Yoo, Mi-Kyong; Park, In-Kyu; Lim, Hwang-Tae; Lee, Sang-Joon; Jiang, Hu-Lin; Kim, You-Kyoung; Choi, Yun-Jaie; Cho, Myung-Haing; Cho, Chong-Su
Acta biomaterialia
2012Aug ; 8 ( 8 ) :3005-13.
PMID : 22543005
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Yoo, Mi-Kyong -
Park, In-Kyu -
Lim, Hwang-Tae -
Lee, Sang-Joon -
Jiang, Hu-Lin -
Kim, You-Kyoung -
Choi, Yun-Jaie -
Cho, Myung-Haing -
Cho, Chong-Su -
ABSTRACT
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 degrees 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. CI - Copyright (c) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Magnetic nanoparticles; Folate; Poly(ethylene glycol); Lung cancer; Imaging
MESH
Animals, Biological Assay, Cell Death/drug effects, *Dextrans/chemical synthesis/chemistry/toxicity, Diagnostic Imaging/*methods, Flow Cytometry, Folic Acid/*analogs & derivatives/chemical synthesis/chemistry/toxicity, Lung Neoplasms/*diagnosis/pathology, Magnetic Resonance Spectroscopy, *Magnetite Nanoparticles/chemistry/toxicity, Male, Mice, Microscopy, Confocal, *Nanoparticles/chemistry/toxicity/ultrastructure, Particle Size, *Polyethylene Glycols/chemical synthesis/chemistry/toxicity, Spectroscopy, Fourier Transform Infrared, Staining and Labeling
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