表面性質(zhì)連續(xù)變化的金納米系列的制備及其誘導(dǎo)細(xì)胞自噬的初步研究
發(fā)布時(shí)間:2018-04-26 19:17
本文選題:金納米系列 + 功能化修飾; 參考:《山東大學(xué)》2015年碩士論文
【摘要】:自上世紀(jì)六十年代末諾貝爾獎(jiǎng)得主Richard Feynman首次提出納米科學(xué)技術(shù)這一概念,納米科技便飛速發(fā)展并滲透入能源、建筑、生物醫(yī)藥、環(huán)保、工業(yè)、生活等各個(gè)領(lǐng)域。隨著納米科技的廣泛應(yīng)用,納米材料正以各種不同的方式和途徑進(jìn)入我們所處的生態(tài)環(huán)境,并對(duì)生態(tài)環(huán)境和人類健康帶來(lái)潛在的危害。研究表明,納米顆粒的生產(chǎn)、運(yùn)輸及使用的整個(gè)過(guò)程都會(huì)造成其在環(huán)境中的釋放和擴(kuò)散。納米顆?梢越(jīng)呼吸暴露、皮膚暴露、口服暴露和注射暴露等途徑進(jìn)入人體,并經(jīng)淋巴循環(huán)、血液循環(huán)進(jìn)入機(jī)體各種臟器,引起機(jī)體應(yīng)激反應(yīng)。隨著對(duì)納米材料生態(tài)效應(yīng)研究的深入,我們亟需系統(tǒng)研究納米材料的性質(zhì)如何影響其生物效應(yīng),從而為科學(xué)、安全的使用納米材料提供理論支持。目前的研究表明,納米材料的成分、粒徑、形貌、表面性質(zhì)等可影響納米材料的生物效應(yīng)。其中納米—生物界面的主要作用力靜電相互作用,疏水相互作用,氫鍵相互作用,π-π共軛作用,空間位阻等在納米材料的生物效應(yīng)方面發(fā)揮關(guān)鍵性作用。為了系統(tǒng)闡明納米材料的表面性質(zhì)如何影響其生物效應(yīng),本課題組選擇了廣泛應(yīng)用于診斷、治療、載藥等領(lǐng)域的金納米材料作為模型,通過(guò)對(duì)其表面進(jìn)行功能化修飾,分別設(shè)計(jì)合成了表面親疏水性、電荷、氫鍵、Π鍵和空間位阻單一性質(zhì)連續(xù)變化的五種金納米系列用于生物效應(yīng)研究。本工作為納米材料表面Π鍵密度連續(xù)變化的金納米系列的設(shè)計(jì)、合成、表征及五種金納米系列對(duì)細(xì)胞自噬影響的初步研究。本工作第一部分采用酰胺縮合的方法將苯胺(含π鍵)和環(huán)己胺(不含π鍵)分別與硫辛酸反應(yīng),得到N-苯基硫辛酰胺和環(huán)己基硫辛酰胺兩種小分子配體,使用硼氫化鈉還原法將這兩種小分子配體按照一定的比例要求通過(guò)金硫鍵連接到金納米表面對(duì)其進(jìn)行功能化修飾,得到表面Π鍵密度連續(xù)變化的金納米系列,并利用TEM、DLS、Zeta電位等對(duì)金納米系列進(jìn)行表征。結(jié)果表明我們合成的六種金納米顆粒均為粒徑在5~7nm之間的疏水性球形納米粒子,其在溶液中基本都以較為穩(wěn)定的聚集態(tài)存在,符合我們的設(shè)計(jì)要求。本工作的第二部分研究了表面單一性質(zhì)連續(xù)變化的五種金納米系列對(duì)轉(zhuǎn)染了GFP-LC3的人星形膠質(zhì)瘤細(xì)胞系U87的自噬誘發(fā)能力,結(jié)果表明,親疏水性連續(xù)變化的金納米系列和表面電荷連續(xù)變化的金納米系列可以引起明顯的細(xì)胞自噬水平上調(diào),且隨著疏水性的增強(qiáng)以及表面電荷密度的增大細(xì)胞自噬水平提高,其他三種性質(zhì)連續(xù)變化的金納米系列誘發(fā)細(xì)胞自噬的能力較弱,且沒(méi)有表現(xiàn)出明顯的趨勢(shì)。本研究結(jié)果為合理、安全的利用金納米材料提供了理論基礎(chǔ)。
[Abstract]:Since Nobel laureate Richard Feynman first put forward the concept of nanotechnology in the late 1960s, nanotechnology has developed rapidly and penetrated into energy, architecture, biomedicine, environmental protection, industry, life and other fields. With the wide application of nanotechnology, nanomaterials are coming into our ecological environment in various ways and means, and bring potential harm to ecological environment and human health. It is shown that the whole process of production, transportation and use of nanoparticles will result in their release and diffusion in the environment. Nanoparticles can enter the human body through respiratory exposure, skin exposure, oral exposure and injection exposure, and through lymphatic circulation, blood circulation into various organs of the body, causing stress response. With the further study of the ecological effects of nanomaterials, we need to systematically study how the properties of nanomaterials affect their biological effects, so as to provide theoretical support for the scientific and safe use of nanomaterials. Recent studies have shown that the composition, particle size, morphology and surface properties of nanomaterials can affect the biological effects of nanomaterials. Among them, electrostatic interaction, hydrophobic interaction, hydrogen bond interaction, 蟺-蟺 conjugation and steric hindrance play a key role in the biological effects of nanomaterials. In order to elucidate how the surface properties of nanomaterials affect their biological effects, our team selected gold nanomaterials, which are widely used in the fields of diagnosis, treatment, drug loading and so on, as models, and modified their surfaces by functionalization. Five kinds of gold nanocrystals, including hydrophobic surface, charge, hydrogen bond, 蟺 bond and single steric resistance, have been designed and synthesized to study biological effects. This work is the design, synthesis, characterization and preliminary study of the effect of five kinds of gold nanocrystalline series on cell autophagy. In the first part of this work, aniline (containing 蟺 bond) and cyclohexylamine (without 蟺 bond) were reacted with lipoic acid by amide condensation method to obtain two small molecular ligands, N-phenylthioctylamine and cyclohexylthioctylamine, respectively. Using sodium borohydride reduction method, the two small molecular ligands were connected to the gold nanocrystalline surface by au S bond according to a certain proportion, and the au nanocrystalline series with continuous change in bond density were obtained. The gold nanocrystals were characterized by Tem DLSU Zeta potential. The results show that the six kinds of gold nanoparticles are hydrophobic spherical nanoparticles with the particle size between 5~7nm and they all exist in stable aggregates in solution, which meet our design requirements. In the second part of this work, we studied the autophagy inducing ability of five kinds of gold nanometers with continuous changes in the surface of human astroglioma cell line U87 transfected with GFP-LC3. The results showed that, The hydrophobicity of gold nanoseries and the surface charge of gold nanocrystalline series could increase the level of autophagy, and the level of autophagy increased with the increase of hydrophobicity and surface charge density. The ability of the other three series of gold nanoparticles to induce autophagy was weak and showed no obvious trend. The results provide a theoretical basis for the rational and safe use of gold nanomaterials.
【學(xué)位授予單位】:山東大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2015
【分類號(hào)】:TB383.1;O614.123
【共引文獻(xiàn)】
相關(guān)期刊論文 前1條
1 楊中東;何俊;;納米技術(shù)在現(xiàn)代家禽飼養(yǎng)業(yè)中的應(yīng)用[J];家禽科學(xué);2006年02期
,本文編號(hào):1807315
本文鏈接:http://sikaile.net/kejilunwen/cailiaohuaxuelunwen/1807315.html
最近更新
教材專著