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 T2 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\u27 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 T2 relaxivity, suggesting that this nanocarrier may be useful as a contrast agent in MRI