Controlled intracellular self-assembly of gadolinium nanoparticles as smart molecular MR contrast agents

Sci Rep. 2013:3:1024. doi: 10.1038/srep01024. Epub 2013 Jan 3.

Abstract

Herein we developed a new "smart" Gd-based MR contrast agent (i.e., 1) which is susceptive to furin, a protease overexpressed in tumor. Under the action of furin, 1 condenses to form dimers (1-Ds) and the latter self-assemble into gadolinium nanparticles (Gd-NPs). Relaxivity of 1-D is more than 2 folds of those of 1 and magnevist at 1.5 T, and 1.4 folds of that of 1 at 3 T. Intracellular condensation of 1 in furin-overexpressed MDA-MB-468 cells was proven with direct two-photon laser microscopy (TPLM) fluorescence imaging of the cells incubated with the europium analog of 1 (i.e., 2). Intracellular Gd-NPs of 1 were uncovered and characterized for the first time. MRI of MDA-MB-468 tumors showed that 1 has enhanced MR contrast within the tumors than that of its scrambled control 1-Scr.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Contrast Media / chemical synthesis
  • Contrast Media / chemistry*
  • Dimerization
  • Europium / chemistry
  • Furin / metabolism
  • Gadolinium / chemistry*
  • Humans
  • Magnetic Resonance Imaging
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Mice
  • Mice, Nude
  • Microscopy, Confocal
  • Neoplasms / diagnostic imaging
  • Radiography
  • Transplantation, Heterologous

Substances

  • Contrast Media
  • Europium
  • Gadolinium
  • Furin