Journal
BIOMATERIALS
Volume 35, Issue 11, Pages 3666-3677Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.01.011
Keywords
Polyethyleneimine; Iron oxide nanoparticles; Hyaluronic acid; Targeting; MR imaging; Tumors
Funding
- Fund of the Science and Technology Commission of Shanghai Municipality [11nm0506400, 12520705500, 20111, 06]
- National Natural Science Foundation of China [81341050, 81101150, 21273032]
- Program for New Century Excellent Talents in University
- State Education Ministry
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of High Learning
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We report a polyethyleneimine (PEI)-mediated approach to synthesizing hyaluronic acid (HA)-targeted magnetic iron oxide nanoparticles (Fe3O4 NPs) for in vivo targeted tumor magnetic resonance (MR) imaging applications. In this work, Fe3O4 NPs stabilized by PEI were first synthesized via a one-pot hydrothermal method. The formed PEI-stabilized Fe3O4 NPs were then modified with fluorescein isothiocyanate (Fl) and HA with two different molecular weights to obtain two different Fe304 NPs (Fe3O4 -PEI-FI-HA(6K) and Fe3O4 -PEI-FI-HA(31K) NPs) with a size of 15-16 nm. The formed HA-modified multifunctional Fe3O4 NPs were characterized via different techniques. We show that the multifunctional Fe3O4 NPs are water-dispersible and colloidal stable in different aqueous media. In vitro cell viability and hemolysis studies reveal that the particles are quite cytocompatible and hemocompatible in the given concentration range. Furthermore, confocal microscopy and flow cytometry data demonstrate that HA-targeted Fe3O4 NPs are able to be uptaken specifically by cancer cells overexpressing CD44 receptors, and be used as efficient probes for targeted MR imaging of cancer cells in vitro and xenografted tumor models in vivo. With the tunable amine-based conjugation chemistry, the PEI-stabilized Fe3O4 NPs may be functionalized with other biological ligands or drugs for diagnosis and therapy of different biological systems. (C) 2014 Elsevier Ltd. All rights reserved.
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