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

Abstract

Star polymers with a branched core and hydrophilic arms were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization as pH-responsive ¹⁹F magnetic resonance imaging (MRI) agents. The branched core consists of 2,2,2-trifluoroethyl acrylate (TFEA, providing ¹⁹F 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. ¹⁹F nuclear magnetic resonance (¹⁹F NMR) revealed that the ¹⁹F signal intensity and spin–spin relaxation time (T₂) were significantly dependent on the pH of polymer solution, while the ¹⁹F spin-lattice (T₁) relaxation time remained constantly low at ∼450 ms upon increasing the pH above the pK_a of the DMAEMA groups. A dramatic change in ¹⁹F MRI imaging intensity was observed on passing from an alkaline to an acidic environment. These results indicate that these ¹⁹F detectable and pH-sensitive star polymer nanoparticles are promising as ¹⁹F MRI “smart” contrast agents for selective imaging.