Abstract

Early diagnosis of disease and follow-up of therapy is of vital importance for appropriate patient management since it allows rapid treatment, thereby reducing mortality and improving health and quality of life with lower expenditure for health care systems. New approaches include nanomedicine-based diagnosis combined with therapy. Nanoparticles (NPs), as contrast agents for in vivo diagnosis, have the advantage of combining several imaging agents that are visible using different modalities, thereby achieving high spatial resolution, high sensitivity, high specificity, morphological, and functional information. In this work, we present the development of aluminum hydroxide nanostructures embedded with polyacrylic acid (PAA) coated iron oxide superparamagnetic nanoparticles, Fe3O4@Al(OH)3, synthesized by a two-step co-precipitation and forced hydrolysis method, their physicochemical characterization and first biomedical studies as dual magnetic resonance imaging (MRI)/positron emission tomography (PET) contrast agents for cell imaging. The so-prepared NPs are size-controlled, with diameters below 250 nm, completely and homogeneously coated with an Al(OH)3 phase over the magnetite cores, superparamagnetic with high saturation magnetization value (Ms = 63 emu/g-Fe3O4), and porous at the surface with a chemical affinity for fluoride ion adsorption. The suitability as MRI and PET contrast agents was tested showing high transversal relaxivity (r2) (83.6 mM−1 s−1) and rapid uptake of 18F-labeled fluoride ions as a PET tracer. The loading stability with 18F-fluoride was tested in longitudinal experiments using water, buffer, and cell culture media. Even though the stability of the 18F-label varied, it remained stable under all conditions. A first in vivo experiment indicates the suitability of Fe3O4@Al(OH)3 nanoparticles as a dual contrast agent for sensitive short-term (PET) and high-resolution long-term imaging (MRI).

Highlights

  • Advances in physics and engineering have allowed the development of non-invasive imaging techniques that gave rise to a striking medical revolution in which detailed physiology, pathology, and functionality of the human body could be revealed with detailed precision non-invasively

  • We present the development of aluminum hydroxide nanostructures embedded with polyacrylic acid (PAA) coated iron oxide superparamagnetic nanoparticles, Fe3O4@Al(OH)3, synthesized by a two-step co-precipitation and forced hydrolysis method, their physicochemical characterization and first biomedical studies as dual magnetic resonance imaging (MRI)/positron emission tomography (PET) contrast agents for cell imaging

  • Total Ionic Strength Adjustment Buffer solution (TISAB III), phosphate-buffered saline (PBS), TrypLE, high-glucose Dulbecco’s Modified Eagle’s Medium (DMEM) containing GlutaMax, fetal bovine serum (FBS), and penicillin-streptomycin were obtained from Gibco-Invitrogen (Gibco-InvitrogenTM-Fisher, Carlsbad, CA, USA), Milli-Q (Millipore®, Burlington, MA, USA) deionized water was used in all the experiments

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Summary

Introduction

Advances in physics and engineering have allowed the development of non-invasive imaging techniques that gave rise to a striking medical revolution in which detailed physiology, pathology, and functionality of the human body could be revealed with detailed precision non-invasively. Magnetite iron oxide nanoparticles (Fe3O4 NPs) have attracted considerable interest as negative MRI contrast agents due to their excellent magnetic properties, low toxicity, biocompatibility, and biodegradability compared to the other magnetic NPs (MnFe2O4, ZnFe2O4, CoFe2O4, etc.) [11]. For this application, Fe3O4 nanoparticles with a narrow size distribution, superparamagnetic behavior, and specific surface modification are desired [12,13]. The use of an inorganic shell material that introduces stability, functionality, and water-solubility is desirable

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