Construction Of Targeting Vector Of 2-deoxy-D-glucose Gold Nanoparticle-loaded 20（S）-protopanaxadiol

Based on the excellent properties of gold nanoparticles,a gold nanotargeting carrier complex（2-DG-SH@Au NPs-PPD）loaded with 2-deoxy-D-glucose and 20（S）-protopanaxadiol was constructed.By constructing a gold nanoparticle targeting carrier for 2-deoxy-D-glucose and loading it with 20（S）-protopanaxadiol,on the one hand we investigated the targeted drug delivery and integrated the targeting function of 2-deoxyD-glucose with the drug delivery function of gold nanoparticles;on the other hand,we solved the problem of low solubility of 20（S）-protopanaxadiol,improved the bioavailability and combined with 2-deoxy-D-glucose to play a synergistic role.The paper consists of four main parts.The thesis consists of four main parts as follows.Firstly,synthesis and characterization of 2-deoxy-D-glucose thiol derivatives（2-DG-SH）.A triethylene glycol chain was attached to the C-2 position of 2-deoxy-Dglucose using a chemical synthesis method with the terminal substitution with a mercapto group.After protection,addition,substitution and deprotection steps,the thiol derivatives of 2-deoxy-D-glucose were obtained and the structures of the individual products in the reaction were identified by NMR spectroscopy.The reaction route was explored and screened to determine the best synthetic method.Secondly,synthesis,characterization and stability investigation of 2-DGSH@Au NPs targeting carriers.Au NPs of different sizes were synthesized using the sodium citrate reduction and seed growth methods,and self-assembled with 2-deoxyD-glucothiol derivatives to synthesize 2-DG-SH@Au NPs targeting carriers.The results of UV-Vis,transmission electron microscopy,infrared spectroscopy and dynamic light scattering showed that 2-DG-SH@Au NPs of different sizes were successfully synthesized with homogeneous size and good dispersion.The gold/sulfur ratios in 2-DG-SH@Au NPs were determined using inductively coupled plasma mass spectrometry.The absorbance changes of 2-DG-SH@Au NPs complexes under different conditions were determined using UV-Vis spectroscopy to investigate the stability of the complexes.Thirdly,2-DG-SH@Au NPs were used to transport the antitumour drug 20（S）-protopanaxadiol to synthesise 2-DG-SH@Au NPs-PPD targeted nanocarrier complexes.Characterization was performed by infrared spectroscopy and the drug loading rate encapsulation rate was determined using high performance liquid chromatography.The results showed that the 2-DG-SH@Au NPs-PPD drug-loading efficiency and The encapsulation efficiency was 32.6%,23.4%;23.3%,24.8%;28.6%,34.8%.All have good drug loading rate and encapsulation rates.Fourthly,the antitumor activity of 2-DG-SH@Au NPs-PPD was investigated.The cytotoxicity of the complexes was investigated by MTT assay against three types of cells,MCF-7,A549 and SGC.The results showed that 2-DG-SH@Au NPs-PPD exhibited better antitumor activity against all three cells,with stronger effects on MCF-7 and A549 than SGC.In this study,2-DG-SH@Au NPs were constructed with good carrier stability and dispersion.The modification of gold nanoparticles by 2-DG-SH can improve the efficiency of cellular uptake of nanoparticles,increase the in vivo circulation time of nanoparticles,solve the problems of rapid metabolism and short half-life of 2-deoxyD-glucose,and provide an option for the targeted delivery of subsequent chemotherapeutic drugs.The 2-DG-SH@Au NPs-PPD targeting nano-loaded drug complexes were obtained by using targeting carriers loaded with 20（S）-protopanaxadiol,which had good solubility and excellent anti-tumour activity.The combination of20（S）-protopanaxadiol and nanomaterials opened up new ideas for the application of chemotherapeutic drugs and added a new approach to tumour treatment.