TY - JOUR
T1 - Multifunctional polymeric scaffolds for enhancement of PARACEST contrast sensitivity and performance
T2 - Effects of random copolymer variations
AU - Wu, Yunkou
AU - Zhao, Piyu
AU - Kiefer, Garry E.
AU - Sherry, A. Dean
PY - 2010/8/24
Y1 - 2010/8/24
N2 - A DOTA (1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴- tetraacetic acid) tetraamide ligand having a single acrylamide side chain (M1) was copolymerized with either 2-methylacrylic acid (MAA), 2-(acryloylamino)-2- methyl-1-propanesulfonic acid (AMPS), or N-isopropylacrylamide (NIPAM) to create a series of linear random copolymers using classical free radical chain polymerization chemistry. The metal ion binding properties of hydrolyzed M1 were investigated by pH potentiometry and the europium(III) complexes of the resulting heteropolymers were evaluated as PARACEST imaging agents. All polymeric agents were found to possess similar intermediate-to-slow water exchange and CEST characteristics as the parent EuDOTA-tetraamide monomer. Consistent with basic multiplexing principles, the highest molecular weight polymer, Eu-DMAA 3.1, also showed the highest CEST sensitivity with a detection limit of 20 ± 2 μM. The second arylamide component gave polymers with widely different chemical characteristics and CEST properties. In particular, the Eu-DNIPAM 4.0 and Eu-DMAA 4.1 polymers displayed different solubility characteristics as a function of pH or temperature which, in turn, affected the water exchange and CEST properties of the corresponding agents. It was concluded that introduction of hydrophobic groups into the polymer backbone reduces solvent accessibility to the Eu3+ component, effectively slowing water exchange between the inner-sphere water coordination position at each Eu3+ center with bulk water. The CEST properties of the heteropolymers when dissolved in plasma suggest that the more hydrophobic characteristics of these polymers could be advantageous for in vivo applications.
AB - A DOTA (1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴- tetraacetic acid) tetraamide ligand having a single acrylamide side chain (M1) was copolymerized with either 2-methylacrylic acid (MAA), 2-(acryloylamino)-2- methyl-1-propanesulfonic acid (AMPS), or N-isopropylacrylamide (NIPAM) to create a series of linear random copolymers using classical free radical chain polymerization chemistry. The metal ion binding properties of hydrolyzed M1 were investigated by pH potentiometry and the europium(III) complexes of the resulting heteropolymers were evaluated as PARACEST imaging agents. All polymeric agents were found to possess similar intermediate-to-slow water exchange and CEST characteristics as the parent EuDOTA-tetraamide monomer. Consistent with basic multiplexing principles, the highest molecular weight polymer, Eu-DMAA 3.1, also showed the highest CEST sensitivity with a detection limit of 20 ± 2 μM. The second arylamide component gave polymers with widely different chemical characteristics and CEST properties. In particular, the Eu-DNIPAM 4.0 and Eu-DMAA 4.1 polymers displayed different solubility characteristics as a function of pH or temperature which, in turn, affected the water exchange and CEST properties of the corresponding agents. It was concluded that introduction of hydrophobic groups into the polymer backbone reduces solvent accessibility to the Eu3+ component, effectively slowing water exchange between the inner-sphere water coordination position at each Eu3+ center with bulk water. The CEST properties of the heteropolymers when dissolved in plasma suggest that the more hydrophobic characteristics of these polymers could be advantageous for in vivo applications.
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U2 - 10.1021/ma100776d
DO - 10.1021/ma100776d
M3 - Article
C2 - 20838469
AN - SCOPUS:77955729147
SN - 0024-9297
VL - 43
SP - 6616
EP - 6624
JO - Macromolecules
JF - Macromolecules
IS - 16
ER -