T(1)–T(2) molecular magnetic resonance imaging of renal carcinoma cells based on nano-contrast agents

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 Fe(3)O(4) 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 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 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 T(1)–T(2) dual contrast agent for MRI. MTT testing and hematologic and biochemical analysis indicated the good biocompatibility of Fe(3)O(4)@mSiO(2)/PDDA/BSA-Gd(2)O(3) 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) 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 T(1)–T(2) dual-mode contrast agent for in vivo MRI with self-confirmation.