Hyaluronidase-Sensitive SPIONs for MR/Optical Dual Imaging Nanoprobes

This study developed new enzyme-specific superparamagnetic iron oxide nanoparticles (SPIONs) with potential as a multimodal probe in magnetic resonance (MR) imaging and optical imaging. For the MR/optical dual imaging, SPIONs were coated with near-infrared fluorescence dye (Cy5.5)-labeled hyaluronic acid (Cy5.5-HA), which could be readily degraded by hyaluronidase (HAdase). The presence of HA on the coated SPION was confirmed using FTIR, X-ray diffraction, and thermogravimetric analysis. Physicochemical analyses of Cy5.5-HA-coated SPIONs (Cy5.5-HA-SPIONs) demonstrated their higher colloidal stability and T2 relaxivity than bare SPIONs. When Cy5.5-HA-SPIONs were exposed to the MR instrument for the phantom test, the dark intensity of their T2-weighted image increased in a Fe concentration-dependent manner, suggesting potential as the MR probe. To examine their ability as the enzyme-sensitive optical probe, the fluorescent signals of Cy5.5-HA-SPIONs were measured in the absence or presence of HAdase. In the absence of HAdase, Cy5.5-HA-SPIONs showed a negligible fluorescent signal due to possible quenching between a SPION and fluorescence dye, and self-quenching effect of Cy5.5 molecules. On the other hand, in the presence of HAdase, the fluorescent signal of Cy5.5-HA-SPIONs increased dramatically as a function of the HAdase concentration, resulting from the degradation of the HA backbone. These results suggest that the Cy5.5-HA-SPION is useful as a multimodal nanoprobe for MR imaging and HAdase-sensitive optical imaging.