TY - JOUR
T1 - Thermally-triggered 'off-on-off' response of gadolinium-hydrogel-lipid hybrid nanoparticles defines a customizable temperature window for non-invasive magnetic resonance imaging thermometry
AU - Shuhendler, Adam J.
AU - Staruch, Robert
AU - Oakden, Wendy
AU - Gordijo, Claudia R.
AU - Rauth, Andrew M.
AU - Stanisz, Greg J.
AU - Chopra, Rajiv
AU - Wu, Xiao Yu
N1 - Funding Information:
This work was partly supported by a Discovery Grant from the National Science and Engineering Research Council of Canada to X.Y. Wu. Scholarships to AJS are provided by the National Science and Engineering Research Council of Canada, and the University of Toronto Ben Cohen Fund are also acknowledged.
PY - 2012/2/10
Y1 - 2012/2/10
N2 - 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.
AB - 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.
KW - Hydrogel-lipid hybrid nanoparticles
KW - Keywords
KW - Magnetic resonance imaging
KW - T1-weighted
KW - Temperature responsive contrast agent
KW - Thermometry
KW - Thermotherapy
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U2 - 10.1016/j.jconrel.2011.09.061
DO - 10.1016/j.jconrel.2011.09.061
M3 - Article
C2 - 21939700
AN - SCOPUS:84857363962
SN - 0168-3659
VL - 157
SP - 478
EP - 484
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 3
ER -