T<sub>1</sub>–T<sub>2</sub> molecular magnetic resonance imaging of renal carcinoma cells based on nano-contrast agents

Abstract

Background: The development of T 1 –T 2 dual contrast agent (CA) favors the visualization of the lesion in a more accurate and reliable manner by magnetic resonance imaging (MRI). The relaxivity and the interference between T 1 and T 2 CA are the main concerns for their design. Methods: In this work, we constructed an Fe 3 O 4 @mSiO 2 /PDDA/BSA-Gd 2 O 3 nanocomplex where BSA-Gd 2 O 3 NPs and Fe3O4 NPs were chosen as T 1 and T 2 MRI CAs and a 20 nm mesoporous silica (mSiO 2 ) nanoshell was introduced to reduce the interference between them. We performed transmis­sion electron microscopy, X-ray powder diffraction, UV-vis absorption spectra, and Fourier transform infrared absorption (FTIR) spectra to characterize the prepared nanocomplex and MRI scanning to evaluate their MRI behaviors. Furthermore, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and hematologic and biochemical analyses were introduced to evaluate their in vitro and in vivo toxicity. Finally, the specific MRI of 786-0 cells with Fe 3 O 4 @mSiO 2 /PDDA/BSA-Gd 2 O 3 -AS1411 nanoprobe in vitro was realized. In vivo biodistribution of Fe 3 O 4 @mSiO 2 /PDDA/BSA-Gd 2 O 3 nanocomplex in the mouse was determined by the quantification of the Gd element by inductively coupled plasma-mass spectrometry. Results: The prepared Fe 3 O 4 @mSiO 2 /PDDA/BSA-Gd 2 O 3 nanocomplex possessed high longitudinal ( r 1 =11.47 mM s -1 Gd) and transverse ( r 2 =195.1 mM s -1 Fe) relaxivities, enabling its use as a T1–T2 dual contrast agent for MRI. MTT testing and hematologic and biochemical analysis indicated the good biocompatibility of [email protected] /PDDA/BSA-Gd2O3 nanocomplex in vitro and in vivo. After further conjugation with AS1411 aptamer, they could target tumor cells successfully by T 1 and T 2 MRI in vitro. The possible metabolic pathway of the tail vein-injected Fe 3 O 4 @mSiO 2 /PDDA/BSA-Gd 2 O 3 nanocomplex in mouse was mainly via kidney. Conclusion: A T 1 –T 2 dual-mode contrast agent, Fe 3 O 4 @mSiO 2 /PDDA/BSA-Gd 2 O 3 nanocomplex, was developed and its good performance for tumor cell targeting in vitro and kidney contrast-enhanced MRI in mice indicated its promising potential as an effective T 1 –T 2 dual-mode contrast agent for in vivo MRI with self-confirmation. Keywords: molecular magnetic resonance imaging, nano-contrast agent, aptamer, T 1 –T 2 , MRI