Tumor angiogenesis targeting and imaging using gold nanoparticle probe with directly conjugated cyclic NGR

Wu Minghao; Zhang Yanyan; Zhang Ying; Wu Mingjie; Wu Menglin; Wu Hongyi; Cao Lin; Li Liang; Li Xue; Zhang Xuening

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Tumor angiogenesis targeting and imaging using gold nanoparticle probe with directly conjugated cyclic NGR

机译：肿瘤血管生成使用金纳米粒子探针用直接共轭循环NGR靶向和成像

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Angiogenesis is a vital process for the growth and metastasis of malignant tumor. Visualization of tumor angiogenesis is thus of great importance in the evaluation of biologic aggressiveness as well as monitoring of the response to anti-angiogenic therapy. Herein, we developed a probe based on gold nanoparticles (GNPs) directly surface-functionalized with a tumor-homing cyclized asparagine-glycine-arginine peptide (SH-cNGR) and carboxylpoly(ethylene glycol) thiol (SH-PEG-COOH) via Au-S bonds. The obtained GNPs-PEG@cNGR probe was used to target the aminopeptidase-N (APN/CD13), which overexpressed in the endothelium of tumor angiogenesis. The CD13 binding affinities of the peptides were assessed by a receptor binding assay based on HUVEC and HepG2 cell (e.g. fluorescence imaging and X-ray computed tomography (CT)). The tumor targeting efficacy and the distribution of the GNPs-PEG@cNGR in vivo were further evaluated in a subcutaneous 4T1 xenograft model by CT imaging and immunohistochemistry study. These results showed that the GNPs-PEG@cNGR rapidly and specifically bound to the tumor vasculature after intravenous injection. Quantitative studies demonstrated that GNPs-PEG@cNGR showed significantly higher and faster tumor uptake after intravenous injection compared to unlabeled GNPs-PEG. Moreover, the distribution of tumor enhancement was consistent with the spatial distribution of angiogenic blood. These results suggest that the designed GNPs-PEG@cNGR probe may serve, in principle, as a promising CT contrast agent for targeted angiogenesis imaging and quantitative analysis.

机译：血管生成是恶性肿瘤生长和转移的重要过程。因此，肿瘤血管生成的可视化在对生物学侵略性的评估以及对抗血管生成治疗的反应的监测中具有重要意义。在此，我们开发了基于金纳米颗粒（GNP）的探针，直接用肿瘤归巢环状的天冬酰胺 - 精氨酸肽（SH-CNGR）和羧基聚（乙二醇）硫醇（SH-PEG-COOH）通过AU -s债券。获得的GNPS-PEG @ CNGR探针用于靶向氨基肽酶-N（APN / CD13），其在肿瘤血管生成内皮中过表达。通过基于HUVEC和HepG2细胞的受体结合测定评估肽的CD13结合亲和力（例如荧光成像和X射线计算断层扫描（CT））。通过CT成像和免疫组织化学研究，进一步评估体内肿瘤靶向疗效和GNPS-PEG @ CNGR的分布。这些结果表明，静脉注射后，GNPS-PEG @ CNGR快速，特异性地结合肿瘤脉管系统。定量研究表明，与未标记的GNPS-PEG相比，GNPS-PEG @ CNGR显示出静脉注射后的肿瘤摄取显着更高，肿瘤摄取更快。此外，肿瘤增强的分布与血管生成血液的空间分布一致。这些结果表明，设计的GNPS-PEG @ CNGR探针原则上可以作为有前途的CT造影剂，用于靶向血管生成成像和定量分析。

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来源
《RSC Advances》 |2018年第3期|共11页
作者
Wu Minghao; Zhang Yanyan; Zhang Ying; Wu Mingjie; Wu Menglin; Wu Hongyi; Cao Lin; Li Liang; Li Xue; Zhang Xuening;
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Tianjin Med Univ Hosp 2 Dept Med Imaging Tianjin 300211 Peoples R China;

Tianjin Med Univ Hosp 2 Dept Med Imaging Tianjin 300211 Peoples R China;

Tianjin Med Univ Hosp 2 Dept Med Imaging Tianjin 300211 Peoples R China;

Inst Natl Rech Sci Energie Mat &

Telecommun Varennes PQ J3X 1S2 Canada;

Tianjin Med Univ Hosp 2 Dept Med Imaging Tianjin 300211 Peoples R China;

Tianjin Med Univ Hosp 2 Dept Med Imaging Tianjin 300211 Peoples R China;

Tianjin Med Univ Hosp 2 Dept Med Imaging Tianjin 300211 Peoples R China;

Tianjin Med Univ Hosp 2 Dept Med Imaging Tianjin 300211 Peoples R China;

Tianjin Med Univ Hosp 2 Dept Med Imaging Tianjin 300211 Peoples R China;

Tianjin Med Univ Hosp 2 Dept Med Imaging Tianjin 300211 Peoples R China;

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正文语种 eng
中图分类化学;
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专利

1. Tumor angiogenesis targeting and imaging using gold nanoparticle probe with directly conjugated cyclic NGR [J] . Wu Minghao, Zhang Yanyan, Zhang Ying, RSC Advances . 2018,第3期

机译：肿瘤血管生成使用金纳米粒子探针用直接共轭循环NGR靶向和成像
2. Magnetic resonance imaging of tumor angiogenesis using dual-targeting RGD10-NGR9 ultrasmall superparamagnetic iron oxide nanoparticles [J] . Wu T., Ding X., Su B., Clinical & translational oncology : . 2018,第5期

机译：使用双靶向RGD10-NGR9超超顺磁性氧化铁纳米颗粒肿瘤血管生成的磁共振成像
3. ~(68)Ga-Chelation and comparative evaluation of N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]- ethylenediamine-N,N'-diacetic acid (HBED-CC) conjugated NGR and RGD peptides as tumor targeted molecular imaging probes [J] . Drishty Satpati, Rohit Sharma, Chandan Kumar, MedChemComm . 2017,第3期

机译：〜（68）N，N'-BIS-[2-羟基-5-（羧乙基）苄基] - 乙二胺-N，N'-乙二酸（HBED-CC）共轭NGR和RGD肽的GA - 螯合和对比评价作为肿瘤靶向分子成像探针
4. Two-Photon AIE Probe Conjugated Theranostic Nanoparticles for Tumor Bioimaging and pH-Sensitive Drug Delivery [C] . Boxuan Ma, Weihua Zhuang, Gaocan Li, Society for Biomaterials annual meeting and exposition . 2019

机译：两光子AIE探针缀合了治疗性纳米颗粒，用于肿瘤生物成像和pH敏感药物递送
5. Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors. [D] . Etame, Arnold B. 2012

机译：具有靶向人类脑肿瘤治疗潜力的金纳米颗粒的增强递送。
6. 68Ga-Chelation and comparative evaluation of NN′-bis-2-hydroxy-5-(carboxyethyl)benzylethylenediamine-NN′-diacetic acid (HBED-CC) conjugated NGR and RGD peptides as tumor targeted molecular imaging probes [O] . Drishty Satpati, Rohit Sharma, Chandan Kumar, 2017

机译：NN-双-2-羟基-5-（羧乙基）苄基乙二胺-NN-二乙酸（HBED-CC）共轭的NGR和RGD肽的68Ga螯合和比较评价作为肿瘤靶向分子成像探针
7. Integrin αvβ3–Targeted Dynamic Contrast–Enhanced Magnetic Resonance Imaging Using a Gadolinium-Loaded Polyethylene Gycol–Dendrimer–Cyclic RGD Conjugate to Evaluate Tumor Angiogenesis and to Assess Early Antiangiogenic Treatment Response in a Mouse Xenograft Tumor Model [O] . Wei-Tsung Chen, Tiffany Ting Fang Shih, Ran-Chou Chen, 2012

机译：整合素αvβ3靶向动态对比增强磁共振成像使用负载钆的聚乙烯Gycol-树枝状大分子 - 环状RGD缀合物评估肿瘤血管生成和评估小鼠异种移植肿瘤模型中的早期抗血管生成治疗反应

Tumor angiogenesis targeting and imaging using gold nanoparticle probe with directly conjugated cyclic NGR

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