Self-assembled double hydrophilic block copolymers mixed with paramagnetic lanthanides for use as PARACEST MRI agents

Diba Allameh Zadeh1 , Cabell B. Eades2  , Brent Summerlin2  , Daniel R. Talham1

Department of Chemistry, University of Florida, Gainesville, Florida 32611, USA

A groundbreaking approach has been developed for designing responsive paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance imaging (MRI) agents, utilizing hybrid polyion complexes (HPICs) as nanoparticle-based MRI contrast agents. These HPICs are formed by adding metal ions to a solution of a double-hydrophilic block copolymer, leading to the spontaneous formation of highly uniform nano-objects. In this study, an effective strategy employing a mixture of metal ions was proposed. One metal ion was chosen for its ability to ensure high chemical stability of the nano-objects, while the other was selected to impart the desired magnetic property to the nanostructure. The copolymer of choice, poly(oligoethylene glycol methacrylate-b-methaacrylic acid), was combined with calcium ions () to reinforce the stability of the HPIC architecture. Lanthanide ions, commonly used in contrast agents for proton-magnetic resonance imaging, were mixed with the calcium ions and the copolymer, resulting in nano-objects with an average radius of approximately 40-50 nm. Chemical exchange saturation transfer (CEST) measurements showed a significant decrease in total bulk water signal intensity (Mz/M0), with CEST peaks distinctly shifted away from the bulk water signal in the range of approximately ~3-8 ppm, even at relatively low concentrations of lanthanide ions. This effect was attributed to a two-pool model, wherein the lanthanide-shifted protons at the core of the HPICs rapidly exchanged with the surrounding water protons in the bulk water pool. The resulting nano-objects can be excellent choice for contrast agents with good biocompatibility. Furthermore, the size and shape of these paramagnetic HPICs can be modified, making them a promising candidate for MRI contrast agents.