期刊
JOURNAL OF CONTROLLED RELEASE
卷 157, 期 3, 页码 478-484出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2011.09.061
关键词
Magnetic resonance imaging; Thermometry; Hydrogel-lipid hybrid nanoparticles; T1-weighted; Temperature responsive contrast agent; Thermotherapy
资金
- National Science and Engineering Research Council of Canada
- University of Toronto
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 Gd3+ 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. (C) 2011 Elsevier B. V. All rights reserved.
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