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 T 1 and T 2 relaxivity. The in vitro MRI demonstrated that the MgMnAl-LDH@IO NP could act as a pH-sensitive contrast agent for both T 1- and T 2-weighted MR imaging (r 1, 5.67 mM–1 s–1 under pH 5.0 and 1.98 mM–1 s–1 under pH 7.4; r 2, 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 T 1- and T 2-weighted MR imaging of tumor tissues in breast-tumor-bearing mice. The facile synthetic method, desirable biocompatibility, sensitive stimuli response, and concurrently enhanced T 1/T 2 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.

Layered Double Hydroxide Nanoparticles to Overcome the Hydrophobicity of Ellagic Acid: An Antioxidant Hybrid Material

“…The general formula is stated as [M(II) 1-x M(III) x (OH) 2 ][A n-•mH 2 O], where M(II) and M(III) are divalent and trivalent metal ions and A n-•mH 2 O is the interlamellar (i.e., intercalated), charge-neutralizing anion in hydrated state [2]. Through tuning the composition of LDH and their composites with other materials [3], they can be used in a variety of applications including adsorbents for water purification [4,5], light emitters [6], corrosion-resistant coating material [7], contrast agents [8], solid support for bioactive substances [9,10], catalyst carriers [11] and catalysts in organic reactions [12,13], or in water splitting [14,15].…”

Biocompatible Hydrotalcite Nanohybrids for Medical Functions

“…Hydrotalcite nanohybrids have been extensively explored in biomedical fields especially for drug/gene delivery, cancer therapy and bio-imaging based on their two-dimensional (2D) layered structure, good biocompatibility and biodegradability [25][26][27][28][29][30][31][32]. LDHs comprise a unique class of 2D layered material, since they consist of positively charged brucite (Mg[OH] 2 )-like metal hydroxide layers in which metal divalent cations are partially substituted by trivalent ones and charge-balancing interlayer anions located in the hydrated gallery between the layers.…”

Functional Layered Double Hydroxide Nanohybrids for Biomedical Imaging

“…T 1 contrast agents are used to enhance longitudinal relaxation processes, producing brighter signals by using a paramagnetic material such as Gd 3+ or Mn 2+ metal ion [10,11,12,79] to shorten the T 1 . On the other hand, T 2 contrast agents are made of a superparamagnetic material such as iron oxide nanoparticles [12,38,80,81], which can enhance the transverse relaxation processes by shortening T 2 and thus result in darker signals. Studies are underway on advanced contrast agents that can boost up imaging sensitivity through the contrast enhancement in regions of interest in T 1 or T 2 images.…”

“…The therapeutic functions including drug delivery and gene therapy along with imaging functions were also widely investigated. Most recently, the concurrently enhanced T 1 /T 2 -weighted contrast agent was reported and has attracted special attention for clinical applications in MRI with improved accuracy [12].…”

“…Since intercalative nanohybrids of DNA in LDH was proposed as “bio-inorganic nanohybrids” for the first time in 1999 [8], LDHs have received continuous attentions in biomedical applications with multifunctional nanohybrid systems. A representative research is related to nano contrast agent systems that are essential for the development of bio-imaging technology [9,10,11,12]. Successful manipulation on the nanometer scale of LDH can provide novel perspectives in the design of multifunctional nanohybrids, which open up a promising field for applications in bio-imaging with simultaneously effectual therapeutic functions.…”