用于血管介入栓塞治疗的新型栓塞剂温敏纳米凝胶的实验研究
|
摘要
第一部分温敏纳米凝胶相关特性研究
目的研究新型栓塞剂温敏型聚(N—异丙基丙烯酰胺—co—甲基丙烯酸丁酯)纳米凝胶(简称温敏纳米凝胶)的相关特性及其作为血管栓塞剂的有效性、安全性。
材料与方法对温敏纳米凝胶进行一系列有关特性的鉴定，并分别进行体外模拟实验及10只家兔肝动脉栓塞实验，另10只用生理盐水注入肝动脉作对照。结果温敏纳米凝胶为温度敏感性栓塞材料，常温下流动性好，呈液体状态，37℃时完全凝固，失去流动性，且具有高触变性，易经导管注射；具有良好的血液相容性和组织相容性，无致热原性及毒性作用；栓塞部位主要是末梢小动脉；经光镜观察其对正常肝组织损伤轻微，仅出现栓塞部位的肝细胞变性和坏死。
结论温敏纳米凝胶使用方便、安全，是一种较理想的末梢型血管栓塞剂。可用于进一步动物实验。
第二部分温敏纳米凝胶栓塞正常家兔肾动脉的栓塞实验研究
目的应用温敏纳米凝胶栓塞家兔的肾动脉及肝动脉，探讨温敏纳米凝胶作为血管栓塞剂的可行性。
材料与方法60只新西兰大白兔，分别用温敏纳米凝胶栓塞右肾动脉及肝动脉，并用PVA栓塞右肾动脉作对照，术后观查家兔一般情况、存活时间、肝功能及病理改变。
结果温敏纳米凝胶为温度敏感性栓塞材料，易经介入导管注射，栓塞后家兔精神、饮食正常，肾功能14天可恢复正常；凝胶可根据需要栓塞各级动脉，栓塞末梢血管牢固，时间达两月以上；栓塞后家兔无明显毒副反应；病理检查右肾动脉栓塞后3天即出现梗死，肝组织14天后出现坏死；35天后被凝胶栓塞的肝组织及肾组织均出现弥漫性坏死。
结论温敏纳米凝胶使用方便、安全，栓塞血管效果好，是一种较理想的血管栓塞剂。
第三部分温敏纳米凝胶对兔VX2移植性肝癌栓塞效果的实验研究
实验一用于介入栓塞剂研究的肝癌模型的建立
目的建立兔VX2移植性肝癌模型、探讨其影像学及病理学特点。
材料与方法将50只新西兰大白兔采用移植法建立兔VX2移植性肝癌模型，于移植术后13天行DSA、MRI、CT及病理检查。
结果有48只兔接种成功，其影像学及病理学表现均类似于人类原发性肝癌。
结论兔VX2移植性肝癌模型可用于血管栓塞剂温敏纳米凝胶的实验研究。
实验二温敏纳米凝胶介入栓塞治疗兔VX2移植性肝癌的疗效
目的评价温敏纳米凝胶介入栓塞治疗兔VX2移植性肝癌的疗效。
材料和方法将45只新西兰大白兔采用移植法建立移植性肝癌模型，于移植术后13天后行MRI检查，测量肿瘤体积(V1)，再随机分成3组，A组：经肝动脉注入温敏纳米凝胶0.6ml；B组：经肝动脉灌注超液态碘油0.6ml+0.25mg明胶海绵粉；C组：经肝动脉灌注生理盐水1ml。14天后再行磁共振检查以确定肿瘤体积(V2)，对三组间肿瘤生长率(V2／V1)进行比较。先进行大体标本观察，包括肿瘤大小、坏死、出血情况。镜下组织学观察肿瘤细胞排列方式、坏死及肝内转移等。
结果A、B、C三组间肿瘤生长速率不完全相同，肿瘤大小术前分别为0.068±0.11cm~3，0.071±0.23 cm~3，0.069±0.19 cm~3；术后14天分别为0.289±0.18cm~3，1.018±0.21cm~3，4.290±0.67cm~3，术后三组间肿瘤体积有显著性差异(p＜0.01)，两两比较各组间均有显著性差异(p＜0.01)；各组间肝表面转移灶及显微镜下瘤周1cm肝组织转移灶不完全相同，两两比较示A组与B组、A组与C组均存在显著性差异(p＜0.01)，而B、C两组无统计学差异(p＞0.05)。
结论温敏纳米凝胶的栓塞治疗对兔VX2移植性肝癌具有显著的生长抑制作用，是一种较理想的肝癌栓塞物质
Part oneStudy on the Characteristics of Thermosensitve Poly Nanogel
Objective To study the correlation properties of thermosensitve poly (N-isopropylacrylamide- co-butyl methacrylate) nanogel and the efficacy, safety andcorrelative characteristics as a vascular embolization agent.
Materials and methods Related characteristics of thermosensitve poly nanogel werestudied. Extra corporeal simulation experiments and hepatic arterial embolization of 10rabbits were performed with thermosensitve poly nanogel respectively, others 10 rabbitsembolized with Normal saline as a control.
Results Thermosensitve poly nanogel is a thermosensitive embolic material in liquid statewith fine fluidity at room temperatrue, fully solidifies at 37℃and loses fluidity, having ahigh thixotropy and being easily injected through all sorts of interventional catheters andthe embolization agent has hemo-compatibility and good histocompat- ibility, withoutpyrogenetic response and toxicity. Thermosensitve poly nanogel mainly embolized theperipheral arteries. Slight injuries of normal hepatic tissues with hepatic cytonecrosisandendochyloma focal necrosis were found through electronic microscopy.
Conclusion Thermosensitve poly nanogel is a safe and effective peripheral embolizationagent in experimental application and a and may be confirmed in further animalexperiments.
Part twoThe Animal experimental study On the Vascular Embolization Agent ofThermosensitve Poly Nanogel
objective To emblazc the right renal artery and the hepatic arterial of rabbits withthermosensitve poly nanogel and investigate its feasibility as a vascular embolization agent.
Materials and methods To emblize the right renal artery the hepatic arterial of 60 rabbitswith thermosensitvc poly nanogel, PVA as a control. General condition, survival time,hepatic and renal function and pathological changes of the rabbits treated byThermosensitve poly nanogel were performed. Follow-up angiography was performed forembolic efficacy.
Results Thermosensitve poly nanogel which easily injected through all sorts ofinterventional catheters is a thermosensitive embolic material. The spirit, drink, eating,hepatic function were normal after embolization and renal function could get normal after14 days. Thermosensitve poly nanogel could emblize arteries at all levels according toexperimental need and could emblaze the periphcral arteries firmly with maintainingocclusion for over one month without pyrogenetic response and toxicity. Pathologically,infarction of renal tissuc was found 3 days after the right renal were embolized,whilehepatic tissue necrosis was found 14days after the hepatic were embolized and diffusenecrosis of renal and hepatic tissue was found 35 days after operation.
Conclusion Thermosensitve poly nanogel is a safe and convincnt embolization agentwith good angiocmbolic function and is an ideal vascular embolization agent.
Part threeTreatment effect of Thermosensitve Poly Nanogel for Rabbit VX2transplanted hepatocarcinoma model
Test 1 Establishing Rrabbit transplanted VX2 hepatocarcinoma modelfor study of Vascular embolization agent
Objective To establish the rabbit VX2 hepatocarcinoma model and study the features ofimaging and pathology examination.
Materials and methods Fifty Newzealand rabbits hepatocarcinoma model wereestablished by VX2 tumor implantation, Digital subtraction angiography(DSA), magneticresonance imaging(MRI), computed tomography(CT) scanning and Pathology wereperformed 13 days after implantation.
Result Succecssful implantation was obtained in 38 rabbits by the examination ofMRI.The imagology and pathology are all similar with human hepatocarcinoma.
Conclusion Rabbit VX2 heptocarcinoma model is suitable for interventional experimentstudy of the vascular embolization agent of thermosensitve poly nanogel onhepatocarcinoma.
Test 2 Treatment effect of Thermosensitve Poly Nanogel for Rabbit VX2transplanted hepatocarcinoma model
objective To observe the inhibiting effect of thermosensitve poly nanogel on rabbit VX2transplanted hepatocarcinoma model through emblazing hepatic artery.
Materials and methods 45 rabbits hepatoma model were established by VX2 tumorimplantation.The tumor volume (V1) was measured by magnetic resonance imaging 13days after implantation, then the rabbits were splited randomly into three group(n=15).Andafter 14 days thermosensitve poly nanogel 0.6ml,ultrofluid lipiodol 0.6ml and 0.25mggelfoam spong, Normal saline 1 ml were infused though hepatic artery respectively. Afteranother 14days MRI were performed once again to determine the tumor volume and Thetumor growth rates of three groups were compared. Gross specimen were performedfirstly, including tumor size, necrosis, hemorrhage and liver surface metastases and thearrangement of tumor cells, necrosis and intrahepatic metastasis were observed throughhistological observation under a microscope.
Results Average tumor volume of the three groups before operation were0.068±0.11cm~3, 0.071±0.23 cm~3, 0.069±0.19 cm~3, while after operation, average tumorvolume of the three group were 0.289±0.18cm~3, 1.018±0.21cm~3, 4.290±0.67cm~3, Significantdifference existed in growth rates among 3 groups (p＜0.01) and between eithergroups(p＜0.01); Significant difference existed in metastasis of livers 1cm around tumoramong 3 groups (p＜0.01), but not between B and C (p＞0.05).
Conclusion Arterial Embolization of thermosensitve poly nanogel had markedinhibitory effect on rabbit VX2 transplanted hepatocarcinoma, and is an ideal embolizationagent for hepatocarcinoma.
目的研究新型栓塞剂温敏型聚(N—异丙基丙烯酰胺—co—甲基丙烯酸丁酯)纳米凝胶(简称温敏纳米凝胶)的相关特性及其作为血管栓塞剂的有效性、安全性。
材料与方法对温敏纳米凝胶进行一系列有关特性的鉴定，并分别进行体外模拟实验及10只家兔肝动脉栓塞实验，另10只用生理盐水注入肝动脉作对照。结果温敏纳米凝胶为温度敏感性栓塞材料，常温下流动性好，呈液体状态，37℃时完全凝固，失去流动性，且具有高触变性，易经导管注射；具有良好的血液相容性和组织相容性，无致热原性及毒性作用；栓塞部位主要是末梢小动脉；经光镜观察其对正常肝组织损伤轻微，仅出现栓塞部位的肝细胞变性和坏死。
结论温敏纳米凝胶使用方便、安全，是一种较理想的末梢型血管栓塞剂。可用于进一步动物实验。
第二部分温敏纳米凝胶栓塞正常家兔肾动脉的栓塞实验研究
目的应用温敏纳米凝胶栓塞家兔的肾动脉及肝动脉，探讨温敏纳米凝胶作为血管栓塞剂的可行性。
材料与方法60只新西兰大白兔，分别用温敏纳米凝胶栓塞右肾动脉及肝动脉，并用PVA栓塞右肾动脉作对照，术后观查家兔一般情况、存活时间、肝功能及病理改变。
结果温敏纳米凝胶为温度敏感性栓塞材料，易经介入导管注射，栓塞后家兔精神、饮食正常，肾功能14天可恢复正常；凝胶可根据需要栓塞各级动脉，栓塞末梢血管牢固，时间达两月以上；栓塞后家兔无明显毒副反应；病理检查右肾动脉栓塞后3天即出现梗死，肝组织14天后出现坏死；35天后被凝胶栓塞的肝组织及肾组织均出现弥漫性坏死。
结论温敏纳米凝胶使用方便、安全，栓塞血管效果好，是一种较理想的血管栓塞剂。
第三部分温敏纳米凝胶对兔VX2移植性肝癌栓塞效果的实验研究
实验一用于介入栓塞剂研究的肝癌模型的建立
目的建立兔VX2移植性肝癌模型、探讨其影像学及病理学特点。
材料与方法将50只新西兰大白兔采用移植法建立兔VX2移植性肝癌模型，于移植术后13天行DSA、MRI、CT及病理检查。
结果有48只兔接种成功，其影像学及病理学表现均类似于人类原发性肝癌。
结论兔VX2移植性肝癌模型可用于血管栓塞剂温敏纳米凝胶的实验研究。
实验二温敏纳米凝胶介入栓塞治疗兔VX2移植性肝癌的疗效
目的评价温敏纳米凝胶介入栓塞治疗兔VX2移植性肝癌的疗效。
材料和方法将45只新西兰大白兔采用移植法建立移植性肝癌模型，于移植术后13天后行MRI检查，测量肿瘤体积(V1)，再随机分成3组，A组：经肝动脉注入温敏纳米凝胶0.6ml；B组：经肝动脉灌注超液态碘油0.6ml+0.25mg明胶海绵粉；C组：经肝动脉灌注生理盐水1ml。14天后再行磁共振检查以确定肿瘤体积(V2)，对三组间肿瘤生长率(V2／V1)进行比较。先进行大体标本观察，包括肿瘤大小、坏死、出血情况。镜下组织学观察肿瘤细胞排列方式、坏死及肝内转移等。
结果A、B、C三组间肿瘤生长速率不完全相同，肿瘤大小术前分别为0.068±0.11cm~3，0.071±0.23 cm~3，0.069±0.19 cm~3；术后14天分别为0.289±0.18cm~3，1.018±0.21cm~3，4.290±0.67cm~3，术后三组间肿瘤体积有显著性差异(p＜0.01)，两两比较各组间均有显著性差异(p＜0.01)；各组间肝表面转移灶及显微镜下瘤周1cm肝组织转移灶不完全相同，两两比较示A组与B组、A组与C组均存在显著性差异(p＜0.01)，而B、C两组无统计学差异(p＞0.05)。
结论温敏纳米凝胶的栓塞治疗对兔VX2移植性肝癌具有显著的生长抑制作用，是一种较理想的肝癌栓塞物质
Part oneStudy on the Characteristics of Thermosensitve Poly Nanogel
Objective To study the correlation properties of thermosensitve poly (N-isopropylacrylamide- co-butyl methacrylate) nanogel and the efficacy, safety andcorrelative characteristics as a vascular embolization agent.
Materials and methods Related characteristics of thermosensitve poly nanogel werestudied. Extra corporeal simulation experiments and hepatic arterial embolization of 10rabbits were performed with thermosensitve poly nanogel respectively, others 10 rabbitsembolized with Normal saline as a control.
Results Thermosensitve poly nanogel is a thermosensitive embolic material in liquid statewith fine fluidity at room temperatrue, fully solidifies at 37℃and loses fluidity, having ahigh thixotropy and being easily injected through all sorts of interventional catheters andthe embolization agent has hemo-compatibility and good histocompat- ibility, withoutpyrogenetic response and toxicity. Thermosensitve poly nanogel mainly embolized theperipheral arteries. Slight injuries of normal hepatic tissues with hepatic cytonecrosisandendochyloma focal necrosis were found through electronic microscopy.
Conclusion Thermosensitve poly nanogel is a safe and effective peripheral embolizationagent in experimental application and a and may be confirmed in further animalexperiments.
Part twoThe Animal experimental study On the Vascular Embolization Agent ofThermosensitve Poly Nanogel
objective To emblazc the right renal artery and the hepatic arterial of rabbits withthermosensitve poly nanogel and investigate its feasibility as a vascular embolization agent.
Materials and methods To emblize the right renal artery the hepatic arterial of 60 rabbitswith thermosensitvc poly nanogel, PVA as a control. General condition, survival time,hepatic and renal function and pathological changes of the rabbits treated byThermosensitve poly nanogel were performed. Follow-up angiography was performed forembolic efficacy.
Results Thermosensitve poly nanogel which easily injected through all sorts ofinterventional catheters is a thermosensitive embolic material. The spirit, drink, eating,hepatic function were normal after embolization and renal function could get normal after14 days. Thermosensitve poly nanogel could emblize arteries at all levels according toexperimental need and could emblaze the periphcral arteries firmly with maintainingocclusion for over one month without pyrogenetic response and toxicity. Pathologically,infarction of renal tissuc was found 3 days after the right renal were embolized,whilehepatic tissue necrosis was found 14days after the hepatic were embolized and diffusenecrosis of renal and hepatic tissue was found 35 days after operation.
Conclusion Thermosensitve poly nanogel is a safe and convincnt embolization agentwith good angiocmbolic function and is an ideal vascular embolization agent.
Part threeTreatment effect of Thermosensitve Poly Nanogel for Rabbit VX2transplanted hepatocarcinoma model
Test 1 Establishing Rrabbit transplanted VX2 hepatocarcinoma modelfor study of Vascular embolization agent
Objective To establish the rabbit VX2 hepatocarcinoma model and study the features ofimaging and pathology examination.
Materials and methods Fifty Newzealand rabbits hepatocarcinoma model wereestablished by VX2 tumor implantation, Digital subtraction angiography(DSA), magneticresonance imaging(MRI), computed tomography(CT) scanning and Pathology wereperformed 13 days after implantation.
Result Succecssful implantation was obtained in 38 rabbits by the examination ofMRI.The imagology and pathology are all similar with human hepatocarcinoma.
Conclusion Rabbit VX2 heptocarcinoma model is suitable for interventional experimentstudy of the vascular embolization agent of thermosensitve poly nanogel onhepatocarcinoma.
Test 2 Treatment effect of Thermosensitve Poly Nanogel for Rabbit VX2transplanted hepatocarcinoma model
objective To observe the inhibiting effect of thermosensitve poly nanogel on rabbit VX2transplanted hepatocarcinoma model through emblazing hepatic artery.
Materials and methods 45 rabbits hepatoma model were established by VX2 tumorimplantation.The tumor volume (V1) was measured by magnetic resonance imaging 13days after implantation, then the rabbits were splited randomly into three group(n=15).Andafter 14 days thermosensitve poly nanogel 0.6ml,ultrofluid lipiodol 0.6ml and 0.25mggelfoam spong, Normal saline 1 ml were infused though hepatic artery respectively. Afteranother 14days MRI were performed once again to determine the tumor volume and Thetumor growth rates of three groups were compared. Gross specimen were performedfirstly, including tumor size, necrosis, hemorrhage and liver surface metastases and thearrangement of tumor cells, necrosis and intrahepatic metastasis were observed throughhistological observation under a microscope.
Results Average tumor volume of the three groups before operation were0.068±0.11cm~3, 0.071±0.23 cm~3, 0.069±0.19 cm~3, while after operation, average tumorvolume of the three group were 0.289±0.18cm~3, 1.018±0.21cm~3, 4.290±0.67cm~3, Significantdifference existed in growth rates among 3 groups (p＜0.01) and between eithergroups(p＜0.01); Significant difference existed in metastasis of livers 1cm around tumoramong 3 groups (p＜0.01), but not between B and C (p＞0.05).
Conclusion Arterial Embolization of thermosensitve poly nanogel had markedinhibitory effect on rabbit VX2 transplanted hepatocarcinoma, and is an ideal embolizationagent for hepatocarcinoma.
引文
1．王勇，张永海，刘建行等。多柔比星磁性葡聚糖微球的制备及特性检测。中国药师，2006， 9(12)：1089-1091
2．张志清，扬秀岭，孙莉等．依托泊苷白蛋白微球的制备。中国药学杂志，2000，35(3)：171-173
3．冯敢生，郑传胜，周汝明等。白芨与明胶海绵治疗肝癌疗效的对比研究．中华放射学杂志，1996，30(2)：135-137
4. HeskinsM, Guillet JE. Solution p roperties of poly (N - isop ropylac- rylamide) [J].J Macrono Sci Chem, 1968,A (2) : 1441-1455
5. Dorkeosh F, Coos Vef J, Ambagls MH. Peroral delivery systems based on supexporous hydrogel polymers: release characterization for peptide drugs buserelin octreotide and insulin[J]. Eur Pharm Sci, 2002, 15(5): 433
6．吴道澄，万明习，吴红．智能化释药载体纳米凝胶的制备及其释药特性[J]．第四军医大学学报，2001，22(8)：767
7．盛希忠，刘作勤，武乐斌等。温度敏感型液体栓塞材料的动物实验研究．中华神经外科杂志，200，22(2)：123-126
8. Peppas NA, Bures P, Leobandung W, et al. Hydrogels in pharmaceutical formulation[J]. Eur J pharm, Biopharm, 2000, 50(1): 27
9．赵强，庞小峰．磁性纳米生物材料研究进展及其应用[J]．原子与分子物理学报，2005，22(2)：222-225
10. Ichikawa H, Fukumori Y. Design of nanohydrogel-incorporated microcapsules for appropriate controlled-release of peptide drugs. Yakugaku Zasshi,2007,127(5):813-823
11. Yoshida R. Controlled release using temperature-responsive poly(N-isopropylacrylamide) gel. Nippon Rinsho. 1998,56(3):670-674
12. Shin Y, Chang JH, Liu J, Williford R,et al. Hybrid nanogels for sustainable positive thermosensitive drug release. J Control Release. 2001,73(1):1-6
13. Y.Zhao, Y. Cao, Y. L. Yang, et al.Rheological study of the sol-gel transition of hybrid gels. Macromolecules, 2003, 36(3): 855-859
14. Ichikawa H, Fukumori Y. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2):107-119
1．王芹，徐辉碧，杨祥良等。可显影原位凝胶化温敏纳米凝胶的制备及性能。医药导报，2008，27(10)：3421-7421
2．郑传胜，冯敢生，周汝明等。中药白芨的新用途。中华肿瘤杂志，1996，18(4)：305-307
3．张志清，扬秀岭，孙莉等．依托泊苷白蛋白微球的制备。中国药学杂志，2000，35(3)：171-173
4．冯敢生，郑传胜，周汝明等。白芨与明胶海绵治疗肝癌疗效的对比研究．中华放射学杂志，1996，30(2)：135-137
5. HeskinsM, Guillet JE. Solution p roperties of poly (N - isop ropylac- rylamide). J Macrono Sci Chem, 1968,A (2) : 1441 - 1455
6．盛希忠，刘作勤，武乐斌等。 温度敏感型液体栓塞材料的动物实验研究．中华神经外科杂志，2006，22(2)：123-126
7. Zhang J,Chen H,Xu L, Gu Y.The targeted behavior of thermally responsive nanohydrogel evaluated by NIR system in mouse model. J Control Release.2008,131(1):34-40
8. Ichikawa H, Fukumori Y. Design of nanohydrogel-incorporated microcapsules for appropriate controlled-release of peptide drugs. Yakugaku Zasshi, 2007,127(5):813-823
9. Riwako Nakamoto ,Ryoji Yasue. Effect of the particle size on the rheology of Gellan Gum microgel. Nihon Reoroji Gakkaishi, 2003 (31): 337-342
10. Y.Zhao, Y. Cao, Y. L. Yang, et al. Rheological study of the sol-gel transition of hybrid gels. Macromolecules, 2003, 36(3): 855-859
11. Ichikawa H, Fukumori Y. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N -isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2):107-119
12. Mathurin P;Durand F;Ganne N,et al. Ischemic hepatitis due to obstructive sleep apnea. Gastroenterology 1995,10;109(5):1682-1684
1．王 芹，徐辉碧，杨祥良等。可显影原位凝胶化温敏纳米凝胶的制备及性能。医药导报，2008，27(10)：3421-7421
2．盛希忠，刘作勤，武乐斌等。温度敏感型液体栓塞材料的动物实验研究．中华神经外科杂志，200，22(2)：123-126
3．李欣，冯敢生，郑传胜等。经肝动脉注射5-FU白芨微球治疗兔VX2移植性肝癌。世界华人消化杂志，2003，11(9)：1337-1340
4．贾洪颅，全显跃．改进兔肝动脉插管术：肝血管影像研究[J]．放射学实践，2002，17(4)：324-326
5. Mihmanli I,Cantasdemir M,Kantarci F, et al.Percutaneous embolization in the management of intractable vaginal bleeding.Arch gynecol Obstet, 2001, 264(4):211-214
6. Kwak BK, Shim HJ,Han SM,et al.Chitin-based embolic materials in the renal artery of rabbits:pathologic evaluation of an absorbable particulate agent, Radiology,2005, 236(1):151-158
7. Taki W, Yonekawa Y, lwata H,et ,al.A liquid material for embolization of arteriovenous malformations.AJNR Am J Neuroradiol 1990,11(1):163-168
8. Ichikawa H, Fukumori Y. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2):107-119
9. R. Nakamoto, et al. Effect of the particle size on the theology of Gellan Gum microgel. Nihon Reoroji Gakkaishi, 2003 (31): 337-342
10. Y.Zhao, Y. Cao, Y. L. Yang, et al.Rheological study of the sol-gel transition of hybrid gels. Macromolecules, 2003, 36(3): 855-859
11. Ichikawa H, Fukumori Y. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2):107-119
12. Link DP,strandberg JD,Virmani R,et al. Histopathologic appearance of arterial occlusions with hydrogel and polyvinyl alcohol embolic material in domestic swine.. J Vasc Interv Radiol. 1996 ,7(6):897-905
13. Germano IM,Davis RL,Wilson CB,et al. Histopathological follow-up study of 66 cerebral arteriovenous malformations after therapeutic embolization with polyvinyl alcohol.. J Neurosurg. 1992,76(4):607-614
14. Mathurin P;Durand F;Ganne N,et al. Ischemic hepatitis due to obstructive sleep apnea. Gastroenterology 1995,10;109(5):1682-1684
1．李欣，郑传胜，冯敢生，等．移植性大鼠肝癌模型肝动脉栓塞前后的影像学特征与病理分析。临床放射学杂志，2002，21(8)：239-242
2. Yang R, Rescorla F, Reilly C, et al. Areproducible rat liver cancer model for experimental therapy : introducing a technique of intrahepatic tumor implantntion.J Surg Res, 1992, 52(8): 193-198
3．凌昌全，李琦，刘晓华等。经动脉灌注蜂毒素-聚乳酸／羟乙酸微球治疗大鼠肝肿瘤。 世界华人消化杂志 2003；11(7)：900-903
4. Kuszyk BS, Boitnott JK, Choti MA, et al. Local tumor recurrence following hepatic cryoablation:radiologic-histopathologic correlationin a rabbit model [J] .Radiology,2000,217(2):477-486
5. Geschwind JF, Artemov D, Abraham S, et al. Chemoembolization ofliver tumor in a rabbit model: assessment of tumor cell death with diffusion-weighted MR imaging and histologic analysis [J] . J Vasclnterv Radiol,2000,11(10):1245-1265
6. Miao Y, Ni Y, Bosmans H, et al. Radiofrequency ablation for eradication of renal tumor in a rabbit model by using a cooled-tip electrode technique. Ann Surg Oncol ,2001,8(8) : 651-657
7. JKuwata Y, Hirota S,Sako M.Treatment of metastatic liver tumors by intermittent repetitive injection of an angiogenesis inhibitor using an implantable port system in a rabbit model[J]. Kobe J Med Sci,1997,43(2):83-85
8．邵国良，周康荣，王建华，等．介入治疗实验研究中兔VX2肝癌模型制作的改进和CT评价[J]．临床放射学杂志，20000，19(10)：653-655
9. Hansler J, Neureiter D, Wasserburger M, et al. Pereutaneous US-guided radiofrequency ablation with perfused needle applicators: improved survival with the VX2 tumor model in rabbits[j]. Radiology, 2004, 230(1): 169-174
10. Liu X, Li X, Zhao JG, et al. Making rabbit model with VX2 liver tumor and multiple imaging evaluation[J]. J Pract Radiol, 2002, 18 (2): 132-134
11．贾洪顺，全显跃，曾盛，等．兔VXZ肝癌CT、MRI动态评价[J]．第一军医大学学报，2002，22(2)：141-143
12. Hanahan D, Folkman J.Patterns and emergings mechanisms of the angiogenics witch during tumorigenesis.ce Ⅱ ,1996,86(3):353-355
1．王增寿，胡伟，张华等。多柔比星壳聚糖微球的制备及其特性研究。医药导报，26(7)：720-723
2．杨国华 陈孝平 黄志勇。纳米羟基磷灰石碘油混合物栓塞治疗兔VX2肝肿瘤。中华实验外科杂志，2007，24(3)，288-289
3．盛希忠，刘作勤，武乐斌等。 温度敏感型液体栓塞材料的动物实验研究．中华神经外科杂志，2006，22(2)：123-126
4. Wang Q, Xu H, Yang X,et,al. Drug release behavior from in situ gelatinized therrnosensitive nanogel aqueous dispersions. Int J Pharm. 2008,361(1-2):189-193
5. Shin Y, Chang JH, Liu J,et al. Hybrid nanogels for sustainable positive thermosensitive drug release. J Control Release. 2001,73(1):1-6
6. Riwako Nakamoto ,Ryoji Yasue. Effect of the particle size on the rheology of Gellan Gum microgel. Nihon Reoroji Gakkaishi, 2003 (31): 337-342
7. Liu XM, Yang YY, Leong KW. Thermally responsive polymeric micellar nanoparticles self-assembled from cholesteryl end-capped random poly(N-isopropylacrylamide-co-N,N-dimethylacryiamide): synthesis,temperature-sensitivity, and morphologies. J Colloid Interface Sci.2003,266(2):295 -303
8. Ichikawa H, Fukumori Y. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2):107-119
9. Moroz P, Jones SK, Winter J, et al. Targeting hver tunlor8 tith by perthermia:ferromagnetic embolization in a rabbit liver tunlor model [J], J Surg Oncol, 2001,78(1): 30-31
10. Tanaka S, Fujihara A, Yamamoto M, et al.Antitumor activity of zinostatin stimalamer (YM881) in human hepatoma cell lines and VX2 liver tumor-bearing rabbits. Res Commun Mol Pathol Pharmacol. 1996,92(2): 155-163
11. Lee KH, Liapi E, Buijs M, et al.J Vasc Interv Radiol. 2009,20(1):113-117
12. Zhong L, Yu ZJ, Quan XY. Preparation of VX2 rabbit hepatoma models and modification of the hepatic artery catheterization technique. Nan Fang Yi Ke Da Xue Xue Bao. 2008,28(9):1654-1659
13．李欣，郑传胜，冯敢生等。化疗栓塞后VEGF的表达及其与微血管密度和细胞增殖关系的实验研究。临床放射学杂志，2004，23(2)：162-165
14．郭琳琅，郭颖，曹长安．原发性肝癌组织中粘附分子CD54，CD44及E-cadherin的表达及意义[J]．中国普通外科杂志，2000，9(5)：424-426
1. Link DP, strandberg JD,Virmani R,et al.Histopathologic appearance of arterial occlusions with hydrogel and polyvinyl alcohol embolic material in domestic swine[J].J Vasc interv Radiol,1996,7(6):897-905
2. Siskin GP, Dowling K, Virmani R, et al. Pathologic evaluation of a spherical polyvinyl alcohol embolic agent in a porcine renal model. J Wasc lnterv Radiol. 2003 Jan;14(1):89-98
3．李海涛，解皓，柴斌等．不同栓塞剂治疗大咯血的对比研究．放射学实践。2007，22(10)：1092-1094
4．朱康顺，单鸿，李征然，等．PVA颗粒作为栓塞材料在部分性脾栓塞术中的应有评价[J]．介入放射学杂志，2004，13(1)：19-22
5．王恺，马光辉。白蛋白微球的制备、改性和应用的研究进展。国外医学药学分册，2003，30(6)，366-371
6．张志清，扬秀岭，孙莉等．依托泊苷白蛋白微球的制备。中国药学杂志，2000，35(3)：171-173
7．冯敢生，郑传胜，周汝明，等．白芨与明胶海绵治疗肝癌疗效的对比研究．中华放射学杂志，1996，30(2)：135-137
8. Molyneux A, Kerr R, Stratton I, et al.International Subarachnoid Aneurysm Trial(ISAT) of neurosurgical clipping versus endovascularcoiling in 2143 patients with ruptured intracranial aneurysms a randomised trial[J]. Lancet,2002,360(9342):1267-1274
9. Tamatani S, Ozawa T, Minakawa T, et al. Histological interaction of cultured endothelial cells and endovascular embolic materials coated with extracellular matrix. J Neurosurg,1997, 86(1): 109-112
10. Murayama Y, Tateshima S,song J K, et al.Bioabsorbable polymeric material coils for embolization of intracranial aneurysms: a preliminary experimental study. J Neurosurg. 2001, 94(3):454-463
11. Muravama Y, Tateshima S, Gonzalez NR, et al. Matrix and bioabsorbable polymeric coils accelerate healing of intracranial aneuDsnls longterm experimental study Stroke. 2003, 34(8): 2031-2037.
12. Phadkc Rv, Kumar s, Sawlani v, el al. Traumatic carotid cavernous fistula :anatomical variations and their treatment by detachable balloons [J]. Australas Radiol,1998,42(1):1-5
13．胡再虎，万经海，李长元，等。a-氰基丙烯酸正丁酯血管内栓塞脑动静脉畸形的临床疗效分析[J]．中国脑血管病杂志，2007，4(2)：87-89
14．俞耀庭，张兴栋．生物医用高分子材料[M]．天津：天津大学出版社，2000
15. Gehrke S H, Palasis M, Akhtar M K. Polym. lnt., 1993, 29(1): 29-35
16. Kokufuta E, Tanaka T. Macromol, 1991, 24(7): 1605-1607
17．王 芹，徐辉碧，杨祥良等。可显影原位凝胶化温敏纳米凝胶的制备及性能。医药导报2008，27(10)：3421-7421
18. Hideki Ichikawa,Yoshinobu Fukumori. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2): 107-119
19. Cao GW , Li GZ, Liu ZX, et al. Clinical research on treatment of hepatocelular carcinoma with transcatheter artery chemoembolization combined with percutan eous ethanol and 32P-glass microspheres in. jection under ultrasound guidance[J]. Chin J Radiol, 1998; 32(10): 667-669
20．信涛，赵玉莹，徐玉清等。阿霉素白蛋白磁性纳米颗粒栓塞治疗大鼠原发性肝癌的实验研究。中国肿瘤临床，2007，34(24)：1422-1427
1．刘志苏，唐胜利，艾中立，等．羟基磷灰石纳米粒子对人肝癌和结肠癌细胞生长的抑制作用，中华实验外科杂志，2006，23(3)：266-268
2．魏世成，李玉宝，郑谦，等．注射型纳米羟基磷灰石，聚酰胺生物活性骨修复材料的研究[J]．生物医学工程学杂志， 2003，20(4)：590-593
3．孙振纲， 陈孝平，黄志勇等．不同剂量的羟基磷灰石纳米微粒治疗兔肝VX2肿瘤的实验研究，腹部外科,2006,19(6)：267-269
4. OORE A, BASILION J P, CHIOCCA E A, et al. Measuring transferrin receptor gene expression by NMR imaging [J]. Biochim Biophys Acta, 1998, 1402(3):239-249
5. Ichikawa H, Fukumori Y. Design of nanohydrogel-incorporated microcapsules for appropriate controlled-release of peptide drugs. Yakugaku Zasshi, 2007, 127(5): 813-823
6. Hideki Ichikawa,Yoshinobu Fukumori. A novel positively thermosensitive Controlled-release microcapsule with membrane of nano-sized poly (N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2): 107-119
7．王 芹，徐辉碧，杨祥良等。可显影原位凝胶化温敏纳米凝胶的制备及性能。医药导报2008，27(10)：3421-7421
8. Yoshida R. Controlled release using temperature-responsive poly (N-isopropylacrylamide) gel. Nippon Rinsho. 1998,56(3):670-674
9. Ilium L. Nanoparticulate systems for nasal delivery of drugs: a real improvement over simple systems .J Pharm Sci. 2007,96(3):473-483
10. Mundargi RC, Babu VR, Rangaswamy V, et al. Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives. J Control Release. 2008,125(3):193-209
11. Tian ZM, Wan MX, Wang B, et al. Efects of ultrasound on the structure and function of tumor necrosis factor-alpha. Ultrasound Med Biol。 2003, 29(9): 1331-1339.
12．张阳德，潘爱华，潘一峰．纳米生物医学工程进展[J]．中国现代医学杂志，2001，11(3)：111-113
13. MeiZhi-nan.experimental research on triptolide solid lipid for nanopartiele decreasing liver toxicity of triptolide.Chinese Traditional and Herbal Drugs, 2003,(9):817-819
14. ZHANG YD,GONG LS.Target distribution of magnetic albumin nanoparticles containing adriamycin in normal liver in rats[J], Chinese Journal of Modem Medicine, 2001; 11(3):4-7
15．刘利萍，吴泽志，李苹，等．天然高分子磁微球作为靶向制剂的研究进展[J]．药物生物技术，2004，11(1)：68-70
16．信涛，赵玉莹，徐玉清等．5可霉素白蛋白磁性纳米颗粒栓塞治疗大鼠原发性肝癌的实验研究．中国肿瘤临床，2007，34(24)：1422-1427
17. Zhu HG, Ji J,Shen JC,et al.Surface engineering of poly (DL-lactide) via electrostatic self-assembly of extracellular matrix-like molecules Biomacromolecules,2003, 4(2): 378-386
18. Thackray AC,Sammons RL, Macaskie LE,et al.Bacterial biosynthesis of a calcium phosphate bone-substitute material.J Mater Sci Mater Med 2004,15(4):403-406
19. Arias JL, Mayor MB, Pou J, et aI.Micro- and nano-testing of calcium phosphate coating produced by pulsed laser deposition.Biomaterials 2003:24(20):3403-3408
20. Hong Y, Gao CY, Shen JC,et al.Collagen-coated polylactide microspheres as chondrocyte microcarriers. Biomaterials, 2005,26(32):6305-6313
21. Zhang SG.Fabrication of novel biomaterials through molecular self-assembly.Nat Biotechnol,2003,21(10):1171-1178
22. Freitas RA Jr. Exploratory design in medical nan0techno10gy: a mechanical artificial red cell[J]. Cells Blood Substit Immobil Biotechnol, 1998, 26(4): 411 -430
23．王国清，钟季康 王保华．纳米技术及其在生物医学中的应用[J]．生物医学工程与临床，2002，6(2)：109-112
24．王 兰．纳米在临床诊断及治疗研究中的进展[J]．中国医师杂志，2002，4(3)：225-226
25. Kasili PM, Vo-Dinh T. Optical nanobiosensor for monitoring an apoptotic signaling process in a single living cell following photo dynamic therapy. J Nanosci Nanotechnol. 2005,5(12):2057-2062
26. Cullum BM, Vo-Dinh T. The development of optical nanosensors for biological measurements. Trends Biotechnol. 2000, 18(9):388-393
27. Zhang YB, Kanungo M, Ho AJ, et,al. Functionalized carbon nanotubes for detecting viral proteins. Nano Lett. 2007,7(10):3086-3091.
2．张志清，扬秀岭，孙莉等．依托泊苷白蛋白微球的制备。中国药学杂志，2000，35(3)：171-173
3．冯敢生，郑传胜，周汝明等。白芨与明胶海绵治疗肝癌疗效的对比研究．中华放射学杂志，1996，30(2)：135-137
4. HeskinsM, Guillet JE. Solution p roperties of poly (N - isop ropylac- rylamide) [J].J Macrono Sci Chem, 1968,A (2) : 1441-1455
5. Dorkeosh F, Coos Vef J, Ambagls MH. Peroral delivery systems based on supexporous hydrogel polymers: release characterization for peptide drugs buserelin octreotide and insulin[J]. Eur Pharm Sci, 2002, 15(5): 433
6．吴道澄，万明习，吴红．智能化释药载体纳米凝胶的制备及其释药特性[J]．第四军医大学学报，2001，22(8)：767
7．盛希忠，刘作勤，武乐斌等。温度敏感型液体栓塞材料的动物实验研究．中华神经外科杂志，200，22(2)：123-126
8. Peppas NA, Bures P, Leobandung W, et al. Hydrogels in pharmaceutical formulation[J]. Eur J pharm, Biopharm, 2000, 50(1): 27
9．赵强，庞小峰．磁性纳米生物材料研究进展及其应用[J]．原子与分子物理学报，2005，22(2)：222-225
10. Ichikawa H, Fukumori Y. Design of nanohydrogel-incorporated microcapsules for appropriate controlled-release of peptide drugs. Yakugaku Zasshi,2007,127(5):813-823
11. Yoshida R. Controlled release using temperature-responsive poly(N-isopropylacrylamide) gel. Nippon Rinsho. 1998,56(3):670-674
12. Shin Y, Chang JH, Liu J, Williford R,et al. Hybrid nanogels for sustainable positive thermosensitive drug release. J Control Release. 2001,73(1):1-6
13. Y.Zhao, Y. Cao, Y. L. Yang, et al.Rheological study of the sol-gel transition of hybrid gels. Macromolecules, 2003, 36(3): 855-859
14. Ichikawa H, Fukumori Y. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2):107-119
1．王芹，徐辉碧，杨祥良等。可显影原位凝胶化温敏纳米凝胶的制备及性能。医药导报，2008，27(10)：3421-7421
2．郑传胜，冯敢生，周汝明等。中药白芨的新用途。中华肿瘤杂志，1996，18(4)：305-307
3．张志清，扬秀岭，孙莉等．依托泊苷白蛋白微球的制备。中国药学杂志，2000，35(3)：171-173
4．冯敢生，郑传胜，周汝明等。白芨与明胶海绵治疗肝癌疗效的对比研究．中华放射学杂志，1996，30(2)：135-137
5. HeskinsM, Guillet JE. Solution p roperties of poly (N - isop ropylac- rylamide). J Macrono Sci Chem, 1968,A (2) : 1441 - 1455
6．盛希忠，刘作勤，武乐斌等。 温度敏感型液体栓塞材料的动物实验研究．中华神经外科杂志，2006，22(2)：123-126
7. Zhang J,Chen H,Xu L, Gu Y.The targeted behavior of thermally responsive nanohydrogel evaluated by NIR system in mouse model. J Control Release.2008,131(1):34-40
8. Ichikawa H, Fukumori Y. Design of nanohydrogel-incorporated microcapsules for appropriate controlled-release of peptide drugs. Yakugaku Zasshi, 2007,127(5):813-823
9. Riwako Nakamoto ,Ryoji Yasue. Effect of the particle size on the rheology of Gellan Gum microgel. Nihon Reoroji Gakkaishi, 2003 (31): 337-342
10. Y.Zhao, Y. Cao, Y. L. Yang, et al. Rheological study of the sol-gel transition of hybrid gels. Macromolecules, 2003, 36(3): 855-859
11. Ichikawa H, Fukumori Y. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N -isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2):107-119
12. Mathurin P;Durand F;Ganne N,et al. Ischemic hepatitis due to obstructive sleep apnea. Gastroenterology 1995,10;109(5):1682-1684
1．王 芹，徐辉碧，杨祥良等。可显影原位凝胶化温敏纳米凝胶的制备及性能。医药导报，2008，27(10)：3421-7421
2．盛希忠，刘作勤，武乐斌等。温度敏感型液体栓塞材料的动物实验研究．中华神经外科杂志，200，22(2)：123-126
3．李欣，冯敢生，郑传胜等。经肝动脉注射5-FU白芨微球治疗兔VX2移植性肝癌。世界华人消化杂志，2003，11(9)：1337-1340
4．贾洪颅，全显跃．改进兔肝动脉插管术：肝血管影像研究[J]．放射学实践，2002，17(4)：324-326
5. Mihmanli I,Cantasdemir M,Kantarci F, et al.Percutaneous embolization in the management of intractable vaginal bleeding.Arch gynecol Obstet, 2001, 264(4):211-214
6. Kwak BK, Shim HJ,Han SM,et al.Chitin-based embolic materials in the renal artery of rabbits:pathologic evaluation of an absorbable particulate agent, Radiology,2005, 236(1):151-158
7. Taki W, Yonekawa Y, lwata H,et ,al.A liquid material for embolization of arteriovenous malformations.AJNR Am J Neuroradiol 1990,11(1):163-168
8. Ichikawa H, Fukumori Y. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2):107-119
9. R. Nakamoto, et al. Effect of the particle size on the theology of Gellan Gum microgel. Nihon Reoroji Gakkaishi, 2003 (31): 337-342
10. Y.Zhao, Y. Cao, Y. L. Yang, et al.Rheological study of the sol-gel transition of hybrid gels. Macromolecules, 2003, 36(3): 855-859
11. Ichikawa H, Fukumori Y. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2):107-119
12. Link DP,strandberg JD,Virmani R,et al. Histopathologic appearance of arterial occlusions with hydrogel and polyvinyl alcohol embolic material in domestic swine.. J Vasc Interv Radiol. 1996 ,7(6):897-905
13. Germano IM,Davis RL,Wilson CB,et al. Histopathological follow-up study of 66 cerebral arteriovenous malformations after therapeutic embolization with polyvinyl alcohol.. J Neurosurg. 1992,76(4):607-614
14. Mathurin P;Durand F;Ganne N,et al. Ischemic hepatitis due to obstructive sleep apnea. Gastroenterology 1995,10;109(5):1682-1684
1．李欣，郑传胜，冯敢生，等．移植性大鼠肝癌模型肝动脉栓塞前后的影像学特征与病理分析。临床放射学杂志，2002，21(8)：239-242
2. Yang R, Rescorla F, Reilly C, et al. Areproducible rat liver cancer model for experimental therapy : introducing a technique of intrahepatic tumor implantntion.J Surg Res, 1992, 52(8): 193-198
3．凌昌全，李琦，刘晓华等。经动脉灌注蜂毒素-聚乳酸／羟乙酸微球治疗大鼠肝肿瘤。 世界华人消化杂志 2003；11(7)：900-903
4. Kuszyk BS, Boitnott JK, Choti MA, et al. Local tumor recurrence following hepatic cryoablation:radiologic-histopathologic correlationin a rabbit model [J] .Radiology,2000,217(2):477-486
5. Geschwind JF, Artemov D, Abraham S, et al. Chemoembolization ofliver tumor in a rabbit model: assessment of tumor cell death with diffusion-weighted MR imaging and histologic analysis [J] . J Vasclnterv Radiol,2000,11(10):1245-1265
6. Miao Y, Ni Y, Bosmans H, et al. Radiofrequency ablation for eradication of renal tumor in a rabbit model by using a cooled-tip electrode technique. Ann Surg Oncol ,2001,8(8) : 651-657
7. JKuwata Y, Hirota S,Sako M.Treatment of metastatic liver tumors by intermittent repetitive injection of an angiogenesis inhibitor using an implantable port system in a rabbit model[J]. Kobe J Med Sci,1997,43(2):83-85
8．邵国良，周康荣，王建华，等．介入治疗实验研究中兔VX2肝癌模型制作的改进和CT评价[J]．临床放射学杂志，20000，19(10)：653-655
9. Hansler J, Neureiter D, Wasserburger M, et al. Pereutaneous US-guided radiofrequency ablation with perfused needle applicators: improved survival with the VX2 tumor model in rabbits[j]. Radiology, 2004, 230(1): 169-174
10. Liu X, Li X, Zhao JG, et al. Making rabbit model with VX2 liver tumor and multiple imaging evaluation[J]. J Pract Radiol, 2002, 18 (2): 132-134
11．贾洪顺，全显跃，曾盛，等．兔VXZ肝癌CT、MRI动态评价[J]．第一军医大学学报，2002，22(2)：141-143
12. Hanahan D, Folkman J.Patterns and emergings mechanisms of the angiogenics witch during tumorigenesis.ce Ⅱ ,1996,86(3):353-355
1．王增寿，胡伟，张华等。多柔比星壳聚糖微球的制备及其特性研究。医药导报，26(7)：720-723
2．杨国华 陈孝平 黄志勇。纳米羟基磷灰石碘油混合物栓塞治疗兔VX2肝肿瘤。中华实验外科杂志，2007，24(3)，288-289
3．盛希忠，刘作勤，武乐斌等。 温度敏感型液体栓塞材料的动物实验研究．中华神经外科杂志，2006，22(2)：123-126
4. Wang Q, Xu H, Yang X,et,al. Drug release behavior from in situ gelatinized therrnosensitive nanogel aqueous dispersions. Int J Pharm. 2008,361(1-2):189-193
5. Shin Y, Chang JH, Liu J,et al. Hybrid nanogels for sustainable positive thermosensitive drug release. J Control Release. 2001,73(1):1-6
6. Riwako Nakamoto ,Ryoji Yasue. Effect of the particle size on the rheology of Gellan Gum microgel. Nihon Reoroji Gakkaishi, 2003 (31): 337-342
7. Liu XM, Yang YY, Leong KW. Thermally responsive polymeric micellar nanoparticles self-assembled from cholesteryl end-capped random poly(N-isopropylacrylamide-co-N,N-dimethylacryiamide): synthesis,temperature-sensitivity, and morphologies. J Colloid Interface Sci.2003,266(2):295 -303
8. Ichikawa H, Fukumori Y. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2):107-119
9. Moroz P, Jones SK, Winter J, et al. Targeting hver tunlor8 tith by perthermia:ferromagnetic embolization in a rabbit liver tunlor model [J], J Surg Oncol, 2001,78(1): 30-31
10. Tanaka S, Fujihara A, Yamamoto M, et al.Antitumor activity of zinostatin stimalamer (YM881) in human hepatoma cell lines and VX2 liver tumor-bearing rabbits. Res Commun Mol Pathol Pharmacol. 1996,92(2): 155-163
11. Lee KH, Liapi E, Buijs M, et al.J Vasc Interv Radiol. 2009,20(1):113-117
12. Zhong L, Yu ZJ, Quan XY. Preparation of VX2 rabbit hepatoma models and modification of the hepatic artery catheterization technique. Nan Fang Yi Ke Da Xue Xue Bao. 2008,28(9):1654-1659
13．李欣，郑传胜，冯敢生等。化疗栓塞后VEGF的表达及其与微血管密度和细胞增殖关系的实验研究。临床放射学杂志，2004，23(2)：162-165
14．郭琳琅，郭颖，曹长安．原发性肝癌组织中粘附分子CD54，CD44及E-cadherin的表达及意义[J]．中国普通外科杂志，2000，9(5)：424-426
1. Link DP, strandberg JD,Virmani R,et al.Histopathologic appearance of arterial occlusions with hydrogel and polyvinyl alcohol embolic material in domestic swine[J].J Vasc interv Radiol,1996,7(6):897-905
2. Siskin GP, Dowling K, Virmani R, et al. Pathologic evaluation of a spherical polyvinyl alcohol embolic agent in a porcine renal model. J Wasc lnterv Radiol. 2003 Jan;14(1):89-98
3．李海涛，解皓，柴斌等．不同栓塞剂治疗大咯血的对比研究．放射学实践。2007，22(10)：1092-1094
4．朱康顺，单鸿，李征然，等．PVA颗粒作为栓塞材料在部分性脾栓塞术中的应有评价[J]．介入放射学杂志，2004，13(1)：19-22
5．王恺，马光辉。白蛋白微球的制备、改性和应用的研究进展。国外医学药学分册，2003，30(6)，366-371
6．张志清，扬秀岭，孙莉等．依托泊苷白蛋白微球的制备。中国药学杂志，2000，35(3)：171-173
7．冯敢生，郑传胜，周汝明，等．白芨与明胶海绵治疗肝癌疗效的对比研究．中华放射学杂志，1996，30(2)：135-137
8. Molyneux A, Kerr R, Stratton I, et al.International Subarachnoid Aneurysm Trial(ISAT) of neurosurgical clipping versus endovascularcoiling in 2143 patients with ruptured intracranial aneurysms a randomised trial[J]. Lancet,2002,360(9342):1267-1274
9. Tamatani S, Ozawa T, Minakawa T, et al. Histological interaction of cultured endothelial cells and endovascular embolic materials coated with extracellular matrix. J Neurosurg,1997, 86(1): 109-112
10. Murayama Y, Tateshima S,song J K, et al.Bioabsorbable polymeric material coils for embolization of intracranial aneurysms: a preliminary experimental study. J Neurosurg. 2001, 94(3):454-463
11. Muravama Y, Tateshima S, Gonzalez NR, et al. Matrix and bioabsorbable polymeric coils accelerate healing of intracranial aneuDsnls longterm experimental study Stroke. 2003, 34(8): 2031-2037.
12. Phadkc Rv, Kumar s, Sawlani v, el al. Traumatic carotid cavernous fistula :anatomical variations and their treatment by detachable balloons [J]. Australas Radiol,1998,42(1):1-5
13．胡再虎，万经海，李长元，等。a-氰基丙烯酸正丁酯血管内栓塞脑动静脉畸形的临床疗效分析[J]．中国脑血管病杂志，2007，4(2)：87-89
14．俞耀庭，张兴栋．生物医用高分子材料[M]．天津：天津大学出版社，2000
15. Gehrke S H, Palasis M, Akhtar M K. Polym. lnt., 1993, 29(1): 29-35
16. Kokufuta E, Tanaka T. Macromol, 1991, 24(7): 1605-1607
17．王 芹，徐辉碧，杨祥良等。可显影原位凝胶化温敏纳米凝胶的制备及性能。医药导报2008，27(10)：3421-7421
18. Hideki Ichikawa,Yoshinobu Fukumori. A novel positively thermosensitive controlled-release microcapsule with membrane of nano-sized poly(N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2): 107-119
19. Cao GW , Li GZ, Liu ZX, et al. Clinical research on treatment of hepatocelular carcinoma with transcatheter artery chemoembolization combined with percutan eous ethanol and 32P-glass microspheres in. jection under ultrasound guidance[J]. Chin J Radiol, 1998; 32(10): 667-669
20．信涛，赵玉莹，徐玉清等。阿霉素白蛋白磁性纳米颗粒栓塞治疗大鼠原发性肝癌的实验研究。中国肿瘤临床，2007，34(24)：1422-1427
1．刘志苏，唐胜利，艾中立，等．羟基磷灰石纳米粒子对人肝癌和结肠癌细胞生长的抑制作用，中华实验外科杂志，2006，23(3)：266-268
2．魏世成，李玉宝，郑谦，等．注射型纳米羟基磷灰石，聚酰胺生物活性骨修复材料的研究[J]．生物医学工程学杂志， 2003，20(4)：590-593
3．孙振纲， 陈孝平，黄志勇等．不同剂量的羟基磷灰石纳米微粒治疗兔肝VX2肿瘤的实验研究，腹部外科,2006,19(6)：267-269
4. OORE A, BASILION J P, CHIOCCA E A, et al. Measuring transferrin receptor gene expression by NMR imaging [J]. Biochim Biophys Acta, 1998, 1402(3):239-249
5. Ichikawa H, Fukumori Y. Design of nanohydrogel-incorporated microcapsules for appropriate controlled-release of peptide drugs. Yakugaku Zasshi, 2007, 127(5): 813-823
6. Hideki Ichikawa,Yoshinobu Fukumori. A novel positively thermosensitive Controlled-release microcapsule with membrane of nano-sized poly (N-isopropylacrylamide) gel dispersed in ethylcellulose matrix. Journal of Controlled Release, 2000, 63(1-2): 107-119
7．王 芹，徐辉碧，杨祥良等。可显影原位凝胶化温敏纳米凝胶的制备及性能。医药导报2008，27(10)：3421-7421
8. Yoshida R. Controlled release using temperature-responsive poly (N-isopropylacrylamide) gel. Nippon Rinsho. 1998,56(3):670-674
9. Ilium L. Nanoparticulate systems for nasal delivery of drugs: a real improvement over simple systems .J Pharm Sci. 2007,96(3):473-483
10. Mundargi RC, Babu VR, Rangaswamy V, et al. Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives. J Control Release. 2008,125(3):193-209
11. Tian ZM, Wan MX, Wang B, et al. Efects of ultrasound on the structure and function of tumor necrosis factor-alpha. Ultrasound Med Biol。 2003, 29(9): 1331-1339.
12．张阳德，潘爱华，潘一峰．纳米生物医学工程进展[J]．中国现代医学杂志，2001，11(3)：111-113
13. MeiZhi-nan.experimental research on triptolide solid lipid for nanopartiele decreasing liver toxicity of triptolide.Chinese Traditional and Herbal Drugs, 2003,(9):817-819
14. ZHANG YD,GONG LS.Target distribution of magnetic albumin nanoparticles containing adriamycin in normal liver in rats[J], Chinese Journal of Modem Medicine, 2001; 11(3):4-7
15．刘利萍，吴泽志，李苹，等．天然高分子磁微球作为靶向制剂的研究进展[J]．药物生物技术，2004，11(1)：68-70
16．信涛，赵玉莹，徐玉清等．5可霉素白蛋白磁性纳米颗粒栓塞治疗大鼠原发性肝癌的实验研究．中国肿瘤临床，2007，34(24)：1422-1427
17. Zhu HG, Ji J,Shen JC,et al.Surface engineering of poly (DL-lactide) via electrostatic self-assembly of extracellular matrix-like molecules Biomacromolecules,2003, 4(2): 378-386
18. Thackray AC,Sammons RL, Macaskie LE,et al.Bacterial biosynthesis of a calcium phosphate bone-substitute material.J Mater Sci Mater Med 2004,15(4):403-406
19. Arias JL, Mayor MB, Pou J, et aI.Micro- and nano-testing of calcium phosphate coating produced by pulsed laser deposition.Biomaterials 2003:24(20):3403-3408
20. Hong Y, Gao CY, Shen JC,et al.Collagen-coated polylactide microspheres as chondrocyte microcarriers. Biomaterials, 2005,26(32):6305-6313
21. Zhang SG.Fabrication of novel biomaterials through molecular self-assembly.Nat Biotechnol,2003,21(10):1171-1178
22. Freitas RA Jr. Exploratory design in medical nan0techno10gy: a mechanical artificial red cell[J]. Cells Blood Substit Immobil Biotechnol, 1998, 26(4): 411 -430
23．王国清，钟季康 王保华．纳米技术及其在生物医学中的应用[J]．生物医学工程与临床，2002，6(2)：109-112
24．王 兰．纳米在临床诊断及治疗研究中的进展[J]．中国医师杂志，2002，4(3)：225-226
25. Kasili PM, Vo-Dinh T. Optical nanobiosensor for monitoring an apoptotic signaling process in a single living cell following photo dynamic therapy. J Nanosci Nanotechnol. 2005,5(12):2057-2062
26. Cullum BM, Vo-Dinh T. The development of optical nanosensors for biological measurements. Trends Biotechnol. 2000, 18(9):388-393
27. Zhang YB, Kanungo M, Ho AJ, et,al. Functionalized carbon nanotubes for detecting viral proteins. Nano Lett. 2007,7(10):3086-3091.