A specific “switch-on” type magnetic resonance nanoprobe with distance-dominate property for high-resolution imaging of tumors

Abstract

Magnetic resonance imaging (MRI) contrast agents (CAs) are a powerful tool for disease diagnosis. However, the “always on” state of clinically used CAs affects the specificity of tumor MR imaging in vivo. Herein, we constructed a tumor microenvironment “switch-on” type nanoprobe (TSN) with a distance-dominated property for specific tumor MR imaging, by employed a superparamagnetic hollow mesoporous iron oxide nanoparticle (HMIN) as the carrier to encapsulate T1-field CA (Gd), followed by blocking of the mesoporous channel with biocompatible hyaluronic acid (HA). In normal tissues with low-level hyaluronidase (HAase), Gd was restricted inside the HMIN, the distance between the two substances became quite close, and the magnetic field of Gd was interfered by the superparamagnetic HMIN, turning “off” the T1-field signal is “turned off”; in contrast, in tumor tissues with high-level HAase, Gd was rapidly released from the HMIN by specifically responding to overexpressed HAase, the distance between the two substances became significantly enlarged, and the magnetic field of Gd was not interfered, thus turning “on” the T1-field signal to achieve tumor-specific “switch on” MR imaging in a distance-controlled manner. The tumor/normal T1-field signal ratio after TSN treatment increased by 1.9-fold compared with free Gd-DTPA, because of its high Gd loading content, tumor-targeting ability of HA and the tumor-specific property. This distance-controlled switchable nanoprobe provides an alternative strategy for high-resolution tumor imaging with high specificity.