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放射引导的多肽特异性传输在肝癌放化疗模型中的应用

作者：吴君心 1 贺俊彦 1 乐雨银 2 苏颖 1 李金銮 1

单位：1.福建医科大学教学医院福建省肿瘤医院放射治疗科福建省肿瘤转化医学重点实验室福州 350000 2.福建省福州肺科医院肿瘤内科福州 350000

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出版年,卷(期):页码：2015,7(4):54-58

摘要：

摘要：目的本课题拟通过重组HVGGSSV多肽，研究其特异性结合放射损伤肿瘤细胞的特性，并观察
其体内分布及代谢情况，为肝癌特异性靶向治疗提供新方法。方法采用荧光染料Cy7-NHS ester标记
HVGGSSV，合成Cy7-HVGGSSV。建立人肝癌裸鼠双后肢种植瘤模型，所有小鼠首先经顺铂（DDP）
处理，然后小鼠右后肢肿瘤放射处理3Gy，左后肢处肿瘤不接受放射处理，将其随机分为对照和实验
组，每组5只小鼠，放射后4小时，实验组和对照组分别经尾静脉注射Cy7-HVGGSSV和Cy7-NHS ester。
通过小动物活体成像系统检测并观察小鼠体内不同时间点的荧光分布情况。结果实验组右后肢肿瘤
荧光强度在给药后1小时、2小时、15小时、24小时、48小时分别比左后肢肿瘤高（5.82 ± 1.24）× 10 7
photons/(s·cm 2 )、（8.99 ± 1.27）× 10 7 photons/(s·cm 2 )、（4.04 ± 2.30）× 10 7 photons/(s·cm 2 )、（6.52 ±
3.93）× 10 7 photons/(s·cm 2 )、（9.33 ± 1.74）× 10 7 photons/(s·cm 2 )。实验组较对照组右后肢肿瘤荧光强
度分别提高（18.4 ± 1.33）× 10 7 photons/(s·cm 2 )、（17.1 ± 1.64）× 10 7 photons/(s·cm 2 )、（55.8 ± 2.66）×
10 7 photons/(s·cm 2 )、（68.9 ± 3.97）× 10 7 photons/(s·cm 2 )、（16.3 ± 1.67）× 10 7 photons/(s·cm 2 )。对照组荧
光分布无特异性。48 h后，实验组小鼠的肝脏及肾脏具有较高荧光量分布。结论 HVGGSSV可以特异性
结合放射损伤的肝癌移植瘤，其主要通过肝脏及肾脏代谢，有可能为放射引导的药物提供靶向运输载体。

Abstract: Objective To investigate the characteristics of peptide HVGGSSV, which specifically binds to
irradiated tumors, and its biological distribution in vivo in order to provide a new way for targeted cancer
therapy of hepatic carcinoma. Methods HVGGSSV peptide was conjugated to Cy7-NHS ester for near-
infrared fluorescence imaging. The nude mice models of hepatic carcinoma which implanted in both hind
limbs were established, and all of them were injected through intraperitoneal with DDP before treated
with radiation. Only the tumor on the right side of each mouse received a radiation dose of 3 Gy, while the
tumor on the left side received no radiation. All mice were divided into two groups with 5 mice each. Four
hours later, experimental group and control group were injected with Cy7-HVGGSSV and Cy7-NHS ester,
respectively. All mice were anesthetized and quantified with the Caliper Luminal IVIS Ⅱ small animal
imaging system at different time after injection. Results Near-infrared images were acquired at 1, 2, 15,
24, and 48 hours post-injection by using in vivo NIR imaging. For the experimental group, the fluorescence
intensity of the tumor in the right hind limb was (5.82 ± 1.24) × 10 7 photons/(s·cm 2 ), (8.99 ± 1.27) × 10 7
photons/(s·cm 2 ), (4.04 ± 2.30) × 10 7 photons/(s·cm 2 ), (6.52 ± 3.93) × 10 7 photons/(s·cm 2 ), (9.33 ± 1.74) × 10 7
photons/(s·cm 2 ), which were higher than those in the left hind limb, respectively. The results of the experimental group
in the right hind limb was (18.4 ± 1.33) × 10 7 photons/(s·cm 2 ), (17.1 ± 1.64) × 10 7 photons/(s·cm 2 ), (55.8 ± 2.66) × 10 7
photons/(s·cm 2 ), (68.9 ± 3.97) × 10 7 photons/(s·cm 2 ), (16.3 ± 1.67) × 10 7 photons/(s·cm 2 ) , which were higher than those
in the control group, respectively. There was still high fluorescence distribution in the liver and kidney at 48 hours post-
injection. Conclusion HVGGSSV peptide could specifically bind to irradiated hepatic tumors, and mainly metabolized in
the kidney and liver, it might provide a targeting transport agent for radiation-guided drugs

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