發(fā)布時(shí)間：2018-05-25 20:00

  本文選題：稀土上轉(zhuǎn)換發(fā)光納米材料 + 表面修飾　； 參考：《蘇州大學(xué)》2016年碩士論文

【摘要】：第一部分用于多模成像的稀土上轉(zhuǎn)換發(fā)光納米復(fù)合材料的制備及應(yīng)用初步探究目的:探討稀土上轉(zhuǎn)換發(fā)光納米復(fù)合材料PEDOT:UCNP:Fe_3O_4:PEG用于多模成像應(yīng)用的可行性及價(jià)值。方法:1)采用高溫?zé)岱纸夥ㄖ苽涑錾限D(zhuǎn)換納米顆粒Na YF4(Y:Yb:Er=78%:20%:2%),利用OA-PAA高分子聚合物修飾納米粒子增加其水溶性;以聚(3,4-亞乙二氧基噻吩)-聚(苯乙烯磺酸)(PEDOT:PSS)為核心,外層包裹由OA-PAA修飾的稀土上轉(zhuǎn)換發(fā)光納米材料(UCNPs)及二巰基丁二酸(DMSA)修飾的四氧化三鐵(Fe_3O_4),再通過(guò)層層組裝的方式將納米粒子表面修飾聚丙烯酸(PAA)、多環(huán)芳烴(PAH)及聚乙二醇(PEG)層,最后得到有良好生物相容性的PEDOT:UCNP:Fe_3O_4:PEG上轉(zhuǎn)換發(fā)光納米復(fù)合物,并對(duì)其形貌、電位進(jìn)行表征研究。2)將不同濃度梯度的PEDOT:UCNP:Fe_3O_4:PEG進(jìn)行磁共振T2序列的掃描,檢測(cè)其磁共振成像性質(zhì)。3)取三組梯度濃度的PEDOT:UCNP:Fe_3O_4:PEG溶液及去離子水各1ml,在808nm激光器下照射5分鐘,使用熱成像儀記錄溫度變化,檢測(cè)其光熱效果;4)通過(guò)體外細(xì)胞毒性試驗(yàn)(MTT)對(duì)PEDOT:UCNP:Fe_3O_4:PEG顆粒的體外毒性進(jìn)行研究。5)將PEDOT:UCNP:Fe_3O_4:PEG瘤內(nèi)注入荷瘤小鼠模型,進(jìn)行磁共振T2序列的掃描,檢測(cè)其磁共振成像性質(zhì)。6)將PEDOT:UCNP:Fe_3O_4:PEG孵育小鼠小鼠乳腺癌(4T1)細(xì)胞24小時(shí)后,用DAPI染細(xì)胞核,用熒光顯微鏡觀查PEDOT:UCNP:Fe_3O_4:PEG在細(xì)胞水平成像能力。7)將PEDOT:UCNP:Fe_3O_4:PEG溶液瘤內(nèi)注入荷瘤小鼠模型,用帶有980nm激發(fā)光源的Maestro EX(CRi.Inc.)活體成像系統(tǒng)檢測(cè)其上轉(zhuǎn)換成像性質(zhì)結(jié)果:1)透射電子顯微鏡(TEM)顯示,上轉(zhuǎn)換發(fā)光納米顆粒(UCNPs)是平均直徑約在30nm的單分散納米晶體。經(jīng)過(guò)組裝和層層修飾以后,PEDOT:UCNP:Fe_3O_4:PEG上轉(zhuǎn)換發(fā)光納米復(fù)合物在水溶液中具有較好的穩(wěn)定性,能在各種溶液中長(zhǎng)時(shí)間穩(wěn)定存在;制備好的PEDOT:UCNP:Fe_3O_4:PEG溶液電位接近0;2)磁共振成像結(jié)果顯示在一定的濃度梯度內(nèi),隨著材料濃度的增加,PEDOT:UCNP:Fe_3O_4:PEG溶液的磁共振信號(hào)逐漸降低。3)PEDOT:UCNP:Fe_3O_4:PEG在體外具有強(qiáng)大的光熱能力;4)體外細(xì)胞毒性實(shí)驗(yàn)結(jié)果顯示PEDOT:UCNP:Fe_3O_4:PEG在較高濃度時(shí)對(duì)細(xì)胞亦未見(jiàn)明顯毒性作用。5)對(duì)比上轉(zhuǎn)換發(fā)光納米材料在瘤內(nèi)注射前后的T2 WI圖片,可見(jiàn)在瘤內(nèi)注入PEDOT:UCNP:Fe_3O_4:PEG溶液后腫瘤部位T2信號(hào)明顯降低,腫瘤包膜完整,PEDOT:UCNP:Fe_3O_4:PEG溶液在瘤內(nèi)分布均勻;6)在PEDOT:UCNP:Fe_3O_4:PEG溶液孵育4T1細(xì)胞24小時(shí)后,共聚焦顯微鏡下可見(jiàn)大量上轉(zhuǎn)換發(fā)光顆粒在細(xì)胞內(nèi)富集;7)瘤內(nèi)注入PEDOT:UCNP:Fe_3O_4:PEG之后,在近紅外光激發(fā)下,腫瘤部位可見(jiàn)明顯綠色熒光;結(jié)論:PEDOT:UCNP:Fe_3O_4:PEG納米材料可以在各種溶液中穩(wěn)定存在,展現(xiàn)出極好的穩(wěn)定性。細(xì)胞增殖實(shí)驗(yàn)結(jié)果表明,PEDOT:UCNP:Fe_3O_4:PEG復(fù)合物沒(méi)有明顯的生物毒性。同時(shí)具有較好的磁共振成像能力。近紅外光照射下,由于PEDOT:UCNP:Fe_3O_4:PEG所具有的獨(dú)特的上轉(zhuǎn)換發(fā)光能力,可以作為上轉(zhuǎn)換光學(xué)成像的探針;同時(shí),PEDOT:UCNP:Fe_3O_4:PEG也是一種高效的光熱介質(zhì)。因此,PEDOT:UCNP:Fe_3O_4:PEG納米復(fù)合材料可以用于腫瘤的多模成像,在腫瘤的光熱治療方面也有巨大的潛力。第二部分稀土上轉(zhuǎn)換發(fā)光納米復(fù)合材料用于腫瘤的光熱治療的研究目的:稀土上轉(zhuǎn)換發(fā)光納米復(fù)合材料用于腫瘤的光熱治療的研究。方法:1)將同濃度的PEDOT:UCNP:Fe_3O_4:PEG溶液孵育小鼠乳腺癌(4T1)細(xì)胞6小時(shí)后,用梯度功率的近紅外光(808nm)照射5分鐘后,培養(yǎng)24小時(shí)后用MTT法測(cè)定細(xì)胞存活率。2)將小鼠乳腺癌(4T1)細(xì)胞在小鼠背部皮下注射建立荷瘤小鼠模型。3)將荷瘤小鼠隨機(jī)分為四組,治療前測(cè)量瘤體。實(shí)驗(yàn)組(d組)予以PEDOT:UCNP:Fe_3O_4:PEG瘤內(nèi)注射及激光照射;對(duì)照組中,a組予以等量生理鹽水瘤內(nèi)注射,b組僅予以PEDOT:UCNP:Fe_3O_4:PEG瘤內(nèi)注射,c組予以生理鹽水瘤內(nèi)注射及激光照射。治療后每?jī)商鞙y(cè)量瘤體大小,比較不同組間瘤體變化,評(píng)估治療效果。4)實(shí)驗(yàn)進(jìn)行過(guò)程中,每天觀察動(dòng)物活動(dòng)、進(jìn)食、排便及精神狀態(tài);實(shí)驗(yàn)完成后,取各組實(shí)驗(yàn)小鼠的主要器官,通過(guò)HE染色行組織學(xué)檢查,評(píng)估納米材料毒性。結(jié)果:1)在808nm激光照射下,在激光功率達(dá)到1W/cm2,基本無(wú)細(xì)胞存活,在細(xì)胞水平顯示出良好的光熱治療效果。2)荷瘤小鼠模型在一周內(nèi)建立完成。3)在經(jīng)過(guò)光熱治療后,實(shí)驗(yàn)組小鼠腫瘤在一天后完全消失,60天內(nèi)無(wú)小鼠死亡及腫瘤復(fù)發(fā);其余對(duì)照組腫瘤持續(xù)生長(zhǎng),并都在60天內(nèi)死亡;4)在實(shí)驗(yàn)過(guò)程中,實(shí)驗(yàn)小鼠無(wú)異常行為及死亡,實(shí)驗(yàn)完成后各組小鼠主要器官的組織學(xué)檢查無(wú)明顯異常。結(jié)論:PEDOT:UCNP:Fe_3O_4:PEG在細(xì)胞水平光熱治療中展現(xiàn)出出色的治療效果,在活體光熱治療試驗(yàn)中,PEDOT:UCNP:Fe_3O_4:PEG納米復(fù)合材料未顯示出明顯毒性并展現(xiàn)出極好的療效。所以PEDOT:UCNP:Fe_3O_4:PEG上轉(zhuǎn)換發(fā)光納米復(fù)合物可以作為腫瘤多模成像并指導(dǎo)治療的介質(zhì)。
[Abstract]:The first part is the preparation and application of rare earth up-conversion luminescent nanocomposites for multimode imaging. The purpose of this study is to explore the feasibility and value of the use of rare-earth upconversion luminescent nanocomposite PEDOT:UCNP:Fe_3O_4:PEG for multimode imaging. Method: 1) up conversion nano particles Na YF4 (Y:Yb:Er) was prepared by high temperature thermal decomposition method. =78%: 20%: 2%) the water solubility of the nanoparticles was added with the OA-PAA polymer modified nanoparticles; the core (3,4- subethoxy thiophene) - polyphenols (PEDOT:PSS) was used as the core, and the outer layer was coated with OA-PAA modified rare earth upconversion luminescent nanomaterials (UCNPs) and two mercapto acid (DMSA) modified iron oxide (Fe_3O_4), and then through the layer. The surface of the nano particles is modified by the coating of polyacrylic acid (PAA), polycyclic aromatic hydrocarbons (PAH) and polyethylene glycol (PEG) layer. Finally, the PEDOT:UCNP:Fe_3O_4:PEG upconversion nanocomposites with good biocompatibility are obtained, and the morphology and potential of the.2 are investigated. The PEDOT:UCNP:Fe_3O_4:PEG of different concentration gradient is magnetically shared. The scanning of the vibrating T2 sequence, detecting its magnetic resonance imaging properties.3) take three groups of gradient concentration PEDOT:UCNP:Fe_3O_4:PEG solution and deionized water each 1ml, irradiate the 808nm laser for 5 minutes, use the thermal imager to record the temperature change, and detect its photothermal effect; 4) through the in vitro cytotoxicity test (MTT) on the PEDOT:UCNP:Fe_3O_4:PEG granules in vitro Toxicity study.5) injected PEDOT:UCNP:Fe_3O_4:PEG tumor into the tumor bearing mouse model, scanned the magnetic resonance T2 sequence and detected its magnetic resonance imaging properties.6). After 24 hours of incubating the breast cancer (4T1) cells in mice, PEDOT:UCNP:Fe_3O_4:PEG was used to dye the nucleus with DAPI, and the level of PEDOT:UCNP:Fe_3O_4:PEG at the cell level was examined by the fluorescence microscope. Imaging ability.7) injected the PEDOT:UCNP:Fe_3O_4:PEG solution tumor into the tumor bearing mouse model and detected its upconversion imaging properties with the Maestro EX (CRi.Inc.) living imaging system with 980nm excitation light source: 1) transmission electron microscopy (TEM) showed that the upconversion luminescent nanoparticles (UCNPs) were mono dispersed nanocrystals with an average diameter of about 30nm. After the assembly and layer modification, the PEDOT:UCNP:Fe_3O_4:PEG upconversion nanocomposites have good stability in the aqueous solution and can exist for a long time in various solutions; the prepared PEDOT:UCNP:Fe_3O_4:PEG solution potential is close to 0; 2) the magnetic resonance imaging results show in a certain concentration gradient with the concentration of the material. In addition, the magnetic resonance signal of PEDOT:UCNP:Fe_3O_4:PEG solution gradually decreased.3) PEDOT:UCNP:Fe_3O_4:PEG has a strong photothermal ability in vitro; 4) in vitro cytotoxicity test results showed that PEDOT:UCNP:Fe_3O_4:PEG had no obvious toxic effect on the cells at high concentration.5) compared with the upconversion luminescent nanomaterials before intratumoral injection. After the injection of PEDOT:UCNP:Fe_3O_4:PEG solution in the T2 WI picture, the T2 signal of the tumor site was obviously reduced, the tumor envelope was complete and the PEDOT:UCNP:Fe_3O_4:PEG solution was evenly distributed in the tumor. 6) after incubating 4T1 cells in PEDOT:UCNP:Fe_3O_4:PEG solution for 24 hours, a large number of upconversion luminescent particles were found in the cell under confocal microscopy. Enrichment; 7) after intratumoral injection of PEDOT:UCNP:Fe_3O_4:PEG, the tumor site was obviously green fluorescence under near infrared light excitation. Conclusion: PEDOT:UCNP:Fe_3O_4:PEG nano materials can be stable in various solutions and exhibit excellent stability. The results of cell proliferation experiment show that the PEDOT:UCNP:Fe_3O_4:PEG complex has no obvious birth. At the same time, it has good magnetic resonance imaging ability. Under the near infrared radiation, the unique upconversion luminescence ability of PEDOT:UCNP:Fe_3O_4:PEG can be used as a probe for upconversion optical imaging. At the same time, PEDOT:UCNP:Fe_3O_4:PEG is also an efficient photothermal medium. Therefore, PEDOT:UCNP:Fe_3O_4:PEG nanocomposites are used. The multimode imaging of tumors can also have great potential in the photothermal treatment of tumors. Second parts of the rare earth upconversion luminescent nanocomposites are used for the photothermal treatment of tumors. The rare earth upconversion luminescent nanocomposites are used to study the photothermal treatment of tumors. Method: 1) the same concentration of PEDOT:UCNP:Fe_3O_4: The mice breast cancer (4T1) cells were incubated with PEG solution for 6 hours. After 5 minutes of irradiation with gradient power of near infrared light (808nm), the cell survival rate was determined by MTT method for 24 hours. The mice breast cancer (4T1) cells were injected subcutaneously in the mouse back to establish the tumor bearing mouse model.3). The tumor bearing mice were randomly divided into four groups, and the tumor body was measured before treatment. The group (Group D) was given PEDOT:UCNP:Fe_3O_4:PEG intratumoral injection and laser irradiation; in the control group, group A was given intratumoral injection of equal amount of saline, group B was injected only with PEDOT:UCNP:Fe_3O_4:PEG intratumoral injection, group C was injected with intratumoral injection of saline and laser irradiation. After treatment, the size of tumor body was measured every two days, and the changes of different groups of tumor bodies were compared and the treatment of treatment was evaluated. .4) during the experiment, we observed animal activities, feeding, defecation and mental state every day. After the experiment, the main organs of the mice were taken and the toxicity of nanomaterials was evaluated through HE staining. Results: 1) the laser power reached 1W/cm2 under the 808nm laser irradiation, and the cell level was basically no cell survival. The mice model of tumor bearing mice was set up to complete.3 in one week. After photothermal treatment, the tumor of mice in the experimental group disappeared completely after one day, and no mice died and the tumor recurred within 60 days. The other control groups continued to grow, and all died within 60 days, and 4) in the course of the experiment, the experimental mice had no abnormal action. There were no obvious abnormalities in the histological examination of the main organs of each group after the experiment. Conclusion: PEDOT:UCNP:Fe_3O_4:PEG showed excellent therapeutic effect in the treatment of cell level photothermal treatment. In vivo photothermal therapy, PEDOT:UCNP:Fe_3O_4:PEG nanocomposite did not show obvious toxicity and showed excellent efficacy. Therefore, the PEDOT:UCNP:Fe_3O_4:PEG upconversion luminescent nanocomposite can be used as a multi-mode imaging and guiding medium for tumor therapy.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R73-3

【相似文獻(xiàn)】

相關(guān)期刊論文 前2條

1 王丹;錢駿;何賽靈;;摻Gd上轉(zhuǎn)換發(fā)光納米棒的細(xì)胞成像應(yīng)用[J];科學(xué)通報(bào);2013年07期

2 ;[J];;年期

相關(guān)會(huì)議論文 前10條

1 徐莉;關(guān)彩虹;于孟斌;金亮;陳高云;;上轉(zhuǎn)換發(fā)光技術(shù)在生化快速檢測(cè)中的應(yīng)用研究[A];公共安全中的化學(xué)問(wèn)題研究進(jìn)展（第二卷）[C];2011年

2 陳大欽;王元生;余運(yùn)龍;劉鋒;黃萍;;釹摻雜的納米結(jié)構(gòu)玻璃陶瓷的紅外激發(fā)紫外上轉(zhuǎn)換發(fā)光[A];第11屆全國(guó)發(fā)光學(xué)學(xué)術(shù)會(huì)議論文摘要集[C];2007年

3 冷雪松;徐玉恒;;三摻Nd:Yb:Ho:LiNbO_3中的能量上轉(zhuǎn)煥發(fā)光[A];第十六屆全國(guó)晶體生長(zhǎng)與材料學(xué)術(shù)會(huì)議論文集-03激光和非線性光學(xué)晶體[C];2012年

4 劉熠;劉倩;馮瑋;李富友;;上轉(zhuǎn)換發(fā)光生物成像技術(shù)及應(yīng)用研究[A];第八屆全國(guó)化學(xué)生物學(xué)學(xué)術(shù)會(huì)議論文摘要集[C];2013年

5 鄒先梅;劉熠;朱幸俊;姚立明;馮瑋;李富友;;808nm激發(fā)的上轉(zhuǎn)換發(fā)光納米復(fù)合探針用于次氯酸的檢測(cè)[A];中國(guó)化學(xué)會(huì)第29屆學(xué)術(shù)年會(huì)摘要集——第33分會(huì)：納米材料合成與組裝[C];2014年

6 趙謖玲;侯延冰;徐敘tb;;不同基質(zhì)材料中鉺離子的上轉(zhuǎn)換發(fā)光特性[A];第九屆全國(guó)發(fā)光學(xué)術(shù)會(huì)議摘要集[C];2001年

7 潘秀紅;;懸浮技術(shù)制備稀土摻雜鈦酸鹽玻璃及其上轉(zhuǎn)換發(fā)光性能[A];中國(guó)空間科學(xué)學(xué)會(huì)空間材料專業(yè)委員會(huì)2011學(xué)術(shù)交流會(huì)論文集[C];2011年

8 高偉;李嬌;涂銀勛;高當(dāng)麗;田宇;鄭海榮;;水熱合成六方相NaYbF4:Pr3+晶體上轉(zhuǎn)換發(fā)光特性研究[A];2011西部光子學(xué)學(xué)術(shù)會(huì)議論文摘要集[C];2011年

9 朱幸俊;李富友;;多功能稀土上轉(zhuǎn)換發(fā)光納米復(fù)合結(jié)構(gòu)用于小動(dòng)物多模式成像[A];中國(guó)化學(xué)會(huì)第29屆學(xué)術(shù)年會(huì)摘要集——第05分會(huì)：無(wú)機(jī)化學(xué)[C];2014年

10 董浩;王也夫;李洋;張超;孫聆東;嚴(yán)純?nèi)A;;稀土離子上轉(zhuǎn)換發(fā)光的調(diào)控及其光敏應(yīng)用[A];中國(guó)化學(xué)會(huì)第29屆學(xué)術(shù)年會(huì)摘要集——第06分會(huì)：稀土材料化學(xué)及應(yīng)用[C];2014年

相關(guān)博士學(xué)位論文 前10條

1 宋恩海;Yb~(3+)/Mn~(2+)共摻雜鈣鈦礦氟化物ABF_3可調(diào)寬帶上轉(zhuǎn)換發(fā)光研究[D];華南理工大學(xué);2015年

2 鞏思宇;單晶鈦酸鉛納米纖維的稀土摻雜、復(fù)合及其光學(xué)性能研究[D];浙江大學(xué);2016年

3 商曉穎;飛秒光與連續(xù)光激發(fā)的摻Er~(3+)納米材料上轉(zhuǎn)換機(jī)制與操控[D];華東師范大學(xué);2016年

4 崔越;稀土摻雜上轉(zhuǎn)換發(fā)光納米材料NaREF_4制備、優(yōu)化及應(yīng)用的研究[D];北京交通大學(xué);2016年

5 李艾華;飛秒激光激發(fā)稀土摻雜鈮酸鋰單晶的上轉(zhuǎn)換發(fā)光研究[D];哈爾濱工業(yè)大學(xué);2010年

6 祝漢成;高亮度、高熱穩(wěn)定性及抗輻射稀土摻雜鋁酸鹽粉體上轉(zhuǎn)換發(fā)光及其機(jī)理研究[D];東北師范大學(xué);2014年

7 鄭克志;稀土摻雜微納材料中高階多光子上轉(zhuǎn)換發(fā)光及其電子布居過(guò)程的研究[D];吉林大學(xué);2011年

8 董斌;稀土摻雜氧化鋁粉末的上轉(zhuǎn)換發(fā)光特性研究[D];大連理工大學(xué);2007年

9 肖思國(guó);稀土摻雜超微材料的制備與上轉(zhuǎn)換發(fā)光研究[D];湘潭大學(xué);2006年

10 龐濤;稀土摻雜上轉(zhuǎn)換發(fā)光材料制備與發(fā)光性質(zhì)研究[D];大連海事大學(xué);2010年

相關(guān)碩士學(xué)位論文 前10條

1 廖佳燕;光子晶體及金屬銀納米顆粒增強(qiáng)稀土摻雜NaYF_4納米顆粒上轉(zhuǎn)換發(fā)光性質(zhì)研究[D];昆明理工大學(xué);2015年

2 劉雪娥;稀土摻雜氟化物納米晶的合成及發(fā)光性能研究[D];昆明理工大學(xué);2015年

3 趙紅偉;含氧酸鹽基質(zhì)光轉(zhuǎn)換熒光粉的發(fā)光性能研究[D];大連交通大學(xué);2015年

4 翟梓會(huì);試驗(yàn)優(yōu)化設(shè)計(jì)稀土離子摻雜鉬酸鹽熒光粉發(fā)光性質(zhì)的研究[D];大連海事大學(xué);2015年

5 關(guān)瑩;鐿離子Yb~(3+)摻雜釩/鉬酸鹽的合成和發(fā)光性能研究[D];蘇州大學(xué);2015年

6 王欣;稀土上轉(zhuǎn)換發(fā)光納米材料用于近紅外光激發(fā)的光動(dòng)力治療聯(lián)合腫瘤基因治療的研究[D];蘇州大學(xué);2015年

7 陶冶;銷鐿銩摻雜12CaO·7Al_2O_3的制備及上轉(zhuǎn)換發(fā)光性能研究[D];哈爾濱工業(yè)大學(xué);2015年

8 廖艷平;鉺鐿鋰摻雜AZO陶瓷的制備及發(fā)光性能研究[D];哈爾濱工業(yè)大學(xué);2015年

9 潘云星;稀土摻雜Ba_(0.8)Sr_(0.2)TiO_3陶瓷的制備及其上轉(zhuǎn)換發(fā)光性能的研究[D];哈爾濱工業(yè)大學(xué);2015年

10 徐艷玲;稀土離子（Yb~(3+),Tm~(3+),Er~(3+)）共摻雜YAG單晶光纖上轉(zhuǎn)換發(fā)光特性研究[D];浙江大學(xué);2015年

，

本文編號(hào)：1934490