A Tumor-Environment-Responsive Nanocarrier That Evolves Its Surface Properties upon Sensing Matrix Metalloproteinase-2 and Initiates Agglomeration to Enhance T2 Relaxivity for Magnetic Resonance Imaging

We designed and synthesized a modified ferritin as a tumor-environment-responsive nanocarrier. We found that this nanocarrier could evolve its surface properties upon sensing a tumor-associated protease, matrix metalloproteinase-2 (MMP-2), which initiated agglomeration, resulting in the enhancement of T-2 relaxivity for magnetic resonance imaging (MRI). The designed ferritin contained a triad of modifiers composed of (i) a sensing segment (substrate peptide of MMP-2), (ii) hydrophobic segments and (iii) a hydrophilic segment: of polyethylene glycol (PEG). The hydrophilic segment ensured the particles' monodispersibility in aqueous conditions. In the presence of MMP-2 activity, the sensing segment was cleaved by the enzyme and its submerged hydrophobic segments were exposed on the surface, resulting in the initiation of aggregation. Because ferritin contains ferrihydrite in its inner space, this multimerization resulted in the enhancement of T-2 relaxivity, suggesting that this nanocarrier may be useful as a contrast agent in MRI