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[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6.440×10~7±1.803×10~7phontos/s/cm~2(t=-8.958,P<0.001)、8.044×10~7±1.001×10~7phontos/s/cm~2(t=-8.802,P<0.001)、3.879×10~8±6.26×10~7phontos/s/cm~2(t=-14.082,P<0.001)、5.732×10~8±4.762×10~7phontos/s/cm~2(t=-24.375,P<0.001)、7.836×10~7±3.50×10~6phontos/s/cm~2(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1.918×10~8±3.011×10~7(t=-11.554,P<0.001)phontos/s/cm~2、1.301×10~8±7.884×10~7phontos/s/cm~2(t=-3.954,P=0.004)、5.486×10~8±7.242×10~7phontos/s/cm~2(t=-18.001,P<0.001)、6.149×10~8±5.398×10~7phontos/s/cm~2(t=-24.454,P<0.001)、1.473×10~8±3.050×10~7(t=-9.681,P<0.001)phontos/s/cm~2。实验组较对照组左后肢肿瘤荧光强度各时间点分别提高1.287×10~8±2.702×10~7(t=-8.767,P<0.001)phontos/s/cm~2、5.690×10~7±7.511×10~7phontos/s/cm~2(t=-1.627,P=0.142)、1.612×10~8±2.619×10~7phontos/s/cm~2(t=-7.916,P<0.001)、4.260×10~7±2.398×10~7phontos/s/cm~2(t=-3.966,P=0.004)、6.913×10~7±1.130×10~7(t=-12.35,P<0.001)phontos/s/cm~2。[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。
[Objective] To investigate the biological function of radiation-specific recombinant peptide HVGGSSV in targeting pancreatic cancer xenografts. [Method] Recombinant peptide HVGGSSV, which can recognize the radiation injury of tumor tissue, was synthesized and Cy7-HVGGSSV particles with tumor-specific fluorescent targeting vector were prepared by labeling with Cy7-NHS ester free fluorescent dye. A double-hind limb xenograft model of human pancreatic adenocarcinoma was established. The right hind limbs received a single irradiation of 4Gy and were randomly assigned to receive Cy7-HVGGSSV treatment 5h after irradiation. The control group received Cy7-NHS ester treatment. The live animal imaging system was used to observe the fluorescence distribution in the tumor area of the double hind limb in the negative tumor mice. [Results] The live animal imaging system showed that the fluorescence intensity of the right hindlimb tumor in the experimental group increased by 6.440 × 10 ~ 7 ± 1.803 × 10 ~ 7phontos / s / h than that of the left hindlimb respectively at 1h, 6h, 12h, 24h and 48h after the administration cm 2 (t = -8.958, P <0.001), 8.044 × 10 -7 ± 1.001 × 10 7phontos / s / cm 2 (t = -8.802, P <0.001) and 3.879 × 10 -8 ± 6.26 × (T = -14.082, P <0.001), 5.732 × 10 ~ 8 ± 4.762 × 10 ~ 7phontos / s / cm ~ 2 10 ~ 7 ± 3.50 × 10 ~ 6phontos / s / cm ~ 2 (t = -4.831, P = 0.001). Compared with the control group, the fluorescence intensity of the right hindlimb in experimental group increased by 1.918 × 10 ~ 8 ± 3.011 × 10 ~ 7 (t = -11.554, P <0.001) at each time point ± 7.884 × 10 ~ 7phontos / s / cm ~ 2 (t = -3.954, P = 0.004) and 5.486 × 10 ~ 8 ± 7.242 × 10 ~ 7phontos / s / cm ~ , 6.149 × 10 8 ± 5.398 × 10 7phontos / s / cm 2 (t = -24.454, P <0.001) and 1.473 × 10 -8 ± 3.050 × 10 -7 (t = -9.681, phontos / s / cm ~ 2. The fluorescence intensity of the left hindlimb in the experimental group increased by 1.287 × 10 ~ 8 ± 2.702 × 10 ~ 7 (t = -8.767, P <0.001) at each time point, and the phontos / s / cm ~ 2,5.690 × 10 ~ 7 ± 1.611 × 10 ~ 7 phontos / s / cm ~ 2 (t = -1.627, P = 0.142) 4.260 × 10 ~ 7 ± 2.398 × 10 ~ 7phontos / s / cm ~ 2 (t = -3.966, P = 0.004) and 6.913 × 10 ~ 7 ± 1.130 × 10 ~ 7 (t = -12.35, P <0.001) / s / cm ~ 2. [Conclusion] Preliminary studies have shown that the recombinant peptide HVGGSSV can specifically bind with radiation-injured pancreatic cancer xenografts and provide new ideas for the targeted therapy of pancreatic cancer.