本文選題：DNA納米結(jié)構(gòu)　切入點：膽固醇　出處：《中國科學院研究生院(上海應用物理研究所)》2017年碩士論文　論文類型：學位論文

【摘要】：DNA是生物體遺傳信息的載體,在生物的成長、發(fā)育、繁衍過程中發(fā)揮重要的作用。隨著納米技術的發(fā)展,DNA作為一種新興材料可用于合成各種納米結(jié)構(gòu)。由于基于DNA的納米結(jié)構(gòu)有高度可定制的幾何屬性、很好的可尋址性和生物相容性,且容易進行化學修飾,是一類很有潛力的生物醫(yī)學材料。但正常情況下,哺乳動物細胞對DNA材料的攝取效率較低,限制了其作為藥物載體的應用。因此,本文研究了不同配體連接的DNA納米結(jié)構(gòu)與細胞的相互作用,尤其是配體連接策略對細胞攝取效率的影響,以增強DNA納米結(jié)構(gòu)進入細胞的效率。主要研究成果如下:(1)膽固醇修飾的DNA鏈促進DNA四面體的細胞攝取我們利用修飾有膽固醇的DNA鏈能錨定到細胞膜上的性質(zhì),提高與其序列互補的DNA四面體的細胞攝取。我們觀察到,經(jīng)膽固醇DNA介導的DNA四面體能快速富集到細胞的質(zhì)膜表面,并快速被細胞攝取。在這一過程中,膽固醇DNA起到了類似于細胞表面受體的作用,因此我們將膽固醇DNA稱為“人工DNA受體”。該受體介導的細胞攝取還具有特異性,只能介導帶有互補序列手臂鏈的DNA四面體進入細胞。此外,我們還對DNA介導的攝取途徑進行探索,發(fā)現(xiàn)其是小窩蛋白依賴的攝取途徑。另外,我們發(fā)現(xiàn),利用膽固醇DNA介導DNA四面體攝取的方式無明顯細胞毒性,可用于提高DNA四面體運輸載體的細胞攝取。此外,膽固醇DNA能促進載帶阿霉素的DNA四面體進入細胞發(fā)揮藥效,產(chǎn)生更強的細胞毒性。(2)DNA-納米金核殼實現(xiàn)細胞內(nèi)雙模成像我們合成了具有空腔的DNA-納米金核殼結(jié)構(gòu),空腔內(nèi)可裝載拉曼分子。這種DNA-納米金核殼結(jié)構(gòu)可實現(xiàn)細胞內(nèi)雙模成像,即拉曼成像和暗場成像。細胞對不同表面修飾的核殼結(jié)構(gòu)的攝取效率不同,其中對同時修飾有DNA和RGD短肽的RGD/DNA-AuNPs攝取效率最高。
[Abstract]:DNA is the carrier of genetic information in organisms, in the growth and development of organisms, With the development of nanotechnology, DNA can be used as a new material to synthesize various nanostructures. Because nanostructures based on DNA have highly customizable geometric properties, Highly addressable, biocompatible and easily chemically modified, it is a promising biomedical material. However, under normal conditions, mammalian cells have low uptake efficiency of DNA materials. Therefore, the interaction between different ligand DNA nanostructures and cells was studied, especially the effect of ligand binding strategy on cell uptake efficiency. In order to enhance the efficiency of DNA nanostructures entering into cells. The main research results are as follows: 1) Cholesterol-modified DNA chains promote the uptake of DNA tetrahedron cells by using DNA chains modified with cholesterol to anchor to cell membranes. We observed that DNA tetrahedron mediated by cholesterol DNA can rapidly enrich to the surface of the plasma membrane of the cell and be rapidly ingested by the cell. Cholesterol DNA acts as a cell surface receptor, so we call cholesterol DNA an "artificial DNA receptor." the receptor also mediates cellular uptake. Only DNA tetrahedrons with complementary arm chains can be mediated into cells. In addition, we have explored the uptake pathway mediated by DNA and found that it is a fossa protein-dependent uptake pathway. Cholesterol DNA mediated DNA tetrahedron uptake was not cytotoxic and could be used to increase the cellular uptake of DNA tetrahedron transport vector. In addition, cholesterol DNA could promote the entry of DNA tetrahedron carrying adriamycin into cells. To produce more cytotoxic DNA-nanocrystalline gold core-shell cells, we have synthesized DNA-nano-gold core-shell structures with cavities, which can hold Raman molecules in the cavity. This DNA-nano-gold core-shell structure can be used for intracellular dual-mode imaging. That is Raman imaging and dark field imaging. Cell uptake efficiency of core-shell structure with different surface modification is different. Among them the uptake efficiency of RGD/DNA-AuNPs modified with DNA and RGD short peptides is the highest.
【學位授予單位】：中國科學院研究生院(上海應用物理研究所)
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：TB383.1;Q25

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