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

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.

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 transmis sion electron microscopy, X-ray powder diffraction, UV-vis absorption spectra, and Fourier transform infrared absorption (FTIR) spectra to characterize the prepared nanocom-plex 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.

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.

A T₁-T₂ dual-mode contrast agent, Fe₃O₄@mSiO₂/PDDA/BSA-Gd₂O₃ nano-complex, 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.