Nano assembly and encapsulation; a versatile platform for slowing the rotation of polyanionic Gd(3+) -based MRI contrast agents

Contrast Media Mol Imaging. 2016 Mar-Apr;11(2):154-9. doi: 10.1002/cmmi.1676. Epub 2015 Dec 28.

Abstract

Encapsulating discrete Gd(3+) chelates in nano-assembled capsules (NACs) is a simple and effective method of preparing an MRI contrast agent capable of delivering a large payload of high relaxivity imaging agent. The preparation of contrast agent containing NACs had previously focussed on preparations incorporating GdDOTP(5-) into the internal aggregate. In this report we demonstrate that other Gd(3+) chelates bearing overall charges as low as 2- can also be used to prepare NACs. This discovery opens up the possibility of using Gd(3+) chelates that have inner-sphere water molecules that could further increase the relaxivity enhancement associated with the long τR that arises from encapsulation. However, encapsulation of the q = 1 chelate GdDTPA(2-) did not give rise to a significant increase in relaxivity relative to encapsulation of the outer-sphere chelate GdTTHA(3-). This leads us to the conclusion that in the NAC interior proton transport is not mediated by movement of whole water molecules and the enhanced relaxivity of Gd(3+) chelate encapsulated within NACs arises primarily from second sphere effects.

Keywords: MRI contrast agent; large payload delivery; nano-encapsulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chelating Agents / chemistry
  • Contrast Media / chemistry*
  • Contrast Media / therapeutic use
  • Gadolinium DTPA / chemistry*
  • Gadolinium DTPA / therapeutic use
  • Humans
  • Magnetic Resonance Imaging*
  • Nanocapsules / chemistry*
  • Nanocapsules / therapeutic use
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use
  • Polyelectrolytes
  • Polymers / chemistry
  • Silicon Dioxide / chemistry
  • Water / chemistry

Substances

  • Chelating Agents
  • Contrast Media
  • Nanocapsules
  • Polyelectrolytes
  • Polymers
  • polyanions
  • Water
  • Silicon Dioxide
  • Gadolinium DTPA