Manganese-Based Layered Double Hydroxide Nanoparticles as a T1 -MRI Contrast Agent with Ultrasensitive pH Response and High Relaxivity

Abstract

Recently, Mn(II)-containing nanoparticles have been explored widely as an attractive alternative to Gd(III)-based T₁ -weighted magnetic resonance imaging (MRI) contrast agents (CAs) for cancer diagnosis. However, as far as it is known, no Mn-based MRI CAs have been reported to sensitively respond to a very weakly acidic environment (pH 6.5-7.0, i.e., the pH range in a tumor microenvironment) with satisfactory imaging performance. Here, recently devised pH-ultrasensitive Mn-based layered double hydroxide (Mn-LDH) nanoparticles with superb longitudinal relaxivity (9.48 mm^-1 s^-1 at pH 5.0 and 6.82 mm^-1 s^-1 at pH 7.0 vs 1.16 mm^-1 s^-1 at pH 7.4) are reported, which may result from the unique microstructure of Mn ions in Mn-LDH, as demonstrated by extended X-ray absorption fine structure. Further in vivo imaging reveals that Mn-LDH nanoparticles show clear MR imaging for tumor tissues in mice for 2 d post intravenous injection. Thus, this novel Mn-doped LDH nanomaterial, together with already demonstrated capacity for drug and gene delivery, is a very potential theranostic agent for cancer diagnosis and treatment.

Keywords: contrast agents; high relaxivity; pH response; theranostic agents.