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

Mi-Kyong Yoo, In-Kyu Park, Hwang-Tae Lim, Sang-Joon Lee, Hu-Lin Jiang, You-Kyoung Kim, Yun-Jaie Choi, Myung-Haing Cho, Chong-Su Cho
Acta Biomaterialia 2012, 8 (8): 3005-13
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.

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