Gadolinium-functionalized nanoparticles for application as magnetic resonance imaging contrast agents: via polymerization-induced self-assembly

Lars Esser, Nghia P. Truong, Bunyamin Karagoz, Bradford A. Moffat, Cyrille Boyer, John F. Quinn, Michael R. Whittaker, Thomas P. Davis

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Polymerization-induced self-assembly (PISA) is an easily applied synthetic technique for the preparation of polymer nanoparticles with various shapes and at high concentrations. Although PISA has been applied to prepare nanoparticles for a variety of different applications, to date there have been no attempts to employ nanoparticles prepared via PISA as a novel platform from which to prepare positive contrast agents for magnetic resonance imaging (MRI). To this end, here we report an efficient synthesis of surface-functional polymer-based nanoparticles with tunable size and morphology (micelles, filomicelles and vesicles) via PISA, their post-synthetic functionalisation and an initial investigation into their use as a positive MRI contrast agent. A short functional block of poly(glycidyl methacrylate) was prepared using reversible addition-fragmentation chain transfer (RAFT) polymerization, and this was chain extended with oligo(ethylene glycol) methyl ether methacrylate to create a novel macromolecular chain transfer agent for PISA. A library of surface-functional self-assembled nanoparticles with different shapes was then synthesized, and the versatility of the glycidyl methacrylate units for post-synthetic surface functionalization was demonstrated by ring opening the epoxide with a primary thiol, a primary amine and sodium azide. The resulting azide functional materials could be further modified via copper-catalysed azide-alkyne cycloaddition. The epoxide groups were also exploited to conjugate Gd-DOTA to the polymeric nanoparticles and the application of the diverse polymeric nanoparticles for T1-weighted MRI was investigated, with the filomicelle emerging as a promising candidate due to both a good gadolinium-labelling efficiency and a high T1 relaxivity. Given that filomicelles typically exhibit enhanced blood circulation times, the gadolinium-labelled filomicelles could have potential applications as a blood pool agent for magnetic resonance angiography, and in cancer diagnostics/theranostics.

Original languageEnglish
Pages (from-to)7325-7337
Number of pages13
JournalPolymer Chemistry
Volume7
Issue number47
DOIs
Publication statusPublished - 21 Dec 2016

Cite this

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title = "Gadolinium-functionalized nanoparticles for application as magnetic resonance imaging contrast agents: via polymerization-induced self-assembly",
abstract = "Polymerization-induced self-assembly (PISA) is an easily applied synthetic technique for the preparation of polymer nanoparticles with various shapes and at high concentrations. Although PISA has been applied to prepare nanoparticles for a variety of different applications, to date there have been no attempts to employ nanoparticles prepared via PISA as a novel platform from which to prepare positive contrast agents for magnetic resonance imaging (MRI). To this end, here we report an efficient synthesis of surface-functional polymer-based nanoparticles with tunable size and morphology (micelles, filomicelles and vesicles) via PISA, their post-synthetic functionalisation and an initial investigation into their use as a positive MRI contrast agent. A short functional block of poly(glycidyl methacrylate) was prepared using reversible addition-fragmentation chain transfer (RAFT) polymerization, and this was chain extended with oligo(ethylene glycol) methyl ether methacrylate to create a novel macromolecular chain transfer agent for PISA. A library of surface-functional self-assembled nanoparticles with different shapes was then synthesized, and the versatility of the glycidyl methacrylate units for post-synthetic surface functionalization was demonstrated by ring opening the epoxide with a primary thiol, a primary amine and sodium azide. The resulting azide functional materials could be further modified via copper-catalysed azide-alkyne cycloaddition. The epoxide groups were also exploited to conjugate Gd-DOTA to the polymeric nanoparticles and the application of the diverse polymeric nanoparticles for T1-weighted MRI was investigated, with the filomicelle emerging as a promising candidate due to both a good gadolinium-labelling efficiency and a high T1 relaxivity. Given that filomicelles typically exhibit enhanced blood circulation times, the gadolinium-labelled filomicelles could have potential applications as a blood pool agent for magnetic resonance angiography, and in cancer diagnostics/theranostics.",
author = "Lars Esser and Truong, {Nghia P.} and Bunyamin Karagoz and Moffat, {Bradford A.} and Cyrille Boyer and Quinn, {John F.} and Whittaker, {Michael R.} and Davis, {Thomas P.}",
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Gadolinium-functionalized nanoparticles for application as magnetic resonance imaging contrast agents : via polymerization-induced self-assembly. / Esser, Lars; Truong, Nghia P.; Karagoz, Bunyamin; Moffat, Bradford A.; Boyer, Cyrille; Quinn, John F.; Whittaker, Michael R.; Davis, Thomas P.

In: Polymer Chemistry, Vol. 7, No. 47, 21.12.2016, p. 7325-7337.

Research output: Contribution to journalArticleResearchpeer-review

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T2 - via polymerization-induced self-assembly

AU - Esser, Lars

AU - Truong, Nghia P.

AU - Karagoz, Bunyamin

AU - Moffat, Bradford A.

AU - Boyer, Cyrille

AU - Quinn, John F.

AU - Whittaker, Michael R.

AU - Davis, Thomas P.

PY - 2016/12/21

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