發(fā)布時間：2018-04-27 20:17

  本文選題：普魯士藍(lán) + 納米復(fù)合物�。� 參考：《重慶醫(yī)科大學(xué)》2017年博士論文

【摘要】：第一部分載普魯士藍(lán)靶向納米復(fù)合物的制備及性能檢測目的1.制備一種載普魯士藍(lán)靶向納米復(fù)合物(PLGA-PB-PTX-PEG-FA),并檢測其基本性質(zhì)。2.研究載普魯士藍(lán)靶向納米復(fù)合物體外尋靶能力和聯(lián)合激光對細(xì)胞活性的影響。方法1.以PEG化連接了葉酸(folic acid,FA)的PLGA作為成膜材料,采用雙乳化法,制備裝載普魯士藍(lán)納米粒子(Prussian blue nanoparticles,PB NPs)和紫杉醇(Paclitaxel,PTX)的PLGA-PB-PTX-PEG-FA靶向納米復(fù)合物,并對其粒徑、電位、表面形態(tài)等進(jìn)行檢測;用紫外-可見分光光度法、傅里葉紅外光譜儀、激光共聚焦顯微鏡檢測其紫外吸收光譜、紅外光譜和各組分結(jié)構(gòu)特征;采用0.647 W/cm2,808nm的激光輻照檢測其體外光熱特性;納米復(fù)合物中紫杉醇的包封率及載藥量用高效液相色譜法檢測。2.體外培養(yǎng)乳腺癌細(xì)胞株MDA-MB-231,激光共聚焦評價PLGA-PB-PTX-PEG-FA靶向納米復(fù)合物體外細(xì)胞尋靶能力。采用CCK8法檢測所制備的靶向納米復(fù)合物聯(lián)合激光輻照對細(xì)胞的毒性。結(jié)果1.透射電鏡和掃描電鏡觀察制得的PLGA-PB-PTX-PEG-FA納米復(fù)合物呈球形,形態(tài)規(guī)則,大小尚均勻,分散度好。Malvern激光粒徑儀檢測出PLGA-PB-PTX-PEG-FA納米復(fù)合物粒徑為(236.6±55.04)nm,表面電位為(-24.44±1.7)m V。紫外-可見分光光度計檢測出在PLGA-PB-PTX-PEG-FA納米復(fù)合物和PB NPs吸收波峰位于702nm附近。傅里葉紅外光譜圖結(jié)果顯示,PLGA-PTX-PEG-FA和PB NPs的吸收峰位于1756.23 cm-1 and 2086 cm-1,而PLGA-PB-PTX-PEG-FA納米復(fù)合物同時具有上述兩個特征峰。激光共聚焦顯微鏡顯示,PB NPs激發(fā)后為綠色熒光,PLGA-PTX-PEG-FA為紅色熒光,而PLGA-PB-PTX-PEG-FA納米復(fù)合物為橙黃色熒光。激光輻照下,PLGA-PB-PTX-PEG-FA納米復(fù)合物具有良好的光熱特性和光熱穩(wěn)定性,且隨著PLGA-PB-PTX-PEG-FA納米復(fù)合物濃度增加或激光能量的增加,納米復(fù)合物的光熱轉(zhuǎn)化效能增高。由高效液相色譜法檢測PLGA-PB-PTX-PEG-FA納米復(fù)合物中紫杉醇包封率為77.82%,載藥量為7.22%,具有良好的緩釋特性,在激光輻照下可加快藥物的釋放。2.體外細(xì)胞尋靶實驗顯示,紅色熒光靶向納米復(fù)合物附著于MBA-MD-231乳腺癌細(xì)胞表面,而非靶向組,受體封閉組這兩個組的細(xì)胞周圍幾乎沒有紅色的熒光納米復(fù)合物。CCK8法結(jié)果顯示,PLGA-PB-PTX-PEG-FA聯(lián)合激光輻照組MBA-MD-231的細(xì)胞活性最低,證實其具有體外綜合化療和光熱治療的作用。結(jié)論成功制備出球形、形態(tài)規(guī)則,大小均勻,性質(zhì)穩(wěn)定的PLGA-PB-PTX-PEG-FA靶向納米復(fù)合物。該納米復(fù)合物具有良好的光學(xué)吸收性能和光熱轉(zhuǎn)化特性,載藥量較高,在體外對MBA-MD-231乳腺癌細(xì)胞有良好的靶向能力,聯(lián)合激光輻照,在體外具有良好的聯(lián)合化療和光熱治療腫瘤細(xì)胞的能力。第二部分載普魯士藍(lán)靶向納米復(fù)合物體內(nèi)尋靶,光聲/磁共振多模態(tài)顯像實驗研究目的觀察PLGA-PB-PTX-PEG-FA納米復(fù)合物體外增強磁共振成像(Magnetic resonance imaging,MRI)、光聲成像(Photoacoustic imaging,PAI)成像的能力;于體內(nèi)實驗觀察PLGA-PB-PTX-PEG-FA納米復(fù)合物對裸鼠MDA-MB-231移植瘤的靶向效果,及PA/MRI多模態(tài)成像效果,了解PLGA-PB-PTX-PEG-FA納米復(fù)合物增強PA/MRI的能力及原理。方法1.選取10只MDA-MB-231移植瘤裸鼠進(jìn)行小動物活體熒光成像,隨機分為兩組:靶向納米復(fù)合物(DIR/PLGA-PB-PTX-PEG-FA)組和非靶向納米復(fù)合物(Di R/PLGA-PB-PTX-PEG)組,每只裸鼠經(jīng)尾靜脈緩慢注射0.2m L(20mg/m L)納米復(fù)合物。注射成功后分別于1h、2h、4h、6h及24h利用小動物活體熒光成像系統(tǒng)采集圖像。對比觀察兩組腫瘤局部的熒光強度,圖像的定量分析利用Living Image軟件系統(tǒng)測得。待24h成像完畢后,處死裸鼠,解剖腫瘤、心、肝、脾、肺、腎、腦,行離體熒光成像,并計算各部位離體熒光強度。2.配置不同濃度的PLGA-PB-PTX-PEG-FA納米復(fù)合物和PLGA-PTX-PEG-FA,對照組為雙蒸水,使用Vevo?LAZR光聲成像系統(tǒng)和3.0T磁共振掃描儀分別采集光聲圖像和T1*WI圖像。應(yīng)用光聲系統(tǒng)自帶軟件測量各樣品的光聲值。應(yīng)用系統(tǒng)軟件測定各樣本信號強度,計算各樣品的信號增強百分比。建立裸鼠MDA-MB-231移植瘤模型,選擇15只隨機分為三組,經(jīng)尾靜脈分別緩慢注射靶向納米復(fù)合物(PLGA-PB-PTX-PEG-FA)、非靶向納米復(fù)合物(PLGA-PB-PTX-PEG)及生理鹽水。注射前及注射后1h、2h、4h、6h及24h利用光聲成像儀采集圖像。利用儀器自帶軟件對注射試劑前后的腫瘤感興趣區(qū)的圖像進(jìn)行光聲信號定量分析,計算各樣品的光聲信號比率。同樣的分組方法,利用Philips 3.0T超導(dǎo)型磁共振儀和小動物線圈采集腫瘤在不同時間的T1WI圖像,測量各時間點增強前后同一層面裸鼠腫瘤及大腿肌肉感興趣區(qū)的信號強度值(Signal intensity,SI)SItumor及SImuscle,計算相對信號強度(Relative signal intensity,SIr)及信號強度增強率(Percentage of signal intensity enhancement,PSIE)結(jié)果1.結(jié)果顯示注射前兩組均未見熒光顯示,在尾靜脈注射靶向納米復(fù)合物后,靶向組腫瘤內(nèi)部、脾、腦、脊柱可見Di R標(biāo)記的靶向納米復(fù)合物聚集發(fā)出的紅色熒光,在注射后1h熒光最強。隨時間延長,腫瘤、脊柱、腦部的熒光強度逐漸減低,而肝區(qū)的熒光強度逐漸加強。在注射后24h,腫瘤區(qū)域、脾和肝區(qū)仍可見少量熒光顯示。而尾靜脈注射非靶向納米復(fù)合物后,非靶向組腫瘤內(nèi)部沒有熒光顯示,而肝區(qū)見熒光顯示,24h后消失。離體活體熒光可見兩組的肝、脾、肺均有熒光顯示,但只有靶向組的腫瘤有熒光顯示,非靶向組的腫瘤沒有熒光聚集。Living Image軟件系統(tǒng)分析靶向組在體和離體腫瘤及離體脾組織區(qū)域熒光強度均明顯高于非靶向組,P0.05,差異具有統(tǒng)計學(xué)意義。2.體外光聲顯影結(jié)果和體外MRI結(jié)果顯示,與不含PB NPs的納米粒(PLGA-PTX-PEG-FA)及雙蒸水相比,PLGA-PB-PTX-PEG-FA納米復(fù)合物可明顯增強光聲顯像和MRI T1顯像,且隨著PLGA-PB-PTX-PEG-FA納米復(fù)合物濃度的增加,光聲顯像和MRI顯像增強,光聲值和MRI信號增強百分比(PSIE)也逐漸增強,與PLGA-PTX-PEG-FA組和雙蒸水組相比,P0.05,差異有統(tǒng)計學(xué)意義。體內(nèi)部分,靶向組在注射靶向納米復(fù)合物后,腫瘤區(qū)域光聲信號和MRI信號在1h最明顯,然后逐漸下降,但在注射后24h依然還有明顯光聲信號和MRI信號。而非靶向組和生理鹽水組未見明顯光聲和MRI增強顯影。靶向組光聲信號比率和信號強度增強率與其他兩組比較,P0.05,差異有統(tǒng)計學(xué)意義。結(jié)論制備的PLGA-PB-PTX-PEG-FA靶向納米復(fù)合物,具有良好的體內(nèi)靶向能力,可以特異性靶向至腫瘤區(qū)域。其具有體外光聲和磁共振顯影的性能,并且可增強乳腺癌移植瘤的光聲及磁共振顯像,是一種有效的多模態(tài)成像靶向納米復(fù)合物。第三部分載普魯士藍(lán)靶向納米復(fù)合物綜合治療裸鼠乳腺癌的研究目的研究PLGA-PB-PTX-PEG-FA靶向納米復(fù)合物聯(lián)合激光促進(jìn)藥物釋放對裸鼠MDA-MB-231移植瘤的綜合治療效果。方法選取35只MDA-MB-231移植瘤裸鼠,隨機分為7組:PBS對照組(control)、單純紫杉醇藥物組(PTX)、不含藥物納米粒組(PLGA-PB-PEG-FA)、靶向納米復(fù)合物組(PLGA-PB-PTX-PEG-FA)、不含藥物納米粒+激光輻照組(PLGA-PB-PEG-FA+NIR)、靶向納米復(fù)合物+激光輻照組(PLGA-PB-PTX-PEG-FA+NIR)和單純激光輻照組(NIR)。各組給予尾靜脈注射相對應(yīng)試劑,其中PLGA-PB-PEG-FA+NIR和PLGA-PB-PTX-PEG-FA+NIR組在注射試劑后1h左右,用808nm輸出功率0.647 W/cm2的激光輻照腫瘤區(qū)域10min。激光輻照組則僅用上述參數(shù)激光輻照腫瘤區(qū)域10min。用紅外成像儀檢測上述處理導(dǎo)致的溫度變化,每10s記錄一次溫度。定期測量腫瘤體積大小,計算相對腫瘤體積(The relative tumor volumes,RTV)。于治療后21d處死裸鼠,剝?nèi)∧[瘤組織并稱取質(zhì)量,計算腫瘤抑瘤率(Tumor inhibition rate,TIR)。腫瘤細(xì)胞的增殖和凋亡分別用免疫組化PCNA法和TUNEL法檢測,計算腫瘤細(xì)胞增殖指數(shù)(Proliferation index,PI)和凋亡指數(shù)(Apoptotic index,AI)。HE染色查看各組裸鼠腫瘤壞死情況及PLGA-PB-PTX-PEG-FA+NIR組和對照組裸鼠的心、肝、脾、肺、腎病理切片情況。結(jié)果尾靜脈注射PLGA-PB-PTX-PEG-FA靶向納米復(fù)合物后1h,激光輻照腫瘤區(qū)域后,腫瘤表面的溫度迅速上升,上升至52±3.05℃。PLGA-PB-PTX-PEG-FA+NIR組荷瘤裸鼠的腫瘤在處理后3天結(jié)痂,處理后12天明顯縮小,到處理后第21天,未見明顯增長,腫瘤體積與其他各組相比縮小最明顯,相對腫瘤生長曲線呈逐漸下降的趨勢。其他各組腫瘤均有不同程度的增長。除了NIR組,PLGA-PB-PEG-FA組和對照組,其他各處理組相對腫瘤體積兩兩比較P0.05,差異具有統(tǒng)計學(xué)意義。PLGA-PB-PTX-PEG-FA+NIR組表現(xiàn)出明顯的抑瘤效果,質(zhì)量抑瘤率為98.86%,其他各組抑瘤率依次下降。PCNA和TUNEL結(jié)果顯示PLGA-PB-PTX-PEG-FA+NIR組PI指數(shù)最低,AI指數(shù)最高。除了NIR組,PLGA-PB-PEG-FA組和對照組,其他各處理組PI指數(shù)及AI指數(shù)分別兩兩比較P0.05,差異具有統(tǒng)計學(xué)意義。腫瘤組織HE染色,PLGA-PB-PTX-PEG-FA+NIR組可見大量壞死,鏡下呈紅色片狀無結(jié)構(gòu)區(qū)域。PLGA-PB-PTX-PEG-FA+NIR組的心、肝、脾、肺、腎和對照組對比,HE染色未見明顯異常。結(jié)論制備的PLGA-PB-PTX-PEG-FA靶向納米復(fù)合物能夠靶向至腫瘤區(qū)域,結(jié)合光熱和化療作用,增加腫瘤綜合治療效果。其有能力成為光聲、磁共振多模態(tài)顯影劑及影像介導(dǎo)下結(jié)合化療和光熱綜合腫瘤治療的靶向納米物質(zhì)。
[Abstract]:The first part of the preparation and performance detection of Prussian blue targeted nanocomposites 1. preparation of a Prussian blue targeting nanocomposite (PLGA-PB-PTX-PEG-FA), and detection of its basic properties.2. study the target ability of Prussian blue target to nano composite objects and the effect of combined light excitation on cell activity. Method 1. PEG connection The PLGA of folic acid (FA) was used as a film forming material, and a double emulsification method was used to prepare the PLGA-PB-PTX-PEG-FA target of Prussian blue nanoparticles (Prussian blue nanoparticles, PB NPs) and paclitaxel (Paclitaxel, PTX), and the particle size, potential and surface morphology were detected, and UV visible spectrophotometry was used. The UV absorption spectrum, infrared spectrum and the structure of each component were detected by laser confocal microscopy, and the photothermal characteristics in vitro were detected by 0.647 W/cm2808nm laser irradiation. The encapsulation efficiency and drug loading of paclitaxel in nanocomposites were detected by high performance liquid chromatography with.2. in vitro culture of breast cancer cell line MDA-MB-2 31, the target ability of the PLGA-PB-PTX-PEG-FA target to the outer cells of nanocomposite objects was evaluated by laser confocal microscopy. The toxicity of the target nanocomposite combined with laser irradiation on the cells was detected by CCK8. Results the PLGA-PB-PTX-PEG-FA nanocomposites obtained by 1. transmission electron microscopy and scanning electron microscopy were spherical, shape rule, size Shang Junyun, The particle size of PLGA-PB-PTX-PEG-FA nano composite was detected by a good dispersion.Malvern laser particle size analyzer (236.6 + 55.04), and the surface potential was (-24.44 + 1.7) m V. UV VIS spectrophotometer. The PLGA-PB-PTX-PEG-FA nanocomposite and PB NPs absorption wave peak were located near the 702nm. The Fourier infrared spectrogram results showed that PLGA-PTX-PEG-FA The absorption peaks of PB NPs and PB NPs are located at 1756.23 cm-1 and 2086 cm-1, while PLGA-PB-PTX-PEG-FA nanocomposites have the above two characteristic peaks. The laser confocal microscope shows that PB NPs is excited by green fluorescence, PLGA-PTX-PEG-FA is red fluorescence, and PLGA-PB-PTX-PEG-FA nanocomplex is orange yellow fluorescence. Under laser irradiation, PLGA-PB-PTX -PEG-FA nanocomposites have good photothermal properties and photothermal stability. The photothermal conversion efficiency of nanocomposites increases with the increase of the concentration of PLGA-PB-PTX-PEG-FA nanocomposites or the increase of laser energy. The encapsulation efficiency of paclitaxel in PLGA-PB-PTX-PEG-FA nanocomposites is 77.82% and the drug loading is 7.2 by HPLC. 2%, with good release characteristics, the release of.2. in vitro could be accelerated by laser irradiation. The target experiment showed that the red fluorescent target was attached to the surface of MBA-MD-231 breast cancer cells, but not in the target group, and the two groups in the receptor closed group had almost no red fluorescent nanocomposite.CCK8 method. The PLGA-PB-PTX-PEG-FA combined laser irradiated group MBA-MD-231 has the lowest cell activity, which proves that it has the effect of comprehensive chemotherapy and photothermal treatment in vitro. Conclusion the spherical, regular, uniform and stable PLGA-PB-PTX-PEG-FA targeted nanocomposites have been successfully prepared. The nanocomposites have good optical absorption properties and light. Heat conversion characteristics, high drug loading, good targeting ability for MBA-MD-231 breast cancer cells in vitro, combined laser irradiation, with good combination of chemotherapy and photothermal treatment of tumor cells in vitro. Second part of Prussian blue targeted nanocomposite objects in the target, photoacoustic / MRI multi-modal imaging experimental research purposes Observe the ability of PLGA-PB-PTX-PEG-FA nanocomposite objects to enhance magnetic resonance imaging (Magnetic resonance imaging, MRI), photoacoustic imaging (Photoacoustic imaging, PAI) imaging, and to observe the target effect of PLGA-PB-PTX-PEG-FA nanocomposites on MDA-MB-231 transplanted tumor in nude mice in vivo, and the effect of PA/MRI multimodal imaging, and to understand PLGA-PB-PTX-P The ability and principle of EG-FA nanocomposites enhanced PA/MRI. Methods 1. selected 10 MDA-MB-231 xenografts in nude mice in vivo fluorescence imaging, randomly divided into two groups: target nanocomposite (DIR/PLGA-PB-PTX-PEG-FA) group and non target nanocomposite (Di R/PLGA-PB-PTX-PEG) group, each nude mice were injected slowly via the tail vein of 0.2m L (20mg/m) L) nanocomposites. After the injection, the images were collected from 1H, 2h, 4h, 6h and 24h using the living fluorescent imaging system of small animals. The fluorescence intensity of the two groups was observed. The quantitative analysis of the images was measured by the Living Image software system. After the 24h imaging was completed, the tumor, the heart, the liver, the spleen, the kidney, the brain, and the brain were dissected. Optical imaging was used to calculate the fluorescence intensity of different parts of each part of.2. with different concentrations of PLGA-PB-PTX-PEG-FA nanocomposites and PLGA-PTX-PEG-FA. The control group was double water. The Vevo? LAZR photoacoustic imaging system and the 3.0T magnetic resonance scanner were used to collect the photoacoustic images and T1*WI images respectively. The photoacoustic values of the samples were measured by the photoacoustic system self band software. The signal intensity of each sample was measured by system software, and the percentage of signal enhancement in each sample was calculated. A model of MDA-MB-231 transplanted tumor in nude mice was established. 15 rats were randomly divided into three groups, and the target nano complex (PLGA-PB-PTX-PEG-FA), non target nanocomposite (PLGA-PB-PTX-PEG) and physiological saline were injected through the tail vein respectively. 1H, 2h, 4h, 6h and 24h are used to collect images using a photoacoustic imaging instrument. The instrument is used to carry out a quantitative analysis of the photoacoustic signal of the tumor in the region of interest before and after the injection of the injection reagent and calculate the ratio of the photoacoustic signal to each sample. The same grouping method uses the Philips 3.0T superconductance MRI and the small animal coils to collect tumors in no T1WI images at the same time were used to measure the signal intensity (Signal intensity, SI) SItumor and SImuscle at the same level of nude mice and thigh muscles before and after each time point enhancement, and the relative signal intensity (Relative signal intensity, SIr) and the enhancement of signal intensity were calculated (Percentage of) results 1. The results showed that there was no fluorescence in the two groups before the injection. After the injection of the target nano complex in the tail vein, the target group of the tumor, the spleen, the brain and the spinal column showed the red fluorescence of the Di R labeled nanocomposite aggregation. The fluorescence intensity of the 1H was strongest after the injection. The fluorescence intensity of the tumor, spinal column and brain gradually decreased with time, and the liver region was gradually reduced. The fluorescence intensity was gradually strengthened. After injection of 24h, the tumor area, the spleen and the liver still showed a small amount of fluorescence. After the injection of the non targeting nanocomposite, the non targeting group had no fluorescent display in the non targeting group, while the liver region showed fluorescence display, and then disappeared after 24h. The fluorescence of two groups of liver, spleen and lung were shown in the isolated living body, but only the target was targeted. The tumor of the group had fluorescent display, the tumor of the non target group had no fluorescence aggregation.Living Image software system analysis, the fluorescence intensity of the target group in the target group and the isolated tumor and the isolated spleen tissue were significantly higher than that of the non targeting group, P0.05, the difference was statistically significant in.2. in vitro photoacoustic development and in vitro MRI results, with the non PB NPs content. Compared with the rice grain (PLGA-PTX-PEG-FA) and double water, the PLGA-PB-PTX-PEG-FA nanocomposites can obviously enhance the photoacoustic imaging and MRI T1 imaging, and with the increase of the PLGA-PB-PTX-PEG-FA nanocomposite concentration, the photoacoustic imaging and MRI imaging are enhanced, and the percentage of the photoacoustic and MRI signal enhancement (PSIE) is also enhanced gradually, with the PLGA-PTX-PEG-FA group and the double steam water. Compared with the group P0.05, the difference was statistically significant. In the body part, the target group was most obvious in the tumor area after injection of the targeted nanocomplex, and the tumor region photoacoustic signal and MRI signal were most obvious in 1H, and then decreased gradually, but there was still obvious photoacoustic signal and MRI signal after the injection, but no obvious photoacoustic and MRI enhanced development was not found in the target group and the normal saline group. Compared with the other two groups, the ratio of the photoacoustic signal to the target group and the enhancement rate of the signal intensity were compared with the other two groups. The difference was statistically significant. Conclusion the prepared PLGA-PB-PTX-PEG-FA targeted nanocomposite has good target ability in vivo and can specifically target to the tumor area. It has the performance of photoacoustic and magnetic resonance imaging in vitro, and can enhance milk. Photoacoustic and magnetic resonance imaging of adenocarcinoma xenograft is an effective multi-modal imaging target nanocomposite. The study of the third part of Prussian blue targeting nanocomposite in the treatment of breast cancer in nude mice: a study of PLGA-PB-PTX-PEG-FA targeted nanocomposite combined with laser induced drug release for nude mice MDA-MB-231 xenografts Methods 35 MDA-MB-231 transplanted nude mice were randomly divided into 7 groups: PBS control group (control), simple paclitaxel group (PTX), no drug nanoparticles group (PLGA-PB-PEG-FA), targeted nanocomposite group (PLGA-PB-PTX-PEG-FA), no drug nanoparticles + laser irradiation group (PLGA-PB-PEG-FA+NIR), and target nanocomposite + excitation Light irradiation group (PLGA-PB-PTX-PEG-FA+NIR) and laser irradiation group (NIR). Each group was given a relative test agent in the tail vein, of which the PLGA-PB-PEG-FA+NIR and PLGA-PB-PTX-PEG-FA+NIR groups were about 1h after the injection of the reagent, and the laser irradiation group of the tumor area 10min. laser irradiated by the laser output power of 0.647 W/cm2 was only used for the above parameters. The tumor area 10min. was used to detect the temperature changes caused by the above treatment by infrared imager. The tumor volume was measured at a time of 10s. The volume of tumor was measured regularly and the relative tumor volume (The relative tumor volumes, RTV) was calculated. After the treatment, 21d was killed in nude mice, the tumor tissue was stripped and the mass was called, and the tumor suppressor rate (rate, T) was calculated. T (Tumor inhibition rate, T) IR). The proliferation and apoptosis of tumor cells were detected by immunohistochemistry PCNA method and TUNEL method respectively. The tumor cell proliferation index (Proliferation index, PI) and apoptosis index (Apoptotic index, AI).HE were calculated to examine the tumor necrosis in nude mice and the heart, liver, spleen, lung and kidney pathology of the mice in the PLGA-PB-PTX-PEG-FA+NIR group and the control group. Results after the PLGA-PB-PTX-PEG-FA targeted nanocomposite was injected into the tail vein 1H, the tumor surface temperature increased rapidly after laser irradiation, and increased to 52 + 3.05 C.PLGA-PB-PTX-PEG-FA+NIR group of tumor bearing nude mice after 3 days after treatment. After treatment, the tumor was markedly reduced, and no significant growth was found on the twenty-first day after treatment. Tumor body had not been increased. The volume of the product decreased most obviously compared with the other groups, and the relative tumor growth curve decreased gradually. Other groups had different degrees of growth. In the group of NIR, group PLGA-PB-PEG-FA and control, the other groups were compared with 22 of the tumor volume, P0.05, and the difference had the significance of the group.PLGA-PB-PTX-PEG-FA+NIR group. The tumor suppressor effect was 98.86%, and the tumor inhibition rate in other groups decreased by.PCNA and TUNEL. The PI index in PLGA-PB-PTX-PEG-FA+NIR group was the lowest, and the AI index was the highest. The PI index and AI index of other treatment groups were 22 compared with the NIR group and the control group, and the difference was statistically significant. HE staining, group PLGA-PB-PTX-PEG-FA+NIR showed a large number of necrosis, under the microscope, the heart, liver, spleen, lung, kidney and the control group were compared with the red flaky unstructured area.PLGA-PB-PTX-PEG-FA+NIR group, and the HE staining was not obvious. Conclusion the prepared PLGA-PB-PTX-PEG-FA targeted nanocomposites can be targeted to the tumor area, combined with the effect of photothermal and chemotherapy. Combined with tumor combined therapy, it has the ability to become a target nanomaterial with photoacoustic, magnetic resonance multimodal developer and imaging mediate combined with chemotherapy and photothermal integrated tumor therapy.

【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R737.9

【相似文獻(xiàn)】

相關(guān)期刊論文 前7條

1 王偉;王玉;鄭楓;徐蘇穎;丁楊;周建平;;尿刊酸修飾殼聚糖載基因納米復(fù)合物的制備及體外性質(zhì)[J];中國藥科大學(xué)學(xué)報;2011年06期

2 王曉宇;孫李平;朱全剛;張瑋;張敏;張麗娟;戴子淵;高申;;透明質(zhì)酸/聚酰胺-胺三元納米基因復(fù)合物的構(gòu)建及其體外評價[J];第二軍醫(yī)大學(xué)學(xué)報;2012年12期

3 王[?鈞;操鋒;平其能;;雙氯芬酸鈉層狀雙金屬氫氧化物納米復(fù)合物的制備及性質(zhì)研究[J];中國藥科大學(xué)學(xué)報;2009年04期

4 胥洪鵑;張陽德;陳玉祥;汪啟爐;;CTAB@SiO_2納米復(fù)合物作為基因轉(zhuǎn)染載體的研究[J];中國現(xiàn)代醫(yī)學(xué)雜志;2013年06期

5 孫曉利;宋繼斌;劉東華;李鵬;魯在君;張娜;;PEG-b-PLL的合成及其自組裝納米基因載體的研究[J];中國生化藥物雜志;2010年05期

6 白祖海;張瑾;吾爾葉提;;基于Cu~(2+)和碳納米管納米復(fù)合物的過氧化氫生物傳感器測定過氧化氫[J];中國衛(wèi)生檢驗雜志;2014年18期

7 耿海霞;郭秀娟;錢君榮;封偉;;羥基磷灰石/凝膠納米復(fù)合物修復(fù)兔顱骨缺損的影像學(xué)評估[J];中國組織工程研究;2014年34期

相關(guān)會議論文 前10條

1 祁寧;王元為;王丹丹;陳志權(quán);;Co_3O_4/ZnO納米復(fù)合物微結(jié)構(gòu)的正電子湮沒研究[A];第十四屆全國核物理大會暨第十屆會員代表大會論文集[C];2010年

2 吳麗艷;郭志華;滕利榮;高波;;羥基磷灰石/藥物納米復(fù)合物的制備研究[A];吉林省第六屆生命科學(xué)大型學(xué)術(shù)報告會論文集[C];2008年

3 陳譜;曹菲菲;張俐娜;;大豆蛋白／氫氧化鋁納米復(fù)合物的結(jié)構(gòu)與性能[A];2005年全國高分子學(xué)術(shù)論文報告會論文摘要集[C];2005年

4 王曉亮;顧強;孫平川;H H Winter;薛奇;;固體核磁共振雙量子氫譜對聚丁二烯/粘土納米復(fù)合物中鏈動力學(xué)的研究[A];2011年全國高分子學(xué)術(shù)論文報告會論文摘要集[C];2011年

5 鄭田;盧曉峰;邊秀杰;張城城;王策;;CNT/PPy/K_xMnO_2三元納米復(fù)合物的制備及電催化性能研究[A];中國化學(xué)會第28屆學(xué)術(shù)年會第4分會場摘要集[C];2012年

6 武海青;何光裕;陳海群;孫小強;汪信;;多價態(tài)銀-還原氧化石墨烯納米復(fù)合物的光合成及其抗菌應(yīng)用[A];中國化學(xué)會第28屆學(xué)術(shù)年會第5分會場摘要集[C];2012年

7 葉春雪;楊榮杰;儀德啟;;聚磷酸銨/鈣基蒙脫土納米復(fù)合物的結(jié)構(gòu)與性質(zhì)[A];2012年中國阻燃學(xué)術(shù)年會論文集[C];2012年

8 周輝輝;李娟;劉又年;;自組裝法制備茶多酚-明膠-葡聚糖納米復(fù)合物[A];2011年全國高分子學(xué)術(shù)論文報告會論文摘要集[C];2011年

9 李輝;吳思多;吳錦榮;黃光速;;石墨烯/聚苯乙烯納米復(fù)合物的導(dǎo)電性研究[A];2011年全國高分子學(xué)術(shù)論文報告會論文摘要集[C];2011年

10 仇士龍;袁鉆如;潘磊;王玉婷;謝鴻峰;程昒時;;氧化石墨/環(huán)氧樹脂納米復(fù)合物的固化行為研究[A];中國化學(xué)會第十五屆全國化學(xué)熱力學(xué)和熱分析學(xué)術(shù)會議論文摘要[C];2010年

相關(guān)博士學(xué)位論文 前10條

1 陳真真;智能響應(yīng)性納米載體的基因輸送與腫瘤治療的研究[D];蘭州大學(xué);2015年

2 劉莉;含c(RGDfk)環(huán)肽的自組裝納米復(fù)合物RPM/siRNA在腫瘤靶向治療中的應(yīng)用[D];南方醫(yī)科大學(xué);2015年

3 羅慶平;Al/Fe_2O_3-RDX納米復(fù)合物的反應(yīng)特性研究[D];北京理工大學(xué);2015年

4 陳美玲;石墨烯納米復(fù)合物的制備及其在生物成像中的應(yīng)用研究[D];東北大學(xué);2013年

5 劉媛媛;基于普魯蘭多糖的納米藥物遞送系統(tǒng)靶向抗肝癌作用研究[D];天津醫(yī)科大學(xué);2015年

6 楊欣;石墨烯基納米復(fù)合物制備、表征及其電化學(xué)傳感性能研究[D];湖南大學(xué);2016年

7 王鑫巖;貴金屬/二氧化鈦納米復(fù)合物的光電性質(zhì)及光催化性能研究[D];吉林大學(xué);2017年

8 尚婷婷;載普魯士藍(lán)靶向納米復(fù)合物多模態(tài)顯像及綜合治療裸鼠乳腺癌的實驗研究[D];重慶醫(yī)科大學(xué);2017年

9 李雪;含咪唑陽離子功能化聚合物及其納米復(fù)合物的制備與性能研究[D];浙江大學(xué);2012年

10 劉偉祿;新型納米復(fù)合物的制備及在電化學(xué)分析中的應(yīng)用[D];吉林大學(xué);2013年

相關(guān)碩士學(xué)位論文 前10條

1 李嘉琳;功能化石墨烯納米復(fù)合物及其生物小分子電化學(xué)實時傳感研究[D];西南大學(xué);2015年

2 黎青勇;纖維素基納米稀土發(fā)光復(fù)合材料的制備及發(fā)光性能研究[D];華南理工大學(xué);2015年

3 余波杰;可共載化療藥物和基因以協(xié)同增強其抗腫瘤功效的葉酸修飾兩親性殼聚糖納米載體[D];復(fù)旦大學(xué);2014年

4 季衛(wèi)東;近紅外光響應(yīng)的納米復(fù)合物的制備及其藥物控釋性能研究[D];蘇州大學(xué);2015年

5 盛仲夷;有機化改性蒙脫土的制備及其在聚合物中的應(yīng)用[D];浙江大學(xué);2013年

6 柳素青;合成MTX/LDHs納米復(fù)合物的研究及其抗腫瘤效應(yīng)的探索[D];南京師范大學(xué);2015年

7 霍曉磊;MTX納米復(fù)合物的可控合成、組裝及其對腫瘤細(xì)胞的抑制作用研究[D];南京師范大學(xué);2015年

8 葉亞;碳載錫及其合金納米復(fù)合物的制備及儲鋰性能研究[D];南京師范大學(xué);2015年

9 王日明;鐵基氧化物降解DDT性能的研究[D];山東大學(xué);2015年

10 黃磊;氧化石墨烯基磁性熒光多功能復(fù)合納米材料的研究[D];重慶理工大學(xué);2015年

，

本文編號：1812161