One-pot preparation of hydrophilic manganese oxide nanoparticles as T1 nano-contrast agent for molecular magnetic resonance imaging of renal carcinoma in vitro and in vivo

Abstract

Magnetic resonance imaging (MRI) contrast agents have become a necessary part for clinical practice to improve the sensitivity for the diagnosis of small lesions and injuries. Among them, manganese oxide nanoparticle (MnO NPs)-based MRI contrast agent attracts more and more attention because of their better performance in the detection of brain disease and positive enhancement in T1-weighted image. However, the relatively low r1 relaxivity and complex synthetic route hampered their wider applications. In this work, we proposed a one-pot approach to prepare hydrophilic MnO NPs via a polyol-like method with poly (ethylene glycol) (PEG) as both a solvent and surfactant. The obtained PEG-MnO NPs displayed a high T1 relaxivity and a low r2/r1 ratio (12.942s−1 mM−1 and 4.66) at 3.0T, which was three times that of the clinical used contrast agent, Magnevist (Gd-DTPA). Additionally, when exposed to the simulated body fluid (SBF), acidic environment or glutathione, PEG-MnO NPs kept stable, favoring their further biological applications. Then, to explore their use for the molecular magnetic resonance imaging of 786-0 renal carcinoma, amino group modified AS1411 aptamer as the targeting molecule was introduced to conjugate with PEG-MnO NPs via covalent coupling reaction. The fabricated nanoprobe, AS1411-PEG-MnO, could clearly visualize 786-0 renal carcinoma cells with MRI in vitro. Furthermore, compared with PEG-MnO NPs, AS1411-PEG-MnO nanoprobe presented a prolonged retention in 786-0 renal carcinoma tumor in vivo. The intravenously injected nanoprobes were eventually excreted from the body through the renal clearance route. These results indicated the potential promising of PEG-MnO NPs as an alternative contrast agent in MRI scanning.