放射引导多肽靶向结合肿瘤的实验研究
发布时间：2018-08-28 13:03
【摘要】：目的：研究重组肽HVGGSSV特异性靶向结合放射损伤肿瘤的能力，探讨HVGGSSV在体内的分布情况，，为肿瘤分子靶向治疗提供一个新思路。 方法：用游离荧光染料Cy7-NHSester标记多肽HVGGSSV，合成Cy7-HVGGSSV复合物。以双后肢皮下接种人鼻咽癌细胞移植瘤的裸鼠作为实验模型,研究荧光多肽(Cy7-HVGGSSV)与放射损伤的肿瘤组织特异结合的靶向性。实验小鼠右后肢肿瘤给于6MV-X线3Gy放射处理，左后肢处肿瘤不接受放射线照射，随机分为对照和实验组，每组5只裸鼠，放射后4小时从尾静脉分别注射100ul游离Cy7-NHSester溶液和Cy7-HVGGSSV溶液。应用小动物活体成像系统检测实验小鼠在注射药物后不同时间点（1h，2h，15h，24h，48h）体内荧光分布,并比较双后肢肿瘤处的荧光量。48h后处死实验组小鼠，取出心、肺、肝、肾、肿瘤，观察各脏器及肿瘤的荧光量分布。通过小动物活体成像系统的软件处理平台在荧光分布图上勾画感兴趣的区域(ROI)并测量其荧光量子，通过比较感兴趣区域的总荧光量子判断目标区域的荧光分布强弱。 结果:1.在15h、24h观察点，实验组（Cy7-HVGGSSV组）小鼠右后肢肿瘤较左后肢肿瘤荧光分布分别高4.04×107±2.66×107phontos/s/cm2、5.63×107±2.42×107phontos/s/cm2，p＜0.05。2.在1h、2h、15h、24h、48h等观察点，实验组(Cy7-HVGGSSV组)较对照组(Cy7组)小鼠右后肢肿瘤区域的荧光量子高1.81×108±1.58×107phontos/s/cm2、1.28×108±3.49×107phontos/s/cm2、5.28×108±2.93×107phontos/s/cm2、6.0×108±2.69×107phontos/s/cm2、1.38×108±1.33×107phontos/s/cm2,p＜0.05。3.对照组小鼠的荧光分布无特异性，双后肢肿瘤荧光量子无明显差别。4.在注射后48小时，实验组小鼠体内脏器的荧光分布显示小鼠肝脏、肾脏具有较高的荧光量分布，而心脏、肺脏及肿瘤区域荧光分布较低。 结论：1.HVGGSSV可以特异性结合放射损伤的肿瘤组织，可以考虑作为放射引导药物靶向运输的载体；2.HVGGSSV可能通过肝脏及肾脏代谢。
[Abstract]:Objective: to study the ability of specific targeting of recombinant peptide HVGGSSV combined with radiation damage tumor, and to investigate the distribution of HVGGSSV in vivo, and to provide a new idea for tumor molecular targeted therapy. Methods: the free fluorescent dye Cy7-NHSester labeled polypeptide HVGGSSV, was used to synthesize Cy7-HVGGSSV complex. The specific binding of fluorescent polypeptide (Cy7-HVGGSSV) to radiation injured tumor was studied in nude mice inoculated subcutaneously with human nasopharyngeal carcinoma (NPC) cells in both hind limbs. The tumor of the right hind limb of the experimental mice was treated with 6MV-X line 3Gy radiation. The tumor of the left hind limb was not irradiated by radiation. The mice were randomly divided into control group and experimental group. Five nude mice in each group were injected 100ul free Cy7-NHSester solution and Cy7-HVGGSSV solution from caudal vein 4 hours after irradiation. The fluorescence distribution of experimental mice at different time points (1 h ~ 2 h ~ 15 h ~ 24 h ~ 48 h after injection) was detected by small animal imaging system in vivo. The mice in the experimental group were killed after the tumor of both hind limbs. The heart, lung, liver, kidney and tumor were taken out. The fluorescence distribution of various organs and tumors was observed. Using the software processing platform of small animal living imaging system, the (ROI) of the region of interest is drawn on the fluorescence distribution map and the fluorescence quantum of the region of interest is measured, and the intensity of the fluorescence distribution of the target region is judged by comparing the total fluorescence quantum of the region of interest. The result is 1: 1. The fluorescence distribution of tumor in the right hind limb of the experimental group (Cy7-HVGGSSV group) was 4.04 脳 107 卤2.66 脳 10 ~ 7phontosr / s / cm _ 2 5.63 脳 10 ~ 7 卤2.42 脳 10 ~ 7phontosr / s 路cm ~ (-2) P < 0.05.2, respectively, at the observation point of 15 h or 24 h. The fluorescence quantum in the tumor region of the right hind limb of the experimental group (Cy7-HVGGSSV group) was 1.81 脳 10 8 卤1.58 脳 10 7phontosr / s / cm 2: 1.28 脳 10 8 卤3.49 脳 10 7 phontosr / s / cm = 1.28 脳 10 8 卤3.49 脳 10 7 phonons / s / cm = 1.28 脳 10 7 / s / cm = 2.93 脳 10 7 phonos / s / cm = 2. 0 脳 10 8 卤2. 69 脳 10 7 phonons / s / cm 路cm ~ (-2) P < 0. 05. 3 脳 10 ~ 8 卤1. 33 脳 10 ~ 7 / P / cm ~ (2) P < 0. 05.33 脳 10 ~ 7 / s / cm ~ (-1) P < 0.05.3 脳 10 ~ (7) / s / cm ~ (-1). The fluorescence distribution of mice in the control group was not specific, and the fluorescence quantum of tumor in both hind limbs was not significantly different. 4. At 48 hours after injection, the fluorescence distribution of the viscera in the experimental group showed that the liver and kidney of the experimental group had a higher fluorescence distribution, but the fluorescence distribution in the heart, lung and tumor areas was lower than that in the control group. Conclusion: 1. HVGGSSV can specifically bind to tumor tissue injured by radiation, and it can be considered as a carrier of radiation-guided drug targeting transport. 2. HVGGSSV may be metabolized through liver and kidney.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R730.55
本文编号：2209474
[Abstract]:Objective: to study the ability of specific targeting of recombinant peptide HVGGSSV combined with radiation damage tumor, and to investigate the distribution of HVGGSSV in vivo, and to provide a new idea for tumor molecular targeted therapy. Methods: the free fluorescent dye Cy7-NHSester labeled polypeptide HVGGSSV, was used to synthesize Cy7-HVGGSSV complex. The specific binding of fluorescent polypeptide (Cy7-HVGGSSV) to radiation injured tumor was studied in nude mice inoculated subcutaneously with human nasopharyngeal carcinoma (NPC) cells in both hind limbs. The tumor of the right hind limb of the experimental mice was treated with 6MV-X line 3Gy radiation. The tumor of the left hind limb was not irradiated by radiation. The mice were randomly divided into control group and experimental group. Five nude mice in each group were injected 100ul free Cy7-NHSester solution and Cy7-HVGGSSV solution from caudal vein 4 hours after irradiation. The fluorescence distribution of experimental mice at different time points (1 h ~ 2 h ~ 15 h ~ 24 h ~ 48 h after injection) was detected by small animal imaging system in vivo. The mice in the experimental group were killed after the tumor of both hind limbs. The heart, lung, liver, kidney and tumor were taken out. The fluorescence distribution of various organs and tumors was observed. Using the software processing platform of small animal living imaging system, the (ROI) of the region of interest is drawn on the fluorescence distribution map and the fluorescence quantum of the region of interest is measured, and the intensity of the fluorescence distribution of the target region is judged by comparing the total fluorescence quantum of the region of interest. The result is 1: 1. The fluorescence distribution of tumor in the right hind limb of the experimental group (Cy7-HVGGSSV group) was 4.04 脳 107 卤2.66 脳 10 ~ 7phontosr / s / cm _ 2 5.63 脳 10 ~ 7 卤2.42 脳 10 ~ 7phontosr / s 路cm ~ (-2) P < 0.05.2, respectively, at the observation point of 15 h or 24 h. The fluorescence quantum in the tumor region of the right hind limb of the experimental group (Cy7-HVGGSSV group) was 1.81 脳 10 8 卤1.58 脳 10 7phontosr / s / cm 2: 1.28 脳 10 8 卤3.49 脳 10 7 phontosr / s / cm = 1.28 脳 10 8 卤3.49 脳 10 7 phonons / s / cm = 1.28 脳 10 7 / s / cm = 2.93 脳 10 7 phonos / s / cm = 2. 0 脳 10 8 卤2. 69 脳 10 7 phonons / s / cm 路cm ~ (-2) P < 0. 05. 3 脳 10 ~ 8 卤1. 33 脳 10 ~ 7 / P / cm ~ (2) P < 0. 05.33 脳 10 ~ 7 / s / cm ~ (-1) P < 0.05.3 脳 10 ~ (7) / s / cm ~ (-1). The fluorescence distribution of mice in the control group was not specific, and the fluorescence quantum of tumor in both hind limbs was not significantly different. 4. At 48 hours after injection, the fluorescence distribution of the viscera in the experimental group showed that the liver and kidney of the experimental group had a higher fluorescence distribution, but the fluorescence distribution in the heart, lung and tumor areas was lower than that in the control group. Conclusion: 1. HVGGSSV can specifically bind to tumor tissue injured by radiation, and it can be considered as a carrier of radiation-guided drug targeting transport. 2. HVGGSSV may be metabolized through liver and kidney.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R730.55
【参考文献】
相关期刊论文 前2条
1 侯清玉;杨秀萍;;肿瘤免疫逃逸的研究进展[J];中华肿瘤防治杂志;2010年03期
2 林少俊;宗井凤;廖希一;韩露;黄朝斌;潘建基;;西妥昔单抗联合放化疗治疗进展期鼻咽癌的临床研究[J];中国癌症杂志;2009年02期
本文编号：2209474
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