Single-chain polyacrylic nanoparticles with multiple Gd(iii) centres as potential MRI contrast agents

Abstract

One of the approaches for obtaining magnetic resonance imaging (MRI) contrast agents with enhanced relaxivity is to construct macromolecular architectures with multiple Gd(III) centres. In some cases, simple grafting of Gd(III) chelates into polymeric backbones does not result in an increased relaxivity, due to high internal flexibility or a non-rigid attachment of the chelate to the macromolecule. Here we describe a new method for incorporating Gd(III) ions into a polymer in a rigid manner by complexing them into the cross-linker. Thus, acrylic copolymer 4 (M_w = 50 kDa) was forced to collapse intramolecularly by means of the bifunctional cross-linker 6 that had a diethylenetriaminepentaacetic acid (DTPA) group incorporated into it. This results in the formation of water-soluble polymeric nanoparticles (PNPs) 8, which were subsequently loaded with Gd(III) ions to give paramagnetic PNPs 9, with a mean particle size of 1.5 nm. The r₁ relaxivity value for PNPs 9 on a per Gd basis was 6.78 mM⁻¹s⁻¹, which represents a 2-fold increase over Magnevist^® and a 4-fold increase compared to its monometallic counterpart, the Gd-loaded cross-linker 7.