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Folate-PEG-superparamagnetic iron oxide nanoparticles for lung cancer imaging

机译：叶酸-PEG-超顺磁性氧化铁纳米颗粒用于肺癌成像

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摘要

While superparamagnetic iron oxide nanoparticles (SPIONs) have been widely used in biomedical applications, rapid blood clearance, instability and active targeting of the SPIONs limit their availability for clinical trials. This work was aimed at developing stable and lung cancer targeted SPIONs. For this purpose firstly folic acid (FA)-conjugated poly(ethylene glycol) (FA-PEG) was synthesized, and FA-PEG-SPIONs were subsequently prepared by the reaction of FA-PEG with aminosilane-immobilized SPIONs. FA-PEG-SPIONs were labeled with Cy5.5 for optical imaging. The intracellular uptake of FA-PEG-SPIONs-Cy5.5 was evaluated in KB cells and lung cancer model mice to confirm active targeting. The sizes of the FA-PEG-SPIONs were little changed after up to 8 weeks at 4 °C, suggestive of very stable particle sizes. The results of fluorescent flow cytometry and confocal laser scanning microscopy suggest that the intracellular uptake of FA-PEG-SPIONs-Cy5.5 was greatly inhibited by pre-treatment with free folic acid, indicative of receptor-mediated endocytosis. Stronger optical imaging was observed in the lung cancer model mice for FA-PEG-SPIONs-Cy5.5 than PEG-SPIONs-Cy5.5 6 and 24 h post-injection through the tail vein, due to receptor-mediated endocytosis.
机译：尽管超顺磁性氧化铁纳米粒子（SPIONs）已广泛用于生物医学应用，但SPIONs的快速血液清除，不稳定性和主动靶向性限制了其在临床试验中的可用性。这项工作旨在开发稳定的和靶向肺癌的SPIONs。为此，首先合成叶酸（FA）-共轭的聚乙二醇（FA-PEG），然后通过FA-PEG与氨基硅烷固定的SPIONs的反应制备FA-PEG-SPION。用Cy5.5标记FA-PEG-SPION用于光学成像。在KB细胞和肺癌模型小鼠中评估了FA-PEG-SPIONs-Cy5.5的细胞内摄取，以确认主动靶向。在4°C下放置8周后，FA-PEG-SPIONs的尺寸几乎没有变化，这表明颗粒尺寸非常稳定。荧光流式细胞仪和共聚焦激光扫描显微镜的结果表明，游离叶酸预处理可大大抑制FA-PEG-SPIONs-Cy5.5的细胞内摄取，这表明受体介导的内吞作用。由于受体介导的内吞作用，在通过尾静脉注射后6和24小时，在FA-PEG-SPIONs-Cy5.5的肺癌模型小鼠中观察到比PEG-SPIONs-Cy5.5更强的光学成像。

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