Protease-triggered unveiling of bioactive nanoparticles

A general strategy for reversibly veiling bioactive domains on nanoparticles using sterically protective polymers was reported. The nanoparticles used were synthesized, cross-linked, animated, and labeled with a near-infrared fluorophore. Two species, a cell internalization domain and a removable hydrophilic polymer, consisting of a linear PEG tethered by an MMP-2 cleavable substrate, were conjugated onto the surface of a magnetofluorescent dextran-coated iron oxide nanoparticle. Particles with lower domain densities were taken up minimally by cells in both he veiled and unveiled state, while particles with higher domain densities were taken up by cells even with the intact polymer coating. A T2 mapping sequence was used to detect T2 changes in cells that had been incubated with veiled and unveiled nanoparticles for 5h. The results from fluorescence molecular tomography show that cleavable particles do not accumulate more than non-cleavable controls in tumor regions.