T1–T2 molecular magnetic resonance imaging of renal carcinoma cells based on nano-contrast agents

Abstract

Jingjing Li,1,2,* Jia You,2,3,* Chen Wu,2 Yue Dai,1 Meilin Shi,2 Lina Dong,2 Kai Xu1,2 1Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, People’s Republic of China; 2School of Medical Imaging, Xuzhou Medical University, Xuzhou 221004, People’s Republic of China; 3Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, People’s Republic of China *These authors contributed equally to this work Background: The development of T1–T2 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 T1 and T2 CA are the main concerns for their design. Methods: In this work, we constructed an Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex where BSA-Gd2O3 NPs and Fe3O4 NPs were chosen as T1 and T2 MRI CAs and a 20 nm mesoporous silica (mSiO2) 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 Fe3O4@mSiO2/PDDA/BSA-Gd2O3-AS1411 nanoprobe in vitro was realized. In vivo biodistribution of Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex in the mouse was determined by the quantification of the Gd element by inductively coupled plasma-mass spectrometry. Results: The prepared Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex possessed high longitudinal (r1=11.47 mM s-1 Gd) and transverse (r2=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 Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex in vitro and in vivo. After further conjugation with AS1411 aptamer, they could target tumor cells successfully by T1 and T2 MRI in vitro. The possible metabolic pathway of the tail vein-injected Fe3O4@mSiO2/PDDA/BSA-Gd2O3 nanocomplex in mouse was mainly via kidney. Conclusion: A T1–T2 dual-mode contrast agent, Fe3O4@mSiO2/PDDA/BSA-Gd2O3 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 T1–T2 dual-mode contrast agent for in vivo MRI with self-confirmation. Keywords: molecular magnetic resonance imaging, nano-contrast agent, aptamer, T1–T2, MRI

Keywords

• molecular magnetic resonance imaging
• nano-contrast agent
• aptamer
• T1-T2