Thermally-triggered 'off-on-off' response of gadolinium-hydrogel-lipid hybrid nanoparticles defines a customizable temperature window for non-invasive magnetic resonance imaging thermometry

Adam J. Shuhendler, Robert Staruch, Wendy Oakden, Claudia R. Gordijo, Andrew M. Rauth, Greg J. Stanisz, Rajiv Chopra, Xiao Yu Wu

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Abstract For effective and safe thermotherapy, real-time, accurate, three-dimensional tissue thermometry is required. Magnetic resonance imaging (MRI)-based thermometry in combination with current temperature responsive contrast agents only provides an 'off-on' signal at a certain temperature, not indicating temperature increases beyond the desired therapeutic levels. To overcome this limitation, a novel Gd-chelated hydrogel-lipid hybrid nanoparticle (HLN) formulation was developed that provides an 'off-on-off' signal defining a thermometric window for MR thermometry. Novel thermally responsive poly(N-isopropylacrylamide-co-acrylamide) (NIPAM-co-AM) hydrogel nanoparticles (< 15 nm) with bisallylamidodiethylenetriaminetriacetic acid, a novel crosslinker with Gd 3+ chelation functionality, were synthesized. The Gd-hydrogel nanoparticles were encapsulated in a solid lipid nanoparticle matrix that prevented T 1-weighted contrast signal enhancement. Melting of the matrix lipid freed the Gd-hydrogel nanoparticles into the bulk water and an 'off-on' contrast signal enhancement occurred. As the temperature was further increased to temperatures greater than, the volume phase transition temperature of the hydrogel nanoparticles, they collapsed and provided an 'on-off' signal diminution. Both the 'off-on' and the 'on-off' transition temperature could be tailored by changing the lipid matrix and altering the NIPAM/AM ratio in the hydrogel, respectively. This allowed MRI thermometry of different temperature windows using the Gd-HLN system.

Original languageEnglish (US)
Pages (from-to)478-484
Number of pages7
JournalJournal of Controlled Release
Volume157
Issue number3
DOIs
StatePublished - Feb 10 2012

Keywords

  • Hydrogel-lipid hybrid nanoparticles
  • Keywords
  • Magnetic resonance imaging
  • T1-weighted
  • Temperature responsive contrast agent
  • Thermometry
  • Thermotherapy

ASJC Scopus subject areas

  • Pharmaceutical Science

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