Study Of Sulfated Glyconanoparticles Induced Tumor Cells Apoptosis

The study found that polysaccharides in the human body,such as the glycosaminoglycan family,can affect the activity of proteins through polysaccharide-protein interactions,intervene in the transmission,transduction and regulation of signals,and deeply regulate multiple signal pathways in the life process.There are a large number of sulfate groups present on the sugar chains,and the patterns and densities of these sulfate groups jointly regulate the biological activity of the polysaccharides.However,the difference in pattern and density may have an effect on the activity of the protein.What role does these play in the life activities of the tumor cells,so as to exert its anti-tumor activity,remains to be further analyzed.In recent years,the field of nanotechnology has also been rapidly developed.Superparamagnetic nanoparticles are easy to prepare and have controllable dimensions.They have great potential in cell separation,targeted drug delivery,tumor hyperthermia,and magnetic resonance imaging.Based on the above researches,in this study,five kinds of N-acetyl glucosamines were prepared from N-acetyl glucosamine in HS double sugar units and modified to the surface of previously prepared Fe₃O₄@SiO₂ nanoparticles,followed by sulfation.Sulfated glyconanoparticles with different patterns were got.The gastric cancer cell MGC 80-3 was used as a model to study the effect of these five sulfated glyconanoparticle on the growth of tumor cells.Specifically include the following aspects:?1?Preparation of Core-shell Fe₃O₄@SiO₂ NanoparticlesFirstly,the solvothermal method was used to prepare water-soluble magnetic Fe₃O₄nanoparticles.Secondly,silicon was used to form core-shell Fe₃O₄@SiO₂ composite particles.The composition and morphology of the nanoparticles were characterized by X-ray diffraction?XRD?,X-ray photoelectron spectroscopy?XPS?and transmission electron microscopy?TEM?.The results show that the average particle size of Fe₃O₄ nanoparticles is estimated to be 90-120 nm by TEM analysis,and the average particle size of Fe₃O₄@SiO₂ nanoparticles is estimated to be 100-130 nm.The dynamic light scattering?DLS?test shows that the Fe₃O₄nanoparticles have a hydrate radius of 152 nm,while the Fe₃O₄@SiO₂ nanoparticles are 260nm.Afterwards,further analysis by XRD and XPS showed that the complete core/shell Fe₃O₄@SiO₂ nanoparticles were successfully prepared.Which showed that the Fe₃O₄ and Fe₃O₄@SiO₂ nanoparticles are well dispersed,uniform particle size and good appearance.?2?Preparation and Activity Evaluation of Sulfated Sugar NanoparticlesSubsequently,five different N-acetylglucosamines were synthesized and the selectively protected N-acetylglucosamine was modified on the surface of Fe₃O₄@SiO₂ nanoparticles by"click"chemical modification,followed by sulfation to give different sulfation patterns?3,4,6-S?3-S?6-S?3,6-S?4,6-S?glyconanoparticles.Through TGA analysis,the density of the five selectively protected N-acetylglucosamines were 1.35,0.45,0.46,0.50 and 0.50nmol/cm²,respectively.The sulfation degree of the five sulfated glyconanoparticles were 63%,69%,69%,64%and 66%,respectively,by the barium sulfate turbidity.MTT experiments showed that these sulfated sugar nanoparticles can induce cell death in MGC 80-3 cancer cells.In order to verify the reason for the appearance of the appeal phenomenon,the apoptotic behavior of the cells was measured by the FITC-Annexin V/PI double staining experiment.The results showed that in these five kinds of sugar nanoparticles,the difference in cell apoptosis related to the sulfated pattern of surface sugars.Among all of these glyconanoparticles,3,4,6-sulfated nanoparticles can induce the most significant apoptosis,and the early and late apoptotic rates were 41.7%and 34.2%at 200?g/mL.In order to further explore the mechanism of apoptosis,Western Blot analysis showed that it can regulate the intracellular Bcl-2/Bax pathway protein expression levels,and the cell apoptosis behavior in a concentration-dependent manner.