We report the fabrication and characterization of thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) and their application to the dual imaging of
cancer in vivo. Unlike
dextran-coated cross-linked iron oxide nanoparticles, which are prepared by a chemical cross-linking method, TCL-SPION are prepared by a simple, thermal cross-linking method using a Si-
OH-containing copolymer. The copolymer, poly(3-(trimethoxysilyl)propyl methacrylate-r-PEG methyl ether methacrylate-r-N-acryloxysuccinimide), was synthesized by radical polymerization and used as a coating material for as-synthesized
magnetite (Fe3O4) SPION. The
polymer-coated SPION was further heated at 80 degrees C to induce cross-linking between the -Si(OH)3 groups in the
polymer chains, which finally generated TCL-SPION bearing a carboxyl group as a surface functional group. The particle size, surface charge, presence of
polymer-coating layers, and the extent of thermal cross-linking were characterized and confirmed by various measurements, including dynamic light scattering, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The carboxyl TCL-SPION was converted to
amine-modified TCL-SPION and then finally to
Cy5.5 dye-conjugated TCL-SPION for use in dual (magnetic resonance/optical) in vivo
cancer imaging. When the
Cy5.5 TCL-SPION was administered to
Lewis lung carcinoma tumor allograft mice by
intravenous injection, the
tumor was unambiguously detected in T2-weighted magnetic resonance images as a 68% signal drop as well as in optical fluorescence images within 4 h, indicating a high level of accumulation of the nanomagnets within the
tumor site. In addition, ex vivo fluorescence images of the harvested
tumor and other major organs further confirmed the highest accumulation of the
Cy5.5 TCL-SPION within the
tumor. It is noteworthy that, despite the fact that TCL-SPION does not bear any targeting
ligands on its surface, it was highly effective for
tumor detection in vivo by dual imaging.