本文選題：碳納米管 + 透明質(zhì)酸��； 參考：《鄭州大學》2014年碩士論文

【摘要】：碳納米管具有良好的細胞膜穿透性，并且可通過吸附、化學偶聯(lián)或者包合作用攜帶化學藥物或者生物大分子穿過細胞膜，進入細胞或組織，在傳遞藥物方面有著潛在的優(yōu)勢。然而，未加修飾的碳納米管表面疏水性強，在細胞中易聚集，毒性較大，，不適合作為藥物載體。本課題旨在通過表面共價修飾的方法，將磁性Fe3O4納米粒和具有腫瘤靶向性和親水性的透明質(zhì)酸多糖接枝到碳納米管上，得到一種高水溶性、低毒性的磁性碳納米管，通過物理吸附（π-π）堆積的作用裝載化療藥物多西他賽（Docetaxel，DTX），構(gòu)建一個水溶性良好的磁靶向給藥系統(tǒng)，并以人乳腺癌MCF-7細胞和S180肉瘤荷瘤小鼠為對象考察其體內(nèi)外抗腫瘤活性。 首先，通過一系列的羧基化、氨基化以及還原反應(yīng)，將Fe3O4納米粒負載到碳納米管上，得到超順磁性的碳納米管，再通過酯化反應(yīng)將分子量14000~20000的透明質(zhì)酸接枝到碳納米管表面，得到水溶性、形態(tài)、粒徑、電位均良好的磁性碳納米管（CNTs-Fe3O4-HA）。并通過傅里葉變換紅外光譜(FT-IR)、激光納米粒度分析儀(DLS)、振動樣品磁強計（VSM）以及透射電子顯微鏡（TEM）等對其合成過程及磁性行為進行表征，結(jié)果表明載體系統(tǒng)制備成功且具有良好的超順磁性。 其次，以合成的CNTs-Fe3O4-HA為載體，DTX為模型藥物，通過物理吸附π-π堆積的作用構(gòu)建CNTs-Fe3O4-HA/DTX給藥系統(tǒng)，通過單因素考察優(yōu)化處方設(shè)計，所得的CNTs-Fe3O4-HA/DTX給藥系統(tǒng)載藥率高達160%，所得制劑藥物濃度高達2.3mg·ml-1，其在各個介質(zhì)中可長期穩(wěn)定存在，具有作為納米給藥系統(tǒng)的潛力。 本研究以人乳腺癌MCF-7細胞為實驗對象考察該給藥系統(tǒng)的體外抗腫瘤活性。細胞毒性實驗表明CNTs-Fe3O4-HA對細胞無明顯毒性，而與DTX相比，CNTs-Fe3O4-HA/DTX在作用時間為72h時表現(xiàn)出較強的細胞抑制，表明該給藥系統(tǒng)具有一定的緩釋作用。細胞攝取實驗表明CNTs-Fe3O4-HA可高效率的穿透細胞膜，促進了DTX的跨膜轉(zhuǎn)運。 此外，以S180肉瘤荷瘤小鼠為模型動物，考察CNTs-Fe3O4-HA/DTX給藥系統(tǒng)的組織分布以及體內(nèi)抗腫瘤活性。組織分布實驗表明，CNTs-Fe3O4-HA可提高藥物在腫瘤部位的濃集，降低DTX的肺毒性，且在外加磁場作用下長期連續(xù)給藥后可有效提藥物在腫瘤部位的濃度，降低DTX在肺中的分布，且在外加磁場作用下長期連續(xù)給藥后可顯著提高藥物在腫瘤部位的分布，該結(jié)果表明，CNTs-Fe3O4-HA/DTX在體內(nèi)具有顯著的磁靶向能力。體內(nèi)抗腫瘤實驗表明，CNTs-Fe3O4-HA/DTX給藥系統(tǒng)提高了DTX的抗腫瘤活性，且在外加磁場作用下，CNTs-Fe3O4-HA/DTX給藥系統(tǒng)對腫瘤體積的增長抑制更加明顯。
[Abstract]:Carbon nanotubes (CNTs) have good cell membrane penetration and have potential advantages in drug delivery by means of adsorption, chemical coupling or inclusion cooperation through cell membranes or biological macromolecules carrying chemical drugs or biological macromolecules. However, unmodified carbon nanotubes have strong hydrophobicity, easy aggregation and toxicity in cells, so they are not suitable as drug carriers. The aim of this study was to graft magnetic Fe3O4 nanoparticles and hyaluronic acid polysaccharides with tumor targeting and hydrophilicity onto carbon nanotubes by surface covalent modification to obtain a highly water-soluble and low-toxic magnetic carbon nanotubes. The chemotherapeutic drug docetaxelon DTX was loaded by physical adsorption (蟺-蟺) to construct a water-soluble magnetic targeting drug delivery system. The antitumor activity of human breast cancer MCF-7 cells and S180 sarcoma bearing mice was investigated in vitro and in vivo. First, the superparamagnetic carbon nanotubes were prepared by loading Fe3O4 nanoparticles onto carbon nanotubes through a series of carboxylation, amination and reduction reactions, and then grafted hyaluronic acid with molecular weight 14000,000000 onto the surface of carbon nanotubes by esterification. A magnetic carbon nanotube CNTs-Fe _ 3O _ 4-HAN _ 4 with good water solubility, morphology, particle size and potential was obtained. The synthesis process and magnetic behavior were characterized by Fourier transform infrared spectroscopy (FTIR), laser nanocrystalline analyzer (DLSX), vibrating sample magnetometer (VSM) and transmission electron microscope (TEM). The results showed that the carrier system was successfully prepared and had good superparamagnetic properties. Secondly, the drug delivery system of CNTs-Fe3O4-HA was constructed by physical adsorption of 蟺-蟺 accumulation, and the prescription design was optimized by single factor investigation. The drug loading rate of the CNTs-Fe3O4-HA/DTX drug delivery system is as high as 160 and the drug concentration of the preparation is as high as 2.3mg ml-1, which can exist in various media for a long time and has the potential as a nanometer drug delivery system. In this study, human breast cancer MCF-7 cells were used to investigate the antitumor activity of the drug delivery system in vitro. The cytotoxicity test showed that CNTs-Fe3O4-HA had no obvious cytotoxicity, but CNTs-Fe3O4-HA / DTX exhibited strong cell inhibition at 72 h compared with DTX, indicating that the drug delivery system had a certain sustained release effect. Cell uptake assay showed that CNTs-Fe3O4-HA could penetrate the cell membrane efficiently and promote the transmembrane transport of DTX. In addition, S180 sarcoma bearing mice were used as model animals to investigate the tissue distribution and antitumor activity of CNTs-Fe3O4-HA/DTX delivery system. The results of tissue distribution showed that CNTs-Fe _ 3O _ 4-HA could increase the concentration of DTX in the tumor site and decrease the pulmonary toxicity of DTX. The concentration of CNTs-Fe _ 3O _ 4-HA in the tumor site and the distribution of DTX in lung could be effectively extracted after long-term continuous administration under the action of external magnetic field. The results showed that CNTs-Fe _ 3O _ 4-HA / DTX had significant magnetic targeting ability in vivo. In vivo antitumor experiments showed that CNTs-Fe3O4-HA / DTX administration system increased the antitumor activity of DTX, and CNTs-Fe3O4-HA / DTX system inhibited tumor volume more obviously under the action of external magnetic field.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R943

【參考文獻】

相關(guān)期刊論文 前3條

1 萬謨彬;汪偉業(yè);秦一中;;透明質(zhì)酸在肝臟內(nèi)的代謝及其臨床意義[J];國外醫(yī)學.流行病學傳染病學分冊;1990年03期

2 黃銀久;宋寶安;金林紅;胡德禹;楊松;李寧;吳守偉;;SRB法和MTT法抗腫瘤藥物篩選結(jié)果相關(guān)性研究[J];生物學雜志;2009年04期

3 ;FT-IR Study of Carbon Nanotube Supported Co-Mo Catalysts[J];Journal of Natural Gas Chemistry;2004年02期

本文編號：1830459