title: Facile synthesis of RGD peptide-modified iron oxide nanoparticles with ultrahigh relaxivity for targeted MR imaging of tumors.
abstract: We report the facile synthesis of arginine-glycine-aspartic acid (RGD) peptide-targeted iron oxide (Fe3O4) nanoparticles (NPs) with ultrahigh relaxivity for in vivo tumor magnetic resonance (MR) imaging. In this study, stable polyethyleneimine (PEI)-coated Fe3O4 NPs were first prepared by a mild reduction route. The formed aminated Fe3O4 NPs with PEI coating were sequentially conjugated with fluorescein isothiocyanate (FI) and polyethylene glycol (PEG)-RGD segment, followed by acetylation of the remaining PEI surface amines. The thus-formed Fe3O4@PEI·NHAc-FI-PEG-RGD NPs were characterized via different techniques. We show that the multifunctional RGD-targeted Fe3O4 NPs with a mean size of 9.1 nm are water-dispersible, colloidally stable, and hemocompatible and cytocompatible in the given concentration range. With the displayed ultrahigh r2 relaxivity (550.04 mM(-1) s(-1)) and RGD-mediated targeting specificity to αvβ3 integrin-overexpressing cancer cells as confirmed by flow cytometry and confocal microscopy, the developed multifunctional Fe3O4@PEI·NHAc-FI-PEG-RGD NPs are able to be used as a highly efficient nanoprobe for targeted MR imaging of αvβ3 integrin-overexpressing cancer cells in vitro and the xenografted tumor model in vivo. Given the versatile PEI amine-enabled conjugation chemistry, the developed PEI-coated Fe3O4 NPs may be functionalized with other biological ligands or drugs for various biomedical applications, in particular, the diagnosis and therapy of different types of cancer.
authors.affiliation: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P. R. China. xshi@dhu.edu.cn mingwu_shen@yahoo.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.forename: Jingchao
authors.initials: J
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.forename: Yu
authors.initials: Y
authors.lastname: Luo
authors.forename: Ling
authors.initials: L
authors.lastname: Ding
authors.forename: Wenjie
authors.initials: W
authors.lastname: Sun
authors.forename: Guixiang
authors.initials: G
authors.lastname: Zhang
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
mesh_terms: D001686:Biological Phenomena; D045744:Cell Line, Tumor; D005290:Ferric Compounds / Q000737:chemistry*; D006461:Hemolysis; D006801:Humans; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053768:Metal Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D005290:Ferric Compounds; D008024:Ligands; D009842:Oligopeptides; C000499:ferric oxide; C047981:arginyl-glycyl-aspartic acid; D011094:Polyethyleneimine