title: Thermally-triggered 'off-on-off' response of gadolinium-hydrogel-lipid hybrid nanoparticles defines a customizable temperature window for non-invasive magnetic resonance imaging thermometry.
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.
authors.affiliation: Department of Pharmaceutical Sciences, Leslie L. Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 3M2. adam.shuhendler@utoronto.ca
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Shuhendler
authors.forename: Robert
authors.initials: R
authors.lastname: Staruch
authors.forename: Wendy
authors.initials: W
authors.lastname: Oakden
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Gordijo
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Rauth
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Stanisz
authors.forename: Rajiv
authors.initials: R
authors.lastname: Chopra
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Wu
mesh_terms: D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry; D000180:Acrylic Resins / Q000737:chemistry; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006358:Hot Temperature; D020100:Hydrogels / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000085:Acetates; D000180:Acrylic Resins; D002614:Chelating Agents; D003287:Contrast Media; D004337:Drug Carriers; D020100:Hydrogels; C469412:poly(N-isopropylacrylamide-co-acrylamide); D011092:Polyethylene Glycols; C009314:polyethylene glycol monostearate; D005682:Gadolinium