本文選題：磁性熒光納米探針 + 聚多巴胺��； 參考：《南京大學(xué)》2015年博士論文

【摘要】：納米材料由于其尺寸小,比表面積大,易修飾,物理化學(xué)性質(zhì)獨(dú)特,生物相容性良好等優(yōu)點(diǎn),廣泛應(yīng)用于生物,醫(yī)藥,能源,催化和環(huán)境等領(lǐng)域。特別是通過與具有特異性識(shí)別能力的生物分子聯(lián)用,構(gòu)建多功能的納米探針和藥物載體,已應(yīng)用于癌細(xì)胞的熒光標(biāo)記、磁性分離、基因轉(zhuǎn)染、熱療和藥物治療等眾多領(lǐng)域。本論文致力于利用納米材料的光、磁、熱學(xué)性質(zhì)來調(diào)控生物分子的催化、識(shí)別功能,以腫瘤細(xì)胞中異常表達(dá)的生物分子為靶標(biāo),構(gòu)建多功能的生物納米探針用于癌細(xì)胞特異性標(biāo)記、靶向藥物傳輸和可控釋放。主要內(nèi)容如下：1、多層核殼結(jié)構(gòu)的磁性熒光納米探針用于靶細(xì)胞成像與芯片內(nèi)分離聚多巴胺不僅能夠輕易地包附在各種界面和無機(jī)納米粒子表面,而且在堿性溶液中能與具有親核基團(tuán)的生物分子高效偶聯(lián),是制備生物納米探針的理想修飾界面。我們合成了一種多層核殼結(jié)構(gòu)磁性熒光粒子Fe3O4/SiO2/CdSeTe@ZnS-SiO2/聚多巴胺,并通過聚多巴胺與氨基、巰基或羧基修飾的DNA適配體偶聯(lián),用于對(duì)靶向癌細(xì)胞表面受體的特異性識(shí)別和定量評(píng)估。同時(shí),利用磁性熒光探針在微流控芯片中對(duì)兩種白血病細(xì)胞HL-60和K562的混合樣品進(jìn)行了在線識(shí)別、熒光標(biāo)記和磁性分離。與傳統(tǒng)細(xì)胞分離方法相比,本方法具有步驟簡便、操作時(shí)間短、分離效率和回收率高等特點(diǎn),在生物樣品的成像與分離領(lǐng)域有潛在的應(yīng)用價(jià)值。2、DNA hybrid為納米門的多功能介孔硅納米載體用于藥物靶向運(yùn)輸與可控釋放理想的納米藥物載體具備以下特性：特異性地識(shí)別癌癥細(xì)胞；到達(dá)靶細(xì)胞前藥物零釋放；被靶細(xì)胞內(nèi)的引發(fā)劑觸發(fā)并可控地釋放藥物。我們選取細(xì)胞內(nèi)異常表達(dá)的microRNA為觸發(fā)劑,設(shè)計(jì)了一種熒光示蹤的、適配體靶向的納米藥物載體,考察了藥物載體在靶細(xì)胞內(nèi)的吸收、藥物釋放和治療效果。該載體以可編碼的DNA hybrid為納米門,通過部分堿基互補(bǔ)配對(duì)將藥物分子封裝在納米載體內(nèi)部。結(jié)果表明,在適配體介導(dǎo)的內(nèi)吞作用下,藥物載體能夠選擇性地在HeLa細(xì)胞內(nèi)富集,并被癌細(xì)胞內(nèi)過表達(dá)的miR-21觸發(fā)藥物釋放。同時(shí),調(diào)節(jié)細(xì)胞內(nèi)microRNA的表達(dá)水平能夠調(diào)控藥物的釋放速度,這種藥物和基因協(xié)同治療的方法為人類疾病的個(gè)性化治療提供了新的策略。3、基于MNAzyme原位擴(kuò)增技術(shù)的多功能納米器件用于細(xì)胞內(nèi)microRNA的多通道成像,邏輯運(yùn)算和可控藥物釋放microRNA在癌癥的發(fā)生,發(fā)展,轉(zhuǎn)移過程中起著重要的作用,是極具潛力的癌癥診斷生物標(biāo)志物和治療靶點(diǎn)。但是microRNA在細(xì)胞內(nèi)的表達(dá)水平比較低。我們利用具有光熱性質(zhì)的納米金棒和具有催化活性的MNAzyme發(fā)展了一種可編碼的多功能納米器件,用于microRNA的特異性識(shí)別和原位擴(kuò)增,考察了細(xì)胞內(nèi)microRNA的多通道檢測和可控藥物釋放。利用MNAzyme的可編碼、特異性識(shí)別和催化切割能力,不僅能夠構(gòu)建turn-on的熒光探針,實(shí)現(xiàn)細(xì)胞內(nèi)痕量microRNA的多通道檢測和熒光成像,而且能夠循環(huán)放大microRNA觸發(fā)和控制藥物釋放的能力,增強(qiáng)藥物載體的治療效果,為疾病的診斷,預(yù)后監(jiān)測,藥物和基因聯(lián)合治療提供通用的一體化設(shè)計(jì)思路。4、多重溫度響應(yīng)的智能納米載體用于活體內(nèi)熱控吸收與microRNA/ATP介導(dǎo)的可控釋放在癌癥的治療過程中,提高藥物載體的靶向性和可控性能夠提高治療效果,減輕副作用。我們構(gòu)建了一種多重溫度響應(yīng)的、表面性質(zhì)可調(diào)的智能納米載體,用于siRNA和Dox的靶向運(yùn)輸與同步可控釋放。納米載體表面的PEG殼層有效延長了載體在血液中的循環(huán)時(shí)間,減輕了血液中酶類對(duì)siRNA的降解,增加了載體在腫瘤部位的被動(dòng)富集。通過近紅外激光控制,實(shí)現(xiàn)了納米載體在細(xì)胞和活體腫瘤組織的特異性識(shí)別與吸收。同時(shí)選擇細(xì)胞內(nèi)過表達(dá)的microRNA為引發(fā)劑,ATP為燃料分子,通過觸發(fā)Toehold介導(dǎo)的級(jí)聯(lián)擴(kuò)增反應(yīng)實(shí)現(xiàn)了siRNA/Dox的同步釋放,提高了治療效果,有效抑制了腫瘤的生長,達(dá)到了協(xié)同治療的作用。
[Abstract]:Because of its small size, large surface area, easy modification, unique physical and chemical properties and good biocompatibility, nanomaterials are widely used in biological, medical, energy, catalysis and environmental fields. In particular, multi-functional nanoprobes and drug carriers have been used in combination with biological molecules with specific recognition ability, and have been applied to the application of nano probes and drug carriers. The fluorescent labeling of cancer cells, magnetic separation, gene transfection, thermotherapy and drug therapy. This paper is devoted to the use of the optical, magnetic and thermal properties of nanomaterials to regulate the catalysis of biomolecules and identify the functions of biomolecules expressed in tumor cells, and to construct a multifunctional biological nano probe for cancer cells. Specific markers, targeted drug delivery and controlled release. The main contents are as follows: 1, the magnetic fluorescent nanoprobes of multi-layer nuclear shell structures are used in target cell imaging and in chip separation polydopamine not only can easily be attached to the surface of various interfaces and inorganic nanoparticles, but also in alkaline solutions with nucleophilic groups. We have synthesized a multi-layer nuclear shell structure magnetic fluorescent particle Fe3O4/SiO2/CdSeTe@ZnS-SiO2/ polydopamine, coupled with the DNA aptamers modified by polyamine and amino, sulfhydryl or carboxyl groups to identify and quantify the specific surface receptor on the target cancer cells. At the same time, the magnetic fluorescence probe was used in the microfluidic chip to identify the mixed samples of the two leukemia cells HL-60 and K562 on line, the fluorescence labeling and the magnetic separation. Compared with the traditional cell separation method, this method has the advantages of simple steps, short operation time, high separation efficiency and high recovery rate, and the imaging of biological samples. With potential application value.2, DNA hybrid is a multifunctional mesoporous silicon nanoscale carrier for drug targeting transport and controlled release of nanoscale drug carriers with the following characteristics: specific identification of cancer cells; zero release of drugs before reaching the target cells; triggers in target cells and controllable. We selected the abnormal expression of microRNA as a trigger, designed a fluorescent tracer, an aptamer targeted nano drug carrier, investigated the absorption, drug release and therapeutic effect of the drug carrier in the target cells. The vector used the encoded DNA hybrid as the nano gate and the complementary pairing of some bases. The molecules are encapsulated inside the nanoscale. The results show that the drug carrier can be selectively enriched in HeLa cells and release the drugs over expressed miR-21 in the cancer cells under the aptamer mediated endocytosis. At the same time, the regulation of the expression level of microRNA in the cell can regulate the release rate of the drug, and this drug and gene are synergistic. The method of treatment provides a new strategy.3 for individualized treatment of human diseases. Multi-functional nanodevices based on MNAzyme in situ amplification technology are used for multichannel imaging of microRNA in cells. Logical operations and controlled drug release microRNA play an important role in cancer occurrence, development, and metastasis, which are potential cancers. Diagnosis of biomarkers and therapeutic targets. However, the expression level of microRNA in cells is low. We have developed a coded multifunction nano device using nano gold rods with photothermal properties and catalytic activity of MNAzyme to identify and amplify microRNA, and investigate the multiple channels of intracellular microRNA. Detection and controlled drug release. The coding, specific identification and catalytic cutting ability of MNAzyme can not only construct turn-on fluorescent probes, realize multichannel detection and fluorescence imaging of trace microRNA in cells, but also circulate and amplify the ability of microRNA to trigger and control the release of drugs, and enhance the therapeutic effect of drug carriers. For the diagnosis of the disease, the monitoring of the prognosis, the combination of drugs and gene therapy provides a general idea of integrated design.4. The multi temperature response intelligent nanoscale is used in the treatment of cancer by internal heat control absorption and microRNA/ATP mediated controlled release in cancer, improving the targeting and controllability of the drug carrier can improve the therapeutic effect and reduce the therapeutic effect. Light side effects. We have constructed a multi temperature responsive, intelligent nano carrier with adjustable surface properties for target transport and synchronous controlled release of siRNA and Dox. The PEG shell on the surface of nanoscale effectively prolongs the circulation time of the carrier in the blood, reduces the degradation of the enzymes in the blood and increases the carrier in the tumor part. By passive enrichment of the bit, the specific recognition and absorption of nanoscale in cell and living tumor tissues were realized by near infrared laser control. At the same time, the overexpressed microRNA was selected as the initiator and ATP was a fuel molecule. The synchronous release of siRNA/Dox was realized by triggering the cascade amplification reaction mediated by Toehold, and the therapeutic effect was improved. Fruit can effectively inhibit tumor growth and achieve synergistic treatment.

【學(xué)位授予單位】：南京大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：TB383.1;R730.4

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 孫衍昶;郭t$t$;賽克;王翦;王潔;陳芙蓉;張宗平;陳忠平;;MicroRNA-181b提高U87細(xì)胞對(duì)VM-26的敏感性研究[J];中國神經(jīng)腫瘤雜志;2013年02期

2 汪章勛;周權(quán);孟慧敏;張軍;黃勃;;金龜子綠僵菌MicroRNA在蟬蛻和蠶血淋巴誘導(dǎo)下的差異表達(dá)分析[J];安徽科技學(xué)院學(xué)報(bào);2013年05期

3 Wenwen Jia;Wen Chen;Jiuhong Kang;;The Functions of MicroRNAs and Long Non-coding RNAs in Embryonic and Induced Pluripotent Stem Cells[J];Genomics,Proteomics & Bioinformatics;2013年05期

4 安麗娜;董斐斐;王國坤;單冬凱;荊清;;MicroRNA與動(dòng)脈粥樣硬化[J];國際心血管病雜志;2013年04期

5 馮楠楠;孫品;夏昭林;;凋亡相關(guān)的microRNA分子研究進(jìn)展[J];工業(yè)衛(wèi)生與職業(yè)病;2013年05期

6 陳娟娟;艾劍剛;黃世峰;曹炬;張莉萍;;HBx介導(dǎo)miR-221上調(diào)-ERα下調(diào)致HepG2細(xì)胞惡性增殖[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2013年20期

7 張世芳;魏彩虹;陸健;張小寧;周鑫磊;張淑珍;王光凱;曹家雪;趙福平;張莉;杜立新;;深度測序鑒定綿羊microRNA轉(zhuǎn)錄組[J];中國畜牧獸醫(yī);2013年09期

8 張義;李龍;岳信;田夫;;miRNA與腫瘤的研究進(jìn)展[J];長江大學(xué)學(xué)報(bào)(自科版);2013年36期

9 李劍峰;蔣晨;;腦膠質(zhì)瘤靶向藥物遞送系統(tǒng)[J];國際藥學(xué)研究雜志;2013年05期

10 謝向陽;林雯;李e，

本文編號(hào)：1882944