Manganese-Based Magnetic Layered Double Hydroxide Nanoparticle: A pH-Sensitive and Concurrently Enhanced T1/T2-Weighted Dual-Mode Magnetic Resonance Imaging Contrast Agent.

Abstract

The interference effect and lack of selectivity are the bottlenecks for dual-mode magnetic resonance imaging (MRI) contrast agent development. To address these challenges and overcome the single mode imaging contrast limitations, a novel MgMnAl-layered double hydroxide@iron oxide nanoparticle (MgMnAl-LDH@IO NP) has been successfully synthesized as a concurrently enhanced dual-mode contrast agent for MRI of tumor tissues with sensitive pH response and high efficacy. The attachment of iron oxide nanoparticles on the surface of MgMnAl-LDH NPs led to the increased local magnetic field intensity, inducing the concurrent enhancement of both T1 and T2 relaxivity. The in vitro MRI demonstrated that the MgMnAl-LDH@IO NP could act as a pH-sensitive contrast agent for both T1- and T2-weighted MR imaging (r1, 5.67 mM-1 s-1 under pH 5.0 and 1.98 mM-1 s-1 under pH 7.4; r2, 369.12 mM-1 s-1 under pH 5.0 and 225.29 mM-1 s-1 under pH 7.4). The biocompatibility of the dual-mode contrast agent was revealed by the cytotoxicity test on fibroblast cells. Further in vivo dual-mode MR imaging exhibited that the MgMnAl-LDH@IO NP showed clear T1- and T2-weighted MR imaging of tumor tissues in breast-tumor-bearing mice. The facile synthetic method, desirable biocompatibility, sensitive stimuli response, and concurrently enhanced T1/T2 MRI signals both in vitro and in vivo encourage the great potential biomedical and clinical applications of MgMnAl-LDH@IO NP in MR imaging with improved accuracy.