Abstract
Colloidal stability of magnetic iron oxide nanoparticles (MNP) in physiological environments is crucial for their (bio)medical application. MNP are potential contrast agents for different imaging modalities such as magnetic resonance imaging (MRI) and magnetic particle imaging (MPI). Applied as a hybrid method (MRI/MPI), these are valuable tools for molecular imaging. Continuously synthesized and in-situ stabilized single-core MNP were further modified by albumin coating. Synthesizing and coating of MNP were carried out in aqueous media without using any organic solvent in a simple procedure. The additional steric stabilization with the biocompatible protein, namely bovine serum albumin (BSA), led to potential contrast agents suitable for multimodal (MRI/MPI) imaging. The colloidal stability of BSA-coated MNP was investigated in different sodium chloride concentrations (50 to 150 mM) in short- and long-term incubation (from two hours to one week) using physiochemical characterization techniques such as transmission electron microscopy (TEM) for core size and differential centrifugal sedimentation (DCS) for hydrodynamic size. Magnetic characterization such as magnetic particle spectroscopy (MPS) and nuclear magnetic resonance (NMR) measurements confirmed the successful surface modification as well as exceptional colloidal stability of the relatively large single-core MNP. For comparison, two commercially available MNP systems were investigated, MNP-clusters, the former liver contrast agent (Resovist), and single-core MNP (SHP-30) manufactured by thermal decomposition. The tailored core size, colloidal stability in a physiological environment, and magnetic performance of our MNP indicate their ability to be used as molecular magnetic contrast agents for MPI and MRI.
Highlights
Molecular imaging provides an integrative technology to study biological processes using non-invasive visualization of specific molecules in vivo [1] with the aim of early disease diagnosis and treatment evaluation [2]
We demonstrate that surface modification of continuously synthesized single-core magnetic iron oxide nanoparticles (MNP) with bovine serum albumin (BSA) effectively improves their stability and ensures a robust performance as tracers in molecular imaging
We show that centrifugation significantly improves the magnetic performance of the as-synthesized MNP in Section 2.1, demonstrate the structural and magnetic changes by surface modification using a BSAcoating in Section 2.2, and present the steady stability of the BSA-coated system in different physiological saline concentrations together with the maintenance of the powerful magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) imaging capability of this MNP system
Summary
Molecular imaging provides an integrative technology to study biological processes using non-invasive visualization of specific molecules in vivo [1] with the aim of early disease diagnosis and treatment evaluation [2] To this end, numerous imaging techniques have been developed for molecular imaging such as magnetic resonance imaging (MRI) [1], positron emission tomography (PET) [3], computed tomography (CT) [4], single-photon emission computed tomography (SPECT) [5,6], or ultrasound (US) [7]. MRI is not specific to molecules and requires the use of contrast agents or tracers to provide specificity and sensitivity for molecular imaging Due to their magnetic properties, contrast agents such as paramagnetic Gd-compounds can shorten the T1 (or longitudinal) and T2 (or transverse) relaxation time of neighboring water protons.
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