pH-responsive star polymer nanoparticles: potential 19F MRI contrast agents for tumour-selective imaging

Star polymers with a branched core and hydrophilic arms were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization as pH-responsive F-19 magnetic resonance imaging (MRI) agents. The branched core consists of 2,2,2-trifluoroethyl acrylate (TFEA, providing F-19 MRI signal) and 2-(dimethylamino)ethyl methacrylate (DMAEMA, offering pH-responsive properties). The arms are comprised of poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) brushes that form hydrophilic and biocompatible shells around the cores. The structure and composition of the star polymers were characterised in detail. Nanoparticles were fabricated by direct dissolution of the star polymers in aqueous solution. F-19 nuclear magnetic resonance (F-19 NMR) revealed that the F-19 signal intensity and spin-spin relaxation time (T-2) were significantly dependent on the pH of polymer solution, while the F-19 spin-lattice (T-1) relaxation time remained constantly low at similar to 450 ms upon increasing the pH above the pK(a) of the DMAEMA groups. A dramatic change in F-19 MRI imaging intensity was observed on passing from an alkaline to an acidic environment. These results indicate that these F-19 detectable and pH-sensitive star polymer nanoparticles are promising as F-19 MRI "smart" contrast agents for selective imaging.