Magnetic Field-Optimized Paramagnetic Nanoprobe for <i>T</i>₂/<i>T</i>₁ Switchable Histopathological-Level MRI.

Abstract

Traditional magnetic resonance imaging (MRI) contrast agents (CAs) are a type of "always on" system that accelerates proton relaxation regardless of their enrichment region. This "always on" feature leads to a decrease in signal differences between lesions and normal tissues, hampering their applications in accurate and early diagnosis. Herein, we report a strategy to fabricate glutathione (GSH)-responsive one-dimensional (1-D) manganese oxide nanoparticles (MONPs) with improved <i>T</i>₂ relaxivities and achieve effective <i>T</i>₂/<i>T</i>₁ switchable MRI imaging of tumors. Compared to traditional contrast agents with high saturation magnetization to enhance <i>T</i>₂ relaxivities, 1-D MONPs with weak <i>M</i>_s effectively increase the inhomogeneity of the local magnetic field and exhibit obvious <i>T</i>₂ contrast. The inhomogeneity of the local magnetic field of 1-D MONPs is highly dependent on their number of primary particles and surface roughness according to Landau-Lifshitz-Gilbert simulations and thus eventually determines their <i>T</i>₂ relaxivities. Furthermore, the GSH responsiveness ensures 1-D MONPs with sensitive switching from the <i>T</i>₂ to <i>T</i>₁ mode <i>in vitro</i> and subcutaneous tumors to clearly delineate the boundary of glioma and metastasis margins, achieving precise histopathological-level MRI. This study provides a strategy to improve <i>T</i>₂ relaxivity of magnetic nanoparticles and construct switchable MRI CAs, offering high tumor-to-normal tissue contrast signal for early and accurate diagnosis.