Magnetic Field-Optimized Paramagnetic Nanoprobe for <i>T</i><sub>2</sub>/<i>T</i><sub>1</sub> Switchable Histopathological-Level MRI
Linlin Huo, Jie Zeng, Zhenyu Wang, Xin Sun, Yu Guo, Zhile Cao, Shiqi Zhu, Mingya Tan, Muyao Li, X. Chen, Zhenghuan Zhao
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 T 2 relaxivities and achieve effective T 2 / T 1 switchable MRI imaging of tumors. Compared to traditional contrast agents with high saturation magnetization to enhance T 2 relaxivities, 1-D MONPs with weak M s effectively increase the inhomogeneity of the local magnetic field and exhibit obvious T 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 T 2 relaxivities. Furthermore, the GSH responsiveness ensures 1-D MONPs with sensitive switching from the T 2 to T 1 mode in vitro 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 T 2 relaxivity of magnetic nanoparticles and construct switchable MRI CAs, offering high tumor-to-normal tissue contrast signal for early and accurate diagnosis.