A Blood-Labyrinth Barrier-Crossing Nanoprobe for Sensitive Magnetic Resonance Imaging of the Inner Ear

Contrast-enhanced inner ear magnetic resonance imaging (MRI) provides clinicians with powerful structural and pathological information for the diagnosis of inner ear diseases. However, currently used gadolinium (Gd) chelate-mediated contrast-enhanced MRI conveys insufficient inner ear specificity, and Gd-based contrast agents have a short body retention time and cause severe ototoxicity. Herein, we present the rational design of a sensitive inner ear-specific nanoprobe (I-PUSPIO) for inner ear MRI that is composed of an ultrasmall iron oxide core, the IETP2 peptide, and polyethylene glycol. Such a well-defined nanostructure endows it with blood-labyrinth barrier crossing capacity, leading to a high accumulation rate in the inner ear and prolonged body retention. In vivo I-PUSPIO can enhance high-resolution MRI of cochlear tissue and shows no evidence of toxicity. This study demonstrates the potential of I-PUSPIO as a sensitive contrast agent for inner ear MRI in clinical settings.