Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
Acta Biomater. 2012 Aug;8(8):3005-13. doi: 10.1016/j.actbio.2012.04.029. Epub 2012 Apr 24.
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.
虽然超顺磁性氧化铁纳米粒子（SPIONs）已被广泛应用于生物医学领域，但由于其快速的血液清除率、不稳定性和主动靶向性，限制了其在临床试验中的应用。本研究旨在开发稳定且具有肺癌靶向性的 SPIONs。为此，首先合成了叶酸（FA）-聚乙二醇（PEG），然后通过 FA-PEG 与氨基硅烷修饰的 SPIONs 反应制备了 FA-PEG-SPIONs。FA-PEG-SPIONs 用 Cy5.5 进行光学成像标记。为了证实主动靶向性，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。FA-PEG-SPIONs 在 4°C 下放置长达 8 周后，粒径变化很小，表明粒径非常稳定。荧光流式细胞术和共聚焦激光扫描显微镜的结果表明，FA-PEG-SPIONs-Cy5.5 的细胞内摄取被游离叶酸预处理显著抑制，提示受体介导的内吞作用。与 PEG-SPIONs-Cy5.5 相比，静脉注射尾静脉后 6 和 24 小时，肺癌模型小鼠中 FA-PEG-SPIONs-Cy5.5 的光学成像更强，这是由于受体介导的内吞作用。
