大鼠C6胶质瘤MR显像及靶向治疗的多功能纳米药物载体研究

发布时间：2018-03-29 04:04

本文选题：纳米粒子　切入点：药物载体　出处：《安徽医科大学》2014年硕士论文

【摘要】：研究背景及目的近年来随着抗肿瘤药物的迅速发展，化疗在胶质瘤治疗中的地位越来越重要。阿霉素（doxorubicin，DOX）是临床上最常用的抗肿瘤药物之一，它抗肿瘤活性强，但其对正常组织和器官的毒副作用大，这严重限制了其在肿瘤治疗中的应用。因此构建一种可以携带DOX导向性药物输送载体对肿瘤治疗的研究具有非常重要的意义。本论文选用叶酸（folic acid，FA）修饰的载DOX Mn纳米粒子体系，不仅能使DOX在胶质瘤病灶部位富集，还可以通过MRI监测药物在体内的分布。本实验利用Mn纳米粒子对大鼠C6胶质瘤脑内及皮下肿瘤模型进行3T磁共振成像，并对它们的成像特征进行研究，可以更真实的观测肿瘤的生长规律；利用磁共振活体示踪法并且结合HE染色证实FA修饰的载DOX Mn纳米粒子体系对大鼠C6胶质瘤的治疗效果。材料和方法 10只，SD大鼠，清洁级，，雄性，250-280g；收集对数生长期的鼠C6胶质瘤细胞，建立大鼠C6脑胶质瘤模型，接种7d后行MR扫描，然后通过鼠尾静脉注射0.5ml Mn纳米粒子，分别于注射后5min、24h再次行MR扫描，扫描结束后取出脑内肿瘤组织行HE染色。10只，SD大鼠，清洁级，雄性，150-180g，收集对数生长期大鼠C6胶质瘤细胞，建立大鼠C6皮下胶质瘤模型，接种第7d先行MR平扫，再通过鼠尾静脉注射0.5ml Mn纳米粒子，分别于注射后5min、1h再次行MR扫描，扫描结束后剥离皮下肿瘤，行HE染色。建立大鼠C6皮下胶质瘤模型20只，随机分为四组，于接种后第10、11、12、14d分别经鼠尾静脉注射0.5ml FA修饰的载DOX Mn纳米粒子(FA-Mn-DOX)、生理盐水、DOX、载DOX Mn纳米粒子（Mn-DOX），接种后的10-18d荷瘤鼠每天行MR扫描，MR扫描采集的图像传至ADW4.4工作站，在肿瘤最大层面测量肿瘤的最长径（L）、最宽径（W），计算肿瘤的体积；随后将肿瘤完整剥离下来，石蜡包埋后行HE染色。结果成功建立了大鼠C6脑胶质瘤模型、大鼠C6皮下胶质瘤模型，并用Mn纳米粒子对肿瘤实现MR成像， MRI检测更准确反映脑内、皮下C6胶质瘤呈指数的生长规律。自第1次给药后至第18d各时间段，与对照组相比，实验各组肿瘤体积均有不同程度的下降，差异有统计学意义（P0.05）；HE染色见FA-Mn-DOX组、DOX组、Mn-DOX组肿瘤细胞发生了一系列不可逆损害变化，其中以FA-Mn-DOX组最为显著。结论应用Mn纳米粒子对大鼠C6胶质瘤活体示踪MR成像，可以反映肿瘤的生物学特性，适用于肿瘤生长规律的观察和实验性治疗效果的评价；FA-Mn-DOX系一种多功能纳米药物载体，可作为磁共振靶向造影剂的同时，还具有双靶向治疗的作用，对大鼠C6皮下胶质瘤具有诊断和治疗的双重作用。
[Abstract]:Research background and purpose. In recent years, with the rapid development of antitumor drugs, chemotherapy is becoming more and more important in the treatment of glioma. Doxorubicin doxorubicin doxorubin dox is one of the most commonly used antitumor drugs in clinic, and it has strong antitumor activity. But its toxic side effects on normal tissues and organs are great. Therefore, it is very important to construct a carrier carrying DOX oriented drug delivery vector for the study of tumor therapy. In this paper, folic acid folic acid FA-FA-modified DOX mn nanoparticles system was selected. It can not only enrich DOX in glioma foci, but also monitor the distribution of drugs in vivo by MRI. In this experiment, 3T magnetic resonance imaging was performed on C6 glioma brain and subcutaneous tumor models using mn nanoparticles, and their imaging characteristics were studied, so that the growth law of C6 glioma could be observed more truthfully. The effect of FA modified DOX mn nanoparticles system on C6 glioma in rats was confirmed by in vivo magnetic resonance tracer method and HE staining. Materials and methods. Ten SD rats, clean grade, male, 250-280 g.The C6 glioma cells in logarithmic growth phase were collected, and the rat C6 glioma model was established. After 7 days of inoculation, Mr scanning was performed, and then 0.5ml mn nanoparticles were injected into the tail vein of rats. Mr scanning was performed again at 5 min and 24 h after injection. After the scan, 10 SD rats were stained with HE. The C6 glioma model was established by collecting C6 glioma cells in logarithmic phase of C6 glioma rats. On the 7th day of inoculation, Mr plain scan was performed first, then 0.5ml mn nanoparticles were injected into the tail vein of mice. Mr scanning was performed again at 5 min and 1 hour after injection. The subcutaneous tumor was stripped off and stained with HE after the scanning. Twenty rat C6 subcutaneous glioma models were established. Four groups were randomly divided into four groups. On the 10th day after inoculation, the DOX mn nanoparticles modified by 0.5ml FA were injected into the tail vein of mice at 14 days after inoculation. The DOX mn nanoparticles (FA-Mn-DOXX), normal saline dox and DOX mn nano-particles were injected into the tail vein of mice respectively. The images collected by Mr scanning were transmitted to ADW4.4 workstation every day on 10-18 days after inoculation. The maximum diameter of the tumor was measured at the maximum level of the tumor, and the volume of the tumor was calculated. Then, the tumor was stripped off completely and stained with HE after paraffin embedded. Results. The rat C6 glioma model and rat C6 subcutaneous glioma model were successfully established. Mr imaging of the tumor was realized with mn nanoparticles, and the brain was more accurately reflected by MRI detection. The growth pattern of subcutaneous C6 glioma was exponential. From the first administration to the 18th day, compared with the control group, the tumor volume of each experimental group decreased in varying degrees. The difference was statistically significant (P 0.05) and HE staining showed that there were a series of irreversible changes in tumor cells in FA-Mn-DOX group, especially in FA-Mn-DOX group. Conclusion. The in vivo tracer Mr imaging of rat C6 glioma with mn nanoparticles can reflect the biological characteristics of the tumor. It is suitable for the observation of tumor growth and the evaluation of experimental therapeutic effect. FA-Mn-DOX is a multifunctional nano-drug carrier. It can be used as Mr target contrast agent and can also be used as a double target therapy for C6 subcutaneous glioma in rats, and it can be used in the diagnosis and treatment of C6 subcutaneous glioma.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R739.41;R445.2

【参考文献】