title: 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.
abstract: 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.
authors: Cancer Institute, Japanese Foundation for Cancer Research, Ariake, Koto-ku, Tokyo 135-8550, Japan. sachiko.matsumura@jfcr.or.jp
authors: Sachiko
authors: S
authors: Matsumura
authors: Ichio
authors: I
authors: Aoki
authors: Tsuneo
authors: T
authors: Saga
authors: Kiyotaka
authors: K
authors: Shiba
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry; D005293:Ferritins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008279:Magnetic Resonance Imaging; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D013499:Surface Properties
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D009363:Neoplasm Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D011092:Polyethylene Glycols; C092844:ferric oxyhydroxide; D005293:Ferritins; D020778:Matrix Metalloproteinase 2