本文選題：富勒烯 + 四氧化三鐵　； 參考：《鄭州大學(xué)》2014年碩士論文

【摘要】：富勒烯（C60）具有獨特的結(jié)構(gòu)和特殊的光學(xué)性質(zhì)，在藥物轉(zhuǎn)運和腫瘤光動力學(xué)治療方面具有潛在應(yīng)用價值，但其難溶性極大地限制了在生物醫(yī)學(xué)領(lǐng)域中的應(yīng)用。本課題研究目的是對富勒烯進(jìn)行化學(xué)修飾，在其表面連接磁性四氧化三鐵納米粒（IONPs）和親水性基團(tuán)聚乙二醇2000（PEG2000），開發(fā)出新型磁性水溶性藥物轉(zhuǎn)運載體C60-IONP-PEG，并攜帶小分子光敏劑血卟啉單甲醚（HMME），構(gòu)建一個具有良好的磁靶向能力、光療能力和核磁成像能力的多功能腫瘤靶向給藥系統(tǒng)C60-IONP-PEG/HMME。 本課題首先構(gòu)建了基于富勒烯衍生物的藥物載體。利用Bingle環(huán)加成反應(yīng)、酯水解反應(yīng)、水熱化學(xué)鍵合反應(yīng)合成四氧化三鐵負(fù)載的富勒烯（C60-IONP-COOH），利用聚乙二醇2000（PEG(2000)-NH2）的氨基與該富勒烯衍生物的羧基加成，制備出磁性的C60載體系統(tǒng)C60-IONP-PEG。使用傅里葉變換紅外光譜驗證該載體系統(tǒng)制備是否成功，使用透射電子顯微鏡、激光納米粒度分析儀等進(jìn)行形態(tài)表征，，使用振動樣品磁測量儀來檢測磁性，使用熱重分析儀測定該系統(tǒng)中PEG的含量，使用3T核磁共振掃描儀考察該系統(tǒng)核磁成像能力。結(jié)果表明該磁性載體系統(tǒng)制備成功，C60-IONP-PEG具有高度的水溶性、明顯的超順磁性和顯著的核磁成像能力，并且具有合適的粒徑和電位，可作為優(yōu)良的磁靶向藥物轉(zhuǎn)運載體。 在磁靶向納米制劑的制備中，以小分子光敏劑HMME為模型藥物，通過單因素實驗考察HMME與載體材料的投料比、超聲時間、探超功率等因素對制劑載藥量的影響，確定了擬構(gòu)建腫瘤靶向給藥系統(tǒng)C60-IONP-PEG/HMME的最佳處方工藝。使用透射電子顯微鏡、激光納米粒度分析儀和紫外全波長掃描儀對該系統(tǒng)進(jìn)行表征，結(jié)果表明C60-IONP-PEG能夠高效負(fù)載HMME（載藥率~125.3%），構(gòu)建的給藥系統(tǒng)具有良好的穩(wěn)定性和大小均一的粒徑，能夠緩釋藥物，可持續(xù)釋放藥物達(dá)120小時。 在體外抗腫瘤活性評價中，選用鼠源黑色素瘤（B16-F10）細(xì)胞作為研究對象，對HMME和C60協(xié)同增強光動力學(xué)治療腫瘤的作用進(jìn)行了研究，結(jié)果表明空白載體C60-IONP-PEG對B16-F10細(xì)胞無明顯毒性，但在532nm激光照射下能夠高效產(chǎn)生活性氧，可作為光敏劑應(yīng)用于光動力學(xué)治療中。此外，532nm激光照射后，C60-IONP-PEG/HMME體系中的C60和HMME均高效產(chǎn)生活性氧，協(xié)同增強光療作用，共同殺傷腫瘤細(xì)胞，且具有濃度和光照強度依賴性。實驗結(jié)果還表明C60-IONP-PEG/HMME具有良好的磁靶向性，對磁場區(qū)域腫瘤細(xì)胞抑制增殖作用強。細(xì)胞內(nèi)的T2場核磁信號強度隨C60-IONP-PEG濃度的增加而減弱，其核磁成像的圖像呈現(xiàn)明顯的黑化效應(yīng)。 在體內(nèi)光療活性評價中，以接種B16-F10細(xì)胞的C57小鼠為模型動物，分別考察了C60-IONP-PEG/HMME、C60-IONP-PEG、HMME在光照和不光照條件下對小鼠黑色素瘤抑制作用，結(jié)果表明C60-IONP-PEG/HMME在磁場作用下可滯留于腫瘤部位，532nm激光照射后發(fā)揮高效的光療作用，其效果明顯優(yōu)于單純的C60或HMME。此外，C60-IONP-PEG能夠使荷瘤小鼠腫瘤、肝、脾、腎等器官的T2場信號顯著降低，具有良好的負(fù)性增強效果，可作為體內(nèi)核磁成像T2場的造影劑。 以上結(jié)果表明，多功能腫瘤靶向光療系統(tǒng)C60-IONP-PEG/HMME具有良好的磁靶向性、高效的光療活性和卓越的核磁成像能力，在腫瘤診斷和治療中具有潛在的應(yīng)用價值。
[Abstract]:Fullerene (C60), with its unique structure and special optical properties, has potential application value in drug transport and photodynamic therapy, but its insolubility greatly restricts its application in the field of biomedicine. The purpose of this study is to modify the fullerenes and connect magnetic iron oxide to the surface of the fullerenes. Rice grain (IONPs) and hydrophilic group polyethylene glycol 2000 (PEG2000) have developed a new magnetic water soluble drug transport carrier, C60-IONP-PEG, and carry small molecular photosensitizer, porphyrin monomethyl ether (HMME), to construct a multi-functional tumor targeting drug delivery system with good magnetic targeting ability, phototherapy ability and nuclear magnetic imaging ability, C60-IONP-PEG/HMME.
First, a drug carrier based on fullerene derivatives was constructed. The Bingle ring addition reaction, ester hydrolysis reaction, thermochemical bonding reaction were used to synthesize the fullerene (C60-IONP-COOH) loaded with iron oxide, and the magnetic C60 load was prepared by the addition of the amino group of 2000 (PEG (2000) -NH2) with the carboxyl group of the fullerene derivative. The body system C60-IONP-PEG. uses Fourier transform infrared spectroscopy to verify the success of the carrier system, using transmission electron microscope, laser nanoscale analyzer and so on for morphological characterization, using a vibrating sample magnetometer to detect the magnetic properties, using a thermogravimetric analyzer to determine the content of PEG in the system, and using 3T NMR scanner. The results show that the magnetic carrier system is successfully prepared. C60-IONP-PEG has high water solubility, obvious superparamagnetic and significant magnetic imaging ability, and has a suitable particle size and potential. It can be used as a good carrier for magnetic targeting drug delivery.
In the preparation of magnetic targeting nanoscale preparation, using the small molecular photosensitizer HMME as the model drug, the influence of the dosage of HMME and the carrier material, the ultrasonic time and the super power on the dosage of drug delivery was investigated by single factor experiment, and the best prescription technology for the construction of the tumor targeting drug delivery system C60-IONP-PEG/HMME was determined. Transmission electron was used. The system was characterized by microscope, laser nanoscale analyzer and UV full wavelength scanner. The results showed that C60-IONP-PEG could efficiently load HMME (~125.3%). The system had good stability and uniform size, sustained release drug and sustained release of drugs for 120 hours.
In the evaluation of anti tumor activity in vitro, the mouse source melanoma (B16-F10) cells were selected as the research object, and the synergistic effect of HMME and C60 on the photodynamic treatment of the tumor was studied. The results showed that the blank carrier C60-IONP-PEG had no obvious toxicity to B16-F10 cells, but it could produce the living oxygen efficiently under the 532nm laser irradiation. The photosensitizer is used in photodynamic therapy. In addition, after 532nm laser irradiation, both C60 and HMME in the C60-IONP-PEG/HMME system produce the living oxygen efficiently, synergistically enhance the phototherapy effect, kill the tumor cells together, and have the concentration and light intensity dependence. The experimental results also show that C60-IONP-PEG/HMME has good magnetic targeting and magnetic field. Regional tumor cells have a strong inhibitory effect on proliferation. The intensity of nuclear magnetic signal in T2 field decreases with the increase of C60-IONP-PEG concentration, and the image of NMR imaging shows obvious blackening effect.
In the evaluation of phototherapy activity in vivo, C57 mice inoculated with B16-F10 cells were used as model animals. The inhibitory effects of C60-IONP-PEG/HMME, C60-IONP-PEG and HMME on the melanoma of mice under light and light conditions were investigated. The results showed that C60-IONP-PEG/HMME could be retained at the tumor site under the effect of magnetic field, and 532nm laser irradiated high efficiency. The effect of phototherapy is obviously better than that of simple C60 or HMME.. C60-IONP-PEG can significantly reduce the T2 field signal of tumor, liver, spleen and kidney in tumor bearing mice. It has a good negative enhancement effect and can be used as a contrast agent in the T2 field of MRI in vivo.
The above results show that the multi-functional tumor targeted phototherapy system C60-IONP-PEG/HMME has good magnetic targeting, high effective phototherapy activity and excellent magnetic imaging ability, and has potential application value in the diagnosis and treatment of tumor.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R943

【參考文獻(xiàn)】

相關(guān)期刊論文 前8條

1 丁漣沭,徐如祥,楊志林;腫瘤光動力學(xué)治療[J];中華神經(jīng)醫(yī)學(xué)雜志;2005年11期

2 劉佳雯;楊玉強;張治國;;激光光動力學(xué)治療癌癥的新進(jìn)展[J];哈爾濱工業(yè)大學(xué)學(xué)報;2006年03期

3 王玲昀;陳秋云;魏斌;;腫瘤診斷的MRI造影劑[J];化學(xué)進(jìn)展;2010年01期

4 嚴(yán)慶豐,錢凱先,李文鑄;C_(60)對DNA光動力學(xué)作用的FT-Raman光譜研究[J];中國激光;1998年07期

5 顧瑛,劉凡光,王開,朱建國,梁潔,潘玉明,李峻亨;光動力療法治療鮮紅斑痣1216例臨床分析[J];中國激光醫(yī)學(xué)雜志;2001年02期

6 宋坤;孔北華;曲訊;李莉;王文霞;楊興升;張友忠;王波;姜潔;崔保霞;王立杰;;血卟啉單甲醚用于卵巢上皮性癌光動力學(xué)治療的實驗研究[J];中華婦產(chǎn)科雜志;2006年05期

7 李昕;李偉;;光動力學(xué)治療皮膚相關(guān)疾病的研究進(jìn)展[J];組織工程與重建外科雜志;2012年02期

8 劉健;郝倩云;趙雪松;劉婉華;;用光譜法研究光敏劑血卟啉單甲醚對腫瘤細(xì)胞光動力作用的分子機制[J];應(yīng)用激光;2012年02期

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