本文選題：磁性　切入點(diǎn)：氧化鐵　出處：《吉林大學(xué)》2017年博士論文　論文類型：學(xué)位論文

【摘要】：本文以高溫?zé)岱纸夥椒ㄖ苽淞擞腿苄匝趸F納米顆粒,利用配體交換的方法將其轉(zhuǎn)移至水相中,并在納米顆粒表面引入可進(jìn)一步修飾的可反應(yīng)的馬來酰胺基團(tuán)。并針對(duì)腫瘤微環(huán)境中相關(guān)分子谷胱甘肽(GSH)設(shè)計(jì)構(gòu)建了具有二硫鍵結(jié)構(gòu)相連的靶向分子RGD和自身肽的多肽序列Arg-Gly-Asp的多肽分子,通過與納米顆粒表面馬來酰胺基團(tuán)反應(yīng),將多肽分子修飾到納米顆粒表面,成功制備了GSH響應(yīng)的納米分子影像探針。其配體中的二硫鍵結(jié)構(gòu)可被腫瘤微環(huán)境中的相關(guān)分子GSH還原形成巰基,并與相鄰納米顆粒上的馬來酰亞胺殘基反應(yīng),導(dǎo)致納米顆粒交聯(lián)聚集;我們系統(tǒng)的研究了探針在GSH作用下的誘導(dǎo)聚集行為,并通過對(duì)聚集體磁學(xué)性質(zhì)的研究,揭示了氧化鐵納米顆粒的聚集行為與磁共振信號(hào)對(duì)比度增強(qiáng)效果間的關(guān)系;通過小鼠巨噬細(xì)胞對(duì)探針的攝取來考察探針修飾自身肽后體外逃避免疫延長(zhǎng)血液循環(huán)時(shí)間的能力。隨后對(duì)探針進(jìn)行放射性核素標(biāo)記,制備得到了具有MRI/SPECT雙模態(tài)分子影像探針,并應(yīng)用于體內(nèi)腫瘤檢測(cè)。體內(nèi)與體外的MRI成像結(jié)果不僅證明了聚集可顯著增強(qiáng)分子探針的弛豫性能,而且實(shí)現(xiàn)了體內(nèi)腫瘤的雙模態(tài)成像。智能響應(yīng)型探針設(shè)計(jì)構(gòu)建的新穎之處在于表面修飾策略,不僅增強(qiáng)MRI造影效果,而且能夠逃避免疫吞噬,還可以主動(dòng)靶向及雙模態(tài)成像。而后,又設(shè)計(jì)制備Ca~(2+)誘導(dǎo)Fe_3O_4納米顆粒聚集制備了聚集體。在表面包被沙門氏菌抗體制備了免疫磁珠,并對(duì)沙門氏菌進(jìn)行分離捕獲實(shí)驗(yàn),獲得了較好的捕獲效率。
[Abstract]:In this paper, oil soluble iron oxide nanoparticles were prepared by high temperature thermal decomposition and transferred to water phase by ligand exchange. Furthermore, a reactionable Maleamide group was introduced on the surface of nanoparticles. The targeted molecule RGD and autopeptide with disulfide bond structure were designed and constructed for glutathione glutathione (GSH) related molecules in tumor microenvironment. Of the polypeptide sequence Arg-Gly-Asp, The polypeptide molecules were modified onto the surface of nanoparticles by reaction with the Maleamide group on the surface of nanoparticles. GSH responsive nanomolecular imaging probe was successfully prepared. The disulfide bond structure in the ligand can be reduced to sulfhydryl group by the related molecule GSH in the tumor microenvironment and react with the Maleimide residue on the adjacent nanoparticles. We systematically studied the induced aggregation behavior of the probes under the action of GSH, and studied the magnetic properties of the aggregates. The relationship between the aggregation behavior of ferric oxide nanoparticles and the contrast enhancement effect of magnetic resonance signal is revealed. The ability of the probe to evade immunity and prolong the blood circulation time was investigated by the uptake of the probe by mouse macrophages. Then the probe was labeled with radionuclide and the MRI/SPECT bimodal molecular imaging probe was prepared. The results of MRI imaging in vivo and in vitro not only proved that aggregation can significantly enhance the relaxation properties of molecular probes, The novel design of intelligent responsive probe is that the surface modification strategy can not only enhance the effect of MRI imaging, but also avoid immune phagocytosis. Then Ca~(2 was designed to induce the aggregation of Fe_3O_4 nanoparticles to produce aggregates. The immunomagnetic beads were prepared by coating the antibodies against Salmonella on the surface, and the isolation and capture experiments of Salmonella were carried out. Better capture efficiency is obtained.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R73-3;TB383.1

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