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Silica coated, PEI and citric acid hybrid superparamagnetic magnetite nanocrystal clusters (SMNC) were synthesized using either a mini-emulsion/sol-gel method or a polyol technique. After careful characterization of the size, structure, composition, and magnetic properties, the as-synthesized SMNC were used for cell labeling while the MR detection sensitivity of cells labeled with silica SMNC was performed with a 3 T whole body MR scanner. TEM investigations revealed that the sizes of the SMNC were about 200 nm and the SMNC mainly consisted of magnetite nanoparticles imbedded in a PEI, citric acid or polystyrene scaffold. Silica and citric acid SMNC were highly negatively charged and PEI SMNC were positively charged. Relaxometry measurements revealed that these SMNC possessed a very high MR sensitivity (silica SMNC: r(2) = 299 s(-1) mM(-1), PEI SMNC: r(2) = 124 s(-1) mM(-1)), especially for the citric acid SMNC (r(2) = 360 s(-1) mM(-1)). Furthermore, when used for cell (RAW264.7 cells) labeling, the SMNC had no adverse effect on cell viability, and the cell uptake of the SMNC show a dose- and time-dependent feature. MR imaging of cells labeled with silica SMNC indicated that cells with a concentration as low as 10 x 10(3) cells ml(-1) could be detected with a 3 T MRI scanner. Our study demonstrated that superparamagnetic magnetite nanocrystal clusters are a sensitive tool for cell imaging.

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