| 乐雨银,黄磊娟,贺俊彦.放射特异性重组肽HVGGSSV在胰腺癌移植瘤模型中的研究[J].肿瘤学杂志,2017,23(6):502-507. |
| 放射特异性重组肽HVGGSSV在胰腺癌移植瘤模型中的研究 |
| Recombinant Peptide HVGGSSV Targeting to Irradiated Human Pancreatic Carcinoma in Nude Mice |
| 投稿时间：2016-10-08 |
| DOI：10.11735/j.issn.1671-170X.2017.06.B009 |
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| 中文关键词: 重组肽HVGGSSV 放射特异性引导 药物靶向 胰腺肿瘤 |
| 英文关键词:peptide HVGGSSV radiation-guided peptide delivery tumor targeting therapy pancreatic carcinoma xenograft model |
| 基金项目:福建省自然科学基金 (2012J01331; 2016J01437) |
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| 中文摘要: |
| 摘 要：［目的］ 探讨放射特异性重组肽HVGGSSV靶向结合胰腺癌移植瘤的生物功能。［方法］ 合成可以识别肿瘤组织放射损伤的重组肽HVGGSSV，利用游离荧光染料Cy7-NHS ester 标记，制备具有肿瘤特异性的荧光靶向载体复合物Cy7-HVGGSSV颗粒。建立人胰腺癌裸鼠双后肢移植瘤模型，右后肢接受单次放射4Gy，随机分组，放射后5h，实验组接受Cy7-HVGGSSV处理，对照组接受Cy7-NHS ester处理。应用小动物活体成像系统观察负瘤小鼠双后肢肿瘤区域的荧光分布情况。［结果］ 小动物活体成像系统显示给药后1h、6h、12h、24h、48h，实验组右后肢肿瘤荧光强度分别比左后肢肿瘤分别提高6.440×107±1.803×107phontos/s/cm2（t=-8.958，P＜0.001）、8.044×107±1.001×107phontos/s/cm2（t=-8.802，P＜0.001）、3.879×108±6.26×107 phontos/s/cm2（t=-14.082，P＜0.001）、5.732×108±4.762×107phontos/s/cm2（t=-24.375，P＜0.001）、7.836×107±3.50×106 phontos/s/cm2（t=-4.831，P=0.001）。实验组较对照组右后肢肿瘤荧光强度在各时间点分别提高1.918×108±3.011×107（t=-11.554，P＜0.001）phontos/s/cm2、1.301×108 ±7.884×107phontos/s/cm2（t=-3.954，P=0.004）、5.486×108±7.242×107phontos/s/cm2（t=-18.001，P＜0.001）、6.149×108±5.398×107phontos/s/cm2（t=-24.454，P＜0.001）、1.473×108±3.050×107（t=-9.681，P＜0.001）phontos/s/cm2。实验组较对照组左后肢肿瘤荧光强度各时间点分别提高1.287×108±2.702×107（t=-8.767，P＜0.001）phontos/s/cm2、5.690×107±7.511×107phontos/s/cm2（t=-1.627，P=0.142）、1.612×108±2.619×107phontos/s/cm2（t=-7.916，P＜0.001）、4.260×107±2.398×107phontos/s/cm2（t=-3.966，P=0.004）、6.913×107±1.130×107（t=-12.35，P＜0.001）phontos/s/cm2。［结论］ 初步研究显示重组肽HVGGSSV可特异性结合放射损伤的胰腺癌移植瘤，为胰腺癌药物靶向治疗提供新思路。 |
| 英文摘要: |
| Abstract：［Objective］ To evaluate the application of recombinant peptide HVGGSSV targeting to irradiated human pancreatic carcinoma in nude mice. ［Methods］ The HVGGSSV peptide was labeled with Cy7-NHS ester for fluorescence imaging. Human SW1990 pancreatic carcinoma was implanted in nude mice on both hind limbs；the tumor on right side received a 4Gy radiation，while the left side was spared from radiation. The mice were randomized into two groups with 5 in each；5h after radiation fluorescence-conjugated Cy7-HVGGSSV was injected in experimental group and Cy7-NHS was injected in control group. All mice were anesthetized and examined with the Caliper Luminal IVIS II small animal imaging system at 1h，6h，12h，24h，48h after injection，respectively. ［Results］The near-infrared images were acquired at 1h，6h，12h，24h and 48h after injection，images of the experimental group showed maximum radiance，whereas untreated(0Gy) control tumors showed lower levels of radiance across all treatment groups. Irradiated tumors treated with Cy7 labeled-HVGGSSV showed 6.440×107±1.803×107phontos/s/cm2（t=-8.958，P＜0.001），8.044×107±1.001×107phontos/s/cm2（t=-8.802，P＜0.001），3.879×108±6.26×107phontos/s/cm2（t=-14.082，P＜0.001），5.732×108±4.762×107phontos/s/cm2（t=-24.375，P＜0.001）and 7.836×107±3.50×106 phontos/s/cm2（t=-4.831，P＜0.001）higher radiance compared to untreated tumors at 1，6， 12，24 and 48 h，respectively. For the experimental group，the fluorescence intensites of the tumor in the right hind limb were 1.918×108±3.011×107（t=-11.554，P＜0.001）phontos/s/cm 2，1.301×108 ±7.884×107phontos/s/cm2（t=-3.954，P=0.004），5.486×108±7.242×107 phontos/s/cm2（t=-18.001，P＜0.001），6.149×108±5.398×107 phontos/s/cm2（t=-24.454，P＜0.001） and 1.473×108±3.050×107（t=-9.681，P＜0.001）phontos/s/cm2 higher than those in group Cy7 alone at all time points，respectively. And the fluorescence intensities of the tumor in the left hind limb were 1.287×108±2.702×107（t=-8.767，P＜0.001）phontos/s/cm2，5.690×107±7.511×107 phontos/s/cm2（t=-1.627，P=0.142），1.612×108±2.619×107 phontos/s/cm2（t=-7.916，P＜0.001），4.260×107±2.398×107phontos/s/cm2（t=-3.966，P=0.004），6.913×107±1.130×107（t=-12.35，P＜0.001）phontos/s/cm2 higher than those in the control group.［Conclusion］ The study demonstrates the remarkable capability of the HVGGSSV peptide of selectively binding to irradiated tumors，which might provide a new way for radiation-guided delivery of anticancer drugs. |
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