Release activation of iron oxide nanoparticles: (REACTION) a novel environmentally sensitive MRI paradigm.

Smart contrast agents for MRI-based cell tracking would enable the use of MRI methodologies to not only detect the location of cells but also gene expression. Here, we report on a new enzyme/contrast agent paradigm which involves the enzymatic degradation of the polymer coating of magnetic nanoparticles to release encapsulated magnetic cores. Cells were labeled with particles coated with a polymer, which is cleavable by a specific enzyme. This coat restricts the approach of water to the particle, preventing the magnetic core from efficiently relaxing protons. The reactive enzyme was delivered to cells and changes in cellular T(2) and T(2)* relaxation times of ~ 35% and ~ 50% were achieved in vitro. Large enhancements of dark contrast volume (240%) and contrast-to-noise ratio (48%) within the contrast regions were measured, in vivo, for cells co-labeled with enzyme and particles. These results warrant exploration of genetic avenues toward achieving release activation of iron oxide nanoparticles.