Hyaluronic acid-modified hydrothermally synthesized iron oxide nanoparticles for targeted tumor MR imaging

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 (FI) and HA with two different molecular weights to obtain two different Fe₃O₄ 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.