title: Folate-PEG-superparamagnetic iron oxide nanoparticles for lung cancer imaging.
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 °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.
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
authors.forename: Mi-Kyong
authors.initials: MK
authors.lastname: Yoo
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Park
authors.forename: Hwang-Tae
authors.initials: HT
authors.lastname: Lim
authors.forename: Sang-Joon
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hu-Lin
authors.initials: HL
authors.lastname: Jiang
authors.forename: You-Kyoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Yun-Jaie
authors.initials: YJ
authors.lastname: Choi
authors.forename: Myung-Haing
authors.initials: MH
authors.lastname: Cho
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
mesh_terms: D000818:Animals; D001681:Biological Assay; D016923:Cell Death / Q000187:drug effects; D003911:Dextrans / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D003952:Diagnostic Imaging / Q000379:methods*; D005434:Flow Cytometry; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000633:toxicity; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D017550:Spectroscopy, Fourier Transform Infrared; D013194:Staining and Labeling
chemical_list: D003911:Dextrans; D058185:Magnetite Nanoparticles; C552831:poly(ethylene glycol)-folate; D011092:Polyethylene Glycols; D005492:Folic Acid; C065507:ferumoxides