Design And Synthesis Of Targeting Nanoprobes Based On Dendrimer PAMAM

Despite advances in prevention, risk assessment and treatment, the series ofcardiovascular and cerebrovascular diseases which are caused by atherosclerosis (As)remain the leading cause of morbidity and mortality in the world. Fifty percent of menand64%of women who suddenly die of coronary artery disease have no previoussymptoms according to the2008AHA statistics. The lion’s share is due to acutecoronary syndromes, which are predominantly triggered by plaque rupture or erosionand subsequent coronary thrombosis. So that through the identification the relatedsubstances of vulnerable plaques is the hot spot in the research field. In the early stageof vascular lesions occur and plaque rupture will appear inflammatory factor,myeloperoxidase (MPO) is over expression in the whole As plaque formation andrupture process, and effects on vascular inflammation. It is mainly through theoxidation. But at present, MRI molecular probe is the most potential in vivononinvasive imaging technology which has special targeted molecular. MRI is a kindof molecular and cellular levels of biological processes in the animal and human body,compared to other imaging categories, MRI can provide extremely high spatialresolution, high tissue contrast, and to carry out at the same time imaging anatomy.Dendrimers polyamidoamine (PAMAM) is a kind of high molecular, because ofits precise molecular structure, the height of the geometric symmetry, the surface of alarge number of functional groups and molecular chain growth with controllable, andhas good solubility, low toxicity, can be decomposed in vivo, and so on. So PAMAMis often used as medical carrier in the field of biomedical research.In the second chapter, First use of dispersion method, the third generationpolyamidoamine dendrimers were synthesized by Michael addition method and amidation method (G3.0), then through a series of chemical characterization provesthe successful synthesis of G3.0. Then we choose the dendrimer (G3.0) as the carrierand based on iron oxide nanoparticles (IONPs) for MRI imaging agent. The G3.0switch to IONPs surface, abbreviated it as G3.0@IONPs. Further, by doublecarboxylated polyethylene glycol (PEG-(COOH)2) bonded to the targeting of MPOtargeting molecules5-serotonin, the other end grafted onto the surface of G3.0, thusobtained5-HT-PEG-G3.0@IONPs. All of the structures were characterized by FT-IRwhich could confirm that the products were successfully prepared. The sizes ofparticles were tested by dynamic light scattering(DLS) and also observed undertransmission electron microscope(TEM).According to the tests, the nanoparticlesshowed a spherical and monodispersed structures, and DLS result showed that thediameters of5-HT-PEG-G3.0@IONPs were about31nm, TEM result was about10nm, respectively. The standard curve of5-HT was portrayed based on thecharacteristic absorption peak at276nm in the UV-Vis test. Then the amount of5-HTgrafted on the final products was defined and the content of5-HT was6.19μg/mg.The results of thermogravimetric analysis (TGA) showed that about2wt%iron oxidewas in the nanoparticles, and vibrating sample magnetometer (VSM) revealed thesuperparamagnetism of5-HT-PEG-G3.0@IONPs nanoparticles, then the saturationmagnetization was1.47A m2/kg. Then for5-HT-PEG-G3.0@IONPs in targetingatherogenesis and plaque excessive expression of early MPO to provide a goodscientific basis.In the third chapter, the main research is the use of modified Gd on thedendrimer PAMAM system. the medicine to be generally used in the Gd3+contrastagent. It can improve the imaging contrast agents of low molecular in vivo whichdisadvantages of short cycle, higher toxicity. First of all, through the doublecarboxylic polyethylene glycol (PEG-(COOH)2) bonded to targeting molecule5-HT,then connected to G3.0, abbreviated it as G3.0-PEG-5-HT. And then Gd throughDTPA chelated on the surface of the G3.0-PEG-5-HT, abbreviated it as 5-HT-PEG-G3.0-DTPA-Gd. All of the structures were characterized by1H NMR andFT-IR which could confirm that the products were successfully prepared. The sizes ofparticles were tested by dynamic light scattering (DLS). According to the tests, thenanoparticles showed a spherical and monodispersed structures, and result showedthat the diameters of5-HT-PEG-G3.0-DTPA-Gd were about10.3nm. The standardcurve of5-HT was portrayed based on the characteristic absorption peak at276nm inthe UV-Vis test. Then the amount of5-HT grafted on the final products was definedand the content of5-HT was11.52μg/mg. The results of thermogravimetric analysis(TGA) showed that about15.6wt%Gd oxide in the nanoparticles.In a word, we successfully synthesized two kinds of nanoparticles with potentialtarget value, and verify the successful synthesis of them through a variety of chemicalcharacterization. So provide the basis for the As early medical diagnosis andidentification of unstable plaque.