Synthesis and Characterization of a Nanoscale Hyaluronic Acid-Specific Probe for Magnetic Particle Imaging and Magnetic Resonance Imaging

Glycosaminoglycans (GAGs) are part of the extracellular matrix (ECM) and play a major role in maintaining their physiological function. During pathological processes, the ECM is remodeled and its GAG composition changes. Hyaluronic acid (HA) is one of the GAGs that plays an important role in pathological processes such as inflammation and cancer and is therefore an interesting target for imaging. To provide iron oxide nanoparticles (IONP) that bind to hyaluronic acid (HA) as specific probes for molecular imaging, a peptide with high affinity for HA was covalently bound to the surface of commercial IONP (synomag®-D, NH2) leading to hyaluronic acid-specific iron oxide nanoparticles (HAIONPs). Affinity measurements using a quartz crystal microbalance (QCM) showed a very high affinity of HAIONP to HA, but not to the control chondroitin sulfate (CS). HAIONPs exhibit a very high magnetic particle spectroscopy (MPS) signal amplitude, which predestines them as HA-selective tracers for magnetic particle imaging (MPI). The high relaxivity coefficient r2 also makes HAIONP suitable for magnetic resonance imaging (MRI) applications. HAIONP therefore offers excellent prerequisites for further development as a probe for the specific quantitative imaging of the HA content of the ECM in pathological areas.