| 刘 灿,李 媛,孙 锐,漆辉雄,刘东伯,仇树帅.靶向肿瘤新生血管的磁共振造影剂RGD-USPIO的制备及其体外成像研究[J].,2025,(1):146-153 |
| 靶向肿瘤新生血管的磁共振造影剂RGD-USPIO的制备及其体外成像研究 |
| Preparation and in vitro Imaging Study of Magnetic Resonance Contrast Agent RGD-USPIO Targeting Tumor Neovascularization |
| 投稿时间：2024-07-15 |
| DOI：10.13241/j.cnki.pmb.2025.01.021 |
| 中文关键词: MR分子成像 肿瘤 纳米造影剂 整合素αvβ3 氧化铁纳米颗粒 |
| 英文关键词: MR Molecular Imaging Tumor Nano-contrast agent Integrin αvβ3 Iron Oxide Nanoparticles |
| 基金项目:国家自然科学基金项目（82372918）；2021年度武汉市卫生健康委员会科研项目（WX21C28）；武汉市科技局2022年度知识创新专项基础研究项目（2020020801010559） |
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| 中文摘要: |
| 摘要 目的：本研究旨在制备一种针对肿瘤外周新生血管内皮αvβ3整合素的新型靶向纳米磁共振（MR）造影剂，并在体外环境中利用高场强MR对其成像特性进行深入探究。方法：通过碳二亚胺法，将小分子环肽精氨酸-甘氨酸-天冬氨酸（RGD）-苯丙氨酸-谷氨酸（cRGDfE）与超小型超顺磁性氧化铁纳米颗粒（USPIO）偶联，成功制备出RGD-USPIO纳米复合物造影剂。随后，我们利用透射电镜（TEM）对RGD-USPIO的物理特性进行了详细检测。为了验证其靶向性和特异性，我们选择了高表达αvβ3整合素的人脐静脉内皮细胞（HUVECS）作为研究对象，并通过铁染色技术检测了RGD-USPIO对αvβ3的靶向性和特异性。此外，我们还利用TEM观察了RGD-USPIO在细胞内的分布情况。最后，通过4.7T MR技术，我们检测了不同时间间隔内，HUVECS摄取USPIO和RGD-USPIO后MR的T2值的变化情况。结果：实验结果显示，RGD-USPIO具有较小的粒径和良好的分散度，能够特异性地与αvβ3整合素结合，展现出优异的靶向性。在HUVECS中，RGD-USPIO主要分布于细胞膜表面及胞浆内。与USPIO组相比，RGD-USPIO组在MR中T2信号强度（SI）显著下降，差异具有统计学意义（P＜0.05）。结论：本研究成功制备了一种具有靶向性和特异性的MR纳米造影剂-RGD-USPIO，该造影剂能够特异性地与HUVECS上高表达的整合素αvβ3相结合，并显著降低4.7T MR的T2值。这一研究为后续的体内实验提供了有力的实验依据，有望为肿瘤新生血管的精准诊断提供新的技术手段。 |
| 英文摘要: |
| ABSTRACT Objective: This study aimed to prepare a novel targeted nano-magnetic resonance (MR) contrast agent targetingαvβ3 integrin on the neovascular endothelium of tumors and to explore its imaging characteristics in depth using high-field MR in vitro. Methods: Through the carbodiimide method, the small molecule cyclic peptide arginine-glycine-aspartic acid (RGD)-phenylalanine-glutamic acid (cRGDfE) was successfully coupled with ultra-small superparamagnetic iron oxide nanoparticles (USPIO) to prepare the RGD-USPIO nanocomposite contrast agent. Subsequently, we used transmission electron microscopy(TEM) to examine the physical properties of RGD-USPIO in detail. To verify its targeting and specificity, we selected human umbilical vein endothelial cells (HUVECSs) with high expression ofαvβ3 integrin as the research object, and detected the targeting and specificity of RGD-USPIO toαvβ3 by iron staining technique. Additionally, we observed the intracellular distribution of RGD-USPIO using TEM. Finally, we examined the changes in MR T2 values at different time intervals after HUVECS uptake of USPIO and RGD-USPIO using 4.7T MR technology. Results: Experimental results showed that RGD-USPIO had a small particle size and good dispersibility, could specifically bind toαvβ3 integrin, and demonstrated excellent targeting. In HUVECSs, RGD-USPIO was mainly distributed on the cell membrane surface and in the cytoplasm. Compared with the USPIO group, the RGD-USPIO group showed a significant decrease in T2 signal intensity (SI) in MR, and the difference was statistically significant (P<0.05). Conclusion: This study successfully prepared a targeted and specific MR nano-contrast agent, RGD-USPIO, which can specifically bind to the highly expressed integrinαvβ3 on HUVECSs and significantly reduce the T2 value of 4.7T MR. This study provides a strong experimental basis for subsequent in vivo experiments and is expected to provide new technical means for precise diagnosis of tumor neovascularization. |
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