發(fā)布時(shí)間：2018-03-13 08:16

  本文選題：聚乙烯亞胺　切入點(diǎn)：基因載體　出處：《天津理工大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：在非病毒基因載體中,聚乙烯亞胺(PEI)陽(yáng)離子基因載體轉(zhuǎn)染效率極高,但卻有很高的細(xì)胞毒性,需要進(jìn)行優(yōu)化。在此,我們構(gòu)建了兩種基于PEI的基因載體。在體系一中,我們用環(huán)糊精(CD)交聯(lián)低分子量的PEI制得PEI-CD,用聚乙二醇修飾偶氮苯(Az)得到PEG-Az,以主客體作用構(gòu)建光刺激響應(yīng)性的PEI-CD/PEG-Az/DNA復(fù)合體。電勢(shì)測(cè)量發(fā)現(xiàn),聚乙二醇的引入能有效降低復(fù)合物納米粒子的電勢(shì),但在光刺激下并不能使PEG完全脫落,故選用谷胱甘肽響應(yīng)的二硫鍵連接Az與PEG,構(gòu)建PEI-CD/PEG-SS-Az/DNA復(fù)合體,它在光照與谷胱甘肽(GSH)的雙重作用下使PEG完全脫落,促進(jìn)DNA釋放。在體系二中,我們用苯硼酸修飾的PEI(PEI_(25000)-PBA)以及四羧基四苯基乙烯(TPE-(COOH)4)交聯(lián)聚合的PEI(PEI_(1800)-TPE)與DNA混合,制得PEI_(1800)-TPE/PEI_(25000)-PBA/DNA復(fù)合物納米粒子,該納米粒子中PBA的存在使其具有膜靶向性,可促進(jìn)基因載體進(jìn)入細(xì)胞。同時(shí),TPE衍生物的聚集誘導(dǎo)發(fā)光效應(yīng)能有效追蹤該基因載體在細(xì)胞內(nèi)的運(yùn)轉(zhuǎn)過(guò)程,使基因載體在細(xì)胞內(nèi)的運(yùn)轉(zhuǎn)機(jī)制變得可視化。
[Abstract]:In the non-viral gene vector, polyvinyleneimine (PEI) cationic gene vector is highly efficient, but it has high cytotoxicity and needs to be optimized. In this paper, we constructed two kinds of gene vectors based on PEI. PEI-CD was prepared by crosslinking low molecular weight PEI with cyclodextrin, and PEG-Az-modified by polyethylene glycol (PEG-Azazo). The photostimulation-responsive PEI-CD/PEG-Az/DNA complex was constructed by host-guest interaction. The introduction of polyethylene glycol can effectively reduce the electric potential of composite nanoparticles, but it can not completely shed PEG under photostimulation. Therefore, glutathione-responsive disulfide bond is used to connect Az and PEG to construct PEI-CD/PEG-SS-Az/DNA complex. In system 2, PEIPEI-1 modified with benzoboric acid was used to modify PEII-PEII-PBA) and tetracarboxylic tetraphenylethylene tetrachloroethylene (TPE-COOHH4) was crosslinked and polymerized, PEIPEII-PEII-PEI-1) was mixed with DNA. The PEI_(1800)-TPE/PEI_(25000)-PBA/DNA complex nanoparticles were prepared. The presence of PBA in the nanoparticles made them membrane targeting and promoted the entry of gene vectors into cells. At the same time, the aggregation induced luminescence effect of PEI_(1800)-TPE/PEI_(25000)-PBA/DNA derivatives can effectively track the translocation of the gene vectors in cells. To visualize the mechanism of gene vector translocation in cells.
【學(xué)位授予單位】：天津理工大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：Q78

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