發(fā)布時(shí)間：2018-01-11 23:34

  本文關(guān)鍵詞：兼具磁熱功能的幾種多響應(yīng)性納米載藥體系的構(gòu)建及其在腫瘤成像中的應(yīng)用　出處：《內(nèi)蒙古大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 溫度響應(yīng) pH響應(yīng) 磁熱 PDT 藥物緩釋 細(xì)胞成像

【摘要】：隨著人類科學(xué)技術(shù)與醫(yī)學(xué)的發(fā)展,很多科研工作者將越來越多的研究興趣集中在人類尚不能完全掌握治愈方法的癌癥的診斷和治療上,繼而用于治療癌癥的藥物相繼被研發(fā)出來,但是臨床發(fā)現(xiàn)目前的一些藥物存在一些問題尚待解決,如其容易被正常細(xì)胞非特異性內(nèi)吞,損壞正常細(xì)胞的增殖等,因此,本論文主要設(shè)計(jì)和構(gòu)建了針對(duì)腫瘤細(xì)胞的具有多響應(yīng)性的藥物控釋體系,以避免在未來的治療過程中對(duì)正常細(xì)胞的損害。本論文主要設(shè)計(jì)了以下四個(gè)刺激響應(yīng)型藥物控釋體系:1.設(shè)計(jì)了一種溫度和pH雙響應(yīng)的藥物緩釋體系Fe3O4/PNIPAM/5-Fu@mSiO2-ZnO。將Fe3O4粒子的磁熱功能和溫敏型聚N-異丙基丙烯酰胺(PNIPAM)的最低臨界溫度(LCST)結(jié)合起來實(shí)現(xiàn)對(duì)藥物的溫度響應(yīng)性控釋。在接近腫瘤細(xì)胞時(shí),ZnO量子點(diǎn)的pH響應(yīng)性可以保證藥物在腫瘤細(xì)胞中釋放,從而避免藥物泄露引起的副作用。實(shí)驗(yàn)結(jié)果表明該體系在不同的pH(5.0和7.4)和溫度(25℃和45℃)下均具有明顯的響應(yīng)性。此外,MTT實(shí)驗(yàn)結(jié)果表明非載藥體系的細(xì)胞存活率最低為78%,而相同濃度的載藥體系的細(xì)胞存活率僅為20%。2.設(shè)計(jì)了一種具有溫度響應(yīng)性和細(xì)胞成像功能的藥物緩釋體系Fe3O4/PNIPAM/5-Fu@mSiO2-CHI/R6G。實(shí)驗(yàn)結(jié)果表明濃度為 10mg/ml 的Fe3O4/PNIPAM/5-Fu@mSi02-CHI/R6G 在 37.680e 的磁場(chǎng)強(qiáng)度下只需要 300 秒就可以達(dá)到45℃(腫瘤治療溫度)。此外,該體系在不同溫度下(25℃和45℃)的藥物釋放實(shí)驗(yàn)表現(xiàn)出了優(yōu)異的溫度響應(yīng)性。其細(xì)胞毒性實(shí)驗(yàn)和成像實(shí)驗(yàn)證明該藥物載體具有很好的生物相容性和細(xì)胞成像功能。3.構(gòu)建了 一種兼具熱療、藥療和光動(dòng)力學(xué)療法三功能的藥物緩釋體系Mn02/Fe3O4/5-Fu@CHI/R6G。該體系中Mn02可通過與體內(nèi)谷胱甘肽(GSH)的反應(yīng)實(shí)現(xiàn)對(duì)藥物的GSH響應(yīng)性釋放,極大的降低了對(duì)正常細(xì)胞的損傷。測(cè)試結(jié)果表明該體系在40mMGSH下(該濃度為腫瘤細(xì)胞特征濃度)的釋放量要明顯高于10mM(正常細(xì)胞)下的。此外,在可見光照射下該體系可以在酸性條件下與H202作用產(chǎn)生單線態(tài)的氧,可以抑制腫瘤細(xì)胞的生長(zhǎng),從而實(shí)現(xiàn)對(duì)腫瘤細(xì)胞的光動(dòng)力學(xué)協(xié)同治療。我們還對(duì)該體系進(jìn)行了細(xì)胞毒性和細(xì)胞成像方面的研究。4.基于片層石墨烯優(yōu)異的生物相容性和導(dǎo)電性能,設(shè)計(jì)了一種石墨烯(GO)基的藥物緩釋體系Fe3O4/5-Fu/PNIPAM@mSiO-GO。在可見光的照射下,該藥物載體在酸性條件中催化H202產(chǎn)生單線態(tài)氧,目的在于殺死乏氧腫瘤細(xì)胞。實(shí)驗(yàn)結(jié)果表明該藥物緩釋體系在不同溫度下(25℃和45℃)下表現(xiàn)出了很好的溫度響應(yīng)性。其溫度控釋性能一定程度上降低了對(duì)正常細(xì)胞的副作用。MTT實(shí)驗(yàn)證明該體系具有一定的生物相容性和殺死腫瘤的效果。
[Abstract]:With the development of science and technology and medicine, more and more researchers focus on the diagnosis and treatment of cancer which cannot be cured completely. Then the drugs used to treat cancer have been developed one after another, but there are still some problems to be solved in clinic, such as its easy to be ingested by normal cells, damage the proliferation of normal cells and so on. Therefore, this paper mainly designed and constructed a multi-response drug delivery system for tumor cells. In order to avoid damage to normal cells in the course of future treatment, the following four stimulus-responsive drug controlled release systems were designed:. 1. A kind of drug sustained release system Fe3O4 / PNIPAM / 5-FumSiO2-ZnO was designed. The magnetocaloric function of Fe3O4 particles and thermo-sensitive poly-N-. Isopropyl acrylamide. The lowest critical temperature (LCP) of PNIPAM is combined to achieve the thermo-responsive controlled release of the drug, when it is close to the tumor cells. The pH response of ZnO quantum dots can guarantee the release of drugs in tumor cells. In order to avoid side effects caused by drug leakage, the experimental results show that the system has obvious responsiveness at different pH(5.0 and 7.4) and temperature of 25 鈩，

本文編號(hào)：1411762