Porous Silica Nanospheres with a Confined Mono(aquated) Mn(II)-Complex: A Potential T 1–T 2 Dual Contrast Agent for Magnetic Resonance Imaging

• Published in: ACS applied bio materials Vol. 4; no. 12; pp. 8356 - 8367
• Main Authors: Mallik, Riya, Saha, Muktashree, Mukherjee, Chandan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.12.2021
• Subjects: Contrast Media - chemistry; HeLa Cells; Humans; Magnetic Resonance Imaging - methods; Manganese - chemistry; Nanospheres; Porosity; Silicon Dioxide; Water - chemistry; magnetic resonance imaging; relaxivity; porous silica nanoparticles; T 1−T 2 contrast agents; Mn(II)-complex; T1−T2 contrast agents
• ISSN: 2576-6422; 2576-6422
• DOI: 10.1021/acsabm.1c00937

Magnetic resonance imaging has emerged as an indispensable imaging modality for the early-stage diagnosis of many diseases. The imaging in the presence of a contrast agent is always advantageous, as it mitigates the low-sensitivity issue of the measurements and provides excellent contrast in the acquired images even in a short acquisition time. However, the stability and high relaxivity of the contrast agents remained a challenge. Here, molecules of a mononuclear, mono­(aquated), thermodynamically stable [log K MnL = 14.80(7) and pMn = 8.97] Mn­(II)-complex (1), based on a hexadentate pyridine-picolinate unit-containing ligand (H2PyDPA), were confined within a porous silica nanosphere in a noncovalent fashion to render a stable nanosystem, complex 1@SiO2NP. The entrapped complex 1 (complex 1@SiO2) exhibited r 1 = 8.46 mM–1 s–1 and r 2 = 33.15 mM–1 s–1 at pH = 7.4, 25 °C, and 1.41 T in N-(2-hydroxyethyl)­piperazine-N′-ethanesulfonic acid buffer. The values were about 2.9 times higher compared to the free (unentrapped)-complex 1 molecules. The synthesized complex 1@SiO2NP interacted significantly with albumin protein and consequently boosted both the relaxivity values to r 1 = 24.76 mM–1 s–1 and r 2 = 63.96 mM–1 s–1 at pH = 7.4, 37 °C, and 1.41 T. The kinetic inertness of the entrapped molecules was established by recognizing no appreciable change in the r 1 value upon challenging complex 1@SiO2NP with 30 and 40 times excess of Zn­(II) ions at pH 6 and 25 °C. The water molecule coordinated to the Mn­(II) ion in complex 1@SiO2 was also impervious to the physiologically relevant anions (bicarbonate, biphosphate, and citrate) and pH of the medium. Thus, it ensured the availability of the inner-coordination site of complex 1 for the coordination of water molecules in the biological media. The concentration-dependent changes in image intensities in T 1- and T 2-weighted phantom images and uptake of the nanoparticles by the HeLa cell put forward the biocompatible complex 1@SiO2NP as a potential dual-mode MRI contrast agent, an alternative to Gd­(III)-containing contrast agents.