Journal
BIOMATERIALS SCIENCE
Volume 3, Issue 5, Pages 721-732Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5bm00037h
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Funding
- National Natural Science Foundation of China [21273032, 81101150, 81341050, 81371623]
- Sino-German Center for Research Promotion [GZ899]
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning
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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 center dot 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 r(2) relaxivity (550.04 mM(-1) s(-1)) and RGD-mediated targeting specificity to alpha(v)beta(3) integrin-overexpressing cancer cells as confirmed by flow cytometry and confocal microscopy, the developed multifunctional Fe3O4@PEI center dot NHAc-FI-PEG-RGD NPs are able to be used as a highly efficient nanoprobe for targeted MR imaging of alpha(v)beta(3) 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.
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