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

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.