Polyethyleneimine-mediated synthesis of folic acid-targeted iron oxide nanoparticles for in vivo tumor MR imaging.
We report a facile polyethyleneimine (PEI)-mediated approach to synthesizing folic acid (FA)-targeted magnetic iron oxide nanoparticles (Fe3O4 NPs) for in vivo magnetic resonance (MR) imaging of tumors. In this study, stable PEI-coated Fe3O4 NPs were prepared by a one-pot hydrothermal route. The aminated Fe3O4 NPs with PEI coating enabled covalent conjugation of fluorescein isothiocyanate (FI) and folate-conjugated polyethylene glycol (PEG) with one end of carboxyl groups (FA-PEG-COOH). Followed by final acetylation, FA-targeted PEGylated Fe3O4 NPs (Fe3O4-PEI-Ac-FI-PEG-FA NPs) were formed. The formed multifunctional Fe3O4 NPs were characterized via different techniques. We show that the PEI-mediated approach along with the PEGylation conjugation enables the generation of water-dispersible and stable multifunctional Fe3O4 NPs, and the particles are quite cytocompatible and hemocompatible in the given concentration range as confirmed by in vitro cytotoxicity assay, cell morphology observation, and hemolysis assay. In addition, flow cytometry and confocal microscopy data show that the multifunctional Fe3O4 NPs are able to target a model cancer cell line (KB cells) overexpressing FA receptors in vitro. Importantly, the FA-targeted Fe3O4 NPs are able to be used as an efficient nanoprobe for MR imaging of cancer cells in vitro and a xenografted tumor model in vivo via an active FA targeting pathway. With the facile PEI-mediated formation strategy and PEGylation conjugation chemistry, the Fe3O4 NPs may be multifunctionalized with other biological ligands for MR imaging of different biological systems.
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, PR China.
Jingchao
J
Li
Linfeng
L
Zheng
Hongdong
H
Cai
Wenjie
W
Sun
Mingwu
M
Shen
Guixiang
G
Zhang
Xiangyang
X
Shi
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005290:Ferric Compounds / Q000737:chemistry*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D005492:Folic Acid / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*
D005290:Ferric Compounds; C069224:fluorescein isothiocyanate-polyethylenimine; C000499:ferric oxide; D011094:Polyethyleneimine; D005492:Folic Acid; D016650:Fluorescein-5-isothiocyanate
Folic acid; Iron oxide nanoparticles; Magnetic resonance imaging; Polyethyleneimine; Targeting; Tumors