發(fā)布時間：2018-06-16 11:42

  本文選題：納米金剛石 + 表面修飾　； 參考：《吉林大學(xué)》2014年博士論文

【摘要】：納米金剛石具有非常優(yōu)異的物理、化學(xué)特性，特別是其生物相容性及功能化可修飾性，使納米金剛石在生物、醫(yī)學(xué)等諸多領(lǐng)域具有非常重要的研究價值和應(yīng)用前景。納米金剛石的引入，可以提高載藥效果，并應(yīng)用于多種腫瘤細(xì)胞的化療。進(jìn)一步拓展納米金剛石對不同藥物的載藥及提高藥物的治療效果，成為近年來納米材料在生物醫(yī)學(xué)研究領(lǐng)域的重要前沿課題。本論文以爆炸法納米金剛石(DND)為基礎(chǔ)，通過表面功能化，連接全反式維甲酸(ATRA)，研究其在人早幼粒白血病細(xì)胞(HL-60細(xì)胞)凋亡過程中的促進(jìn)作用。主要研究內(nèi)容和結(jié)果如下： 1.采用超聲、高溫等處理過程，通過相轉(zhuǎn)變和氧化反應(yīng)，，以及醇分子與納米金剛石液相化學(xué)反應(yīng)，對平均粒度約5nm的爆炸法納米金剛石(DND)進(jìn)行顆粒分散。實(shí)驗(yàn)表明，相對于其他方法，液相反應(yīng)使納米金剛石表面修飾了酯類化學(xué)基團(tuán)，基本呈單分散狀態(tài)。 2.將用于治療急性早幼粒白血病(APL)的ATRA藥物與單分散的表面修飾納米金剛石顆粒相結(jié)合，納米金剛石表面修飾的酯類基團(tuán)的疏水性有利于ATRA的碳環(huán)端與納米金剛石修飾表面之間的吸附結(jié)合，制備了DND-ATRA納米復(fù)合物，通過傅立葉變換紅外光譜、紫外-可見熒光光譜和透射電子顯微鏡等測量，證明了ATRA和納米金剛石有效地組裝在一起，可用于提高ATRA有效濃度和利用率。 3.利用四甲基偶氮唑藍(lán)比色法(MTT)、流式細(xì)胞儀檢測(FACS)及原位末端標(biāo)記(TUNEL)熒光鏡檢等檢測方法，我們系統(tǒng)研究了DND-ATRA納米復(fù)合藥物對人早幼粒白血病細(xì)胞HL-60細(xì)胞的體外促凋亡作用。DND-ATRA復(fù)合物作用2天后，MTT結(jié)果顯示HL-60細(xì)胞的抑制率與單獨(dú)使用ATRA相比提高了38%，并且在8天藥物作用后，DND-ATRA納米復(fù)合物實(shí)驗(yàn)組達(dá)到93%的HL-60有效的凋亡率。與常規(guī)的單獨(dú)ATRA或者其他ATRA-化療藥物作用方式相比，DND-ATRA納米復(fù)合物體系不僅保持了ATRA本身誘導(dǎo)分化癌細(xì)胞的藥物活性，而且更有效地促進(jìn)了HL-60癌細(xì)胞凋亡，較ATRA的細(xì)胞凋亡率提高了35%，細(xì)胞水平上證明了DND-ATRA納米復(fù)合物的有效性，同時說明，納米金剛石是優(yōu)秀的生物相容性載體，可抑制細(xì)胞膜轉(zhuǎn)運(yùn)蛋白對藥物分子的外排效應(yīng)，并對細(xì)胞沒有破壞作用。我們認(rèn)為單純ATRA的代謝形式為胞內(nèi)直接擴(kuò)散，易于降解和清除，而納米復(fù)合物具有細(xì)胞局部區(qū)域擴(kuò)散累積效應(yīng)，可比單獨(dú)ATRA能更持久地誘導(dǎo)HL-60細(xì)胞分化凋亡。 本論文研究表明，DND-ATRA的納米復(fù)合物可以成為高效治療人早幼粒白血病的潛力的藥劑，證明了以納米金剛石為基礎(chǔ)，所構(gòu)建的新型藥物輸送體系具有很好的可行性和實(shí)用性，為今后的動物實(shí)驗(yàn)以及納米金剛石藥物輸送載體對各種功能基團(tuán)和藥物分子的負(fù)載，提供了一定的實(shí)驗(yàn)數(shù)據(jù)和工作基礎(chǔ)，具有潛在的臨床應(yīng)用意義。
[Abstract]:Nano diamond has very excellent physical and chemical properties, especially its biocompatibility and functionalization modifiable, which makes nano diamond have very important research value and application prospect in many fields, such as biology, medicine and so on. The introduction of nano diamond can improve the effect of drug carrying and apply to chemotherapy of various tumor cells. One step to expand the effect of nano diamond on drug loading and drug treatment has become an important frontier topic in the biomedical research field in recent years. This paper, based on the nano diamond (DND), is based on the surface functionalization and connection of all trans retinoic acid (ATRA) to study its fine promyelocytic leukemia. The promoting effect of cell (HL-60 cell) in the process of apoptosis. The main contents and results are as follows:
1. in the process of ultrasonic and high temperature treatment, by phase transition and oxidation reaction, and the chemical reaction between alcohol molecules and nano diamond liquid, the particle dispersion of the nano diamond (DND) with an average particle size of 5nm is dispersed. The experiment shows that the liquid phase reaction makes the nano diamond surface modified with the chemical groups of the esters relative to the other methods. It is monodisperse.
2. the ATRA drugs used in the treatment of acute promyelocytic leukemia (APL) were combined with monodisperse surface modified nano diamond particles. The hydrophobicity of the nano diamond surface modified ester groups was beneficial to the adsorption of the carbon ring ends of ATRA and the nano diamond modified surface. The DND-ATRA nanocomposites were prepared by Fu Liye change. Infrared spectroscopy, ultraviolet visible fluorescence and transmission electron microscopy have proved that ATRA and nano diamond are effectively assembled together, which can be used to improve the effective concentration and utilization of ATRA.
3. using four methyl azolazolium Colorimetry (MTT), flow cytometer detection (FACS) and in situ terminal labeling (TUNEL) fluoroscopy, we systematically studied the effect of DND-ATRA nanocomposite on the apoptosis of HL-60 cells of human promyelocytic leukemia cells in vitro for 2 days, and MTT results showed HL-60 cells. The inhibition rate increased by 38% compared with the single use of ATRA, and after 8 days of drug action, the DND-ATRA nanocomposite experimental group reached 93% of the effective apoptosis rate of HL-60. Compared with the conventional single ATRA or other ATRA- chemotherapeutic agents, the DND-ATRA nanocomposite system did not only maintain the drug of ATRA itself to induce the differentiation of cancer cells. Activity, and more effective to promote the apoptosis of HL-60 cancer cells, increased the apoptosis rate of ATRA by 35%. The cell level proved the effectiveness of DND-ATRA nanocomposites. At the same time, the nano diamond is an excellent biocompatibility carrier, which can inhibit the efflux of cell membrane transporter to drug molecules and not to cells. We think that the metabolic form of simple ATRA is intracellular direct diffusion, which is easy to degrade and clear, and the nanocomposite has the effect of local area diffusion accumulation, which can induce HL-60 cells to differentiate and apoptosis more consistently than single ATRA.
This study shows that DND-ATRA nanocomposite can be a potent agent for the treatment of human promyelocytic leukemia. It is proved that the new drug delivery system based on nano diamond has good feasibility and practicability. It can be used for the future animal experiment and the carrier of nano diamond drug delivery. The loading of energy groups and drug molecules provides certain experimental data and work basis, which has potential clinical application significance.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：TB383.1;R943;R96

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

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2 陳竺,陳賽娟;維甲酸誘導(dǎo)早幼粒白血病細(xì)胞分化的分子機(jī)制研究[J];中國科學(xué)基金;1994年02期

本文編號：2026533