Fe(3)O(4)-based PLGA nanoparticles as MR contrast agents for the detection of thrombosis.
Fe(3)O(4)-based PLGA nanoparticles as MR contrast agents for the detection of thrombosis.
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DOI：
10.2147/ijn.s123228
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发表时间：
2017
影响因子：
8
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Liu J;Xu J;Zhou J;Zhang Y;Guo D;Wang Z
血栓性疾病是对人类健康的一大威胁，早期发现尤为重要。磁共振(MR)分子成像为早期疾病诊断提供了无创成像的可能性。在这项研究中，我们开发了基于Fe3O4的聚乳酸-乙醇酸共聚(PLGA)纳米颗粒(NPs)，表面修饰了一个环状Arg-Gly-Asp(CRGD)多肽，作为检测血栓形成的MR造影剂。对纳米粒的理化性质、生物毒性、靶向血栓的能力和生物分布进行了研究。成功构建了Fe3O4-PLGA-cRGD纳米粒，血液学和病理学检测表明该纳米粒无体内毒性。在FeCl3诱导的大鼠腹主动脉血栓形成模型中，NPs容易和选择性地聚集在血栓表面和血管内皮细胞下。在体内实验中，NPs的生物分布表明，NPs可能被肝和脾中的网状内皮系统的巨噬细胞所内化。T2信号在注射后10min在壁血栓处逐渐降低，然后逐渐升高至50min。这些结果表明，纳米粒子适合于高剪应力条件下血栓形成的在体分子成像，是一种非常有前途的敏感和特异的血栓检测磁共振对比剂。
Thrombotic disease is a great threat to human health, and early detection is particularly important. Magnetic resonance (MR) molecular imaging provides noninvasive imaging with the potential for early disease diagnosis. In this study, we developed Fe3O4-based poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface-modified with a cyclic Arg-Gly-Asp (cRGD) peptide as an MR contrast agent for the detection of thrombosis. The physical and chemical characteristics, biological toxicity, ability to target thrombi, and biodistribution of the NPs were studied. The Fe3O4-PLGA-cRGD NPs were constructed successfully, and hematologic and pathologic assays indicated no in vivo toxicity of the NPs. In a rat model of FeCl3-induced abdominal aorta thrombosis, the NPs readily and selectively accumulated on the surface of the thrombosis and under vascular endothelial cells ex vivo and in vivo. In the in vivo experiment, the biodistribution of the NPs suggested that the NPs might be internalized by the macrophages of the reticuloendothelial system in the liver and the spleen. The T2 signal decreased at the mural thrombus 10 min after injection and then gradually increased until 50 min. These results suggest that the NPs are suitable for in vivo molecular imaging of thrombosis under high shear stress conditions and represent a very promising MR contrast agent for sensitive and specific detection of thrombosis.