was very sensitive to the viscosity change in the environment.Based on the excellent optical properties of the probe CMDP-NO₂,lipid droplets in Hep G2 cells were detected and co-localization experiments were carried out.The results showed that the probe CMDP-NO₂could specifically label the lipid droplets in cells and emit fluorescence signals.Considering the advantages of the near-infrared fluorescent probe CMDP-NO₂in vivo imaging and its excellent ability to detect lipid droplets,we further studied the imaging application of the probe CMDP-NO₂in vivo zebrafish.The experimental results showed that the probe CMDP-NO₂could stain the lipid droplets in zebrafish,which is of great significance in studying the physiological processes of lipid production and consumption.In conclusion,AIE fluorescent probes have large stokes displacement,can effectively avoid background interference and improve detection sensitivity,and show good application potential in the visual detection of lipid droplets.Probe CMDP-NO₂success marks the fish lipid droplet is of great significance in the study of physiological processes such as lipid production and consumption,and also has a good application prospect in the visual diagnosis of some lipid droplet related metabolic diseases and cancers.