Hybrid Polymeric Nanostructures Stabilized by Zirconium and Gadolinium Ions for Use as Magnetic Resonance Imaging Contrast Agents

Nanostructures called hybrid polyion complexes (HPICs) are formed by adding metal ions to a solution of a double-hydrophilic block copolymer, leading to the spontaneous formation of highly monodisperse nano-objects. In this paper, we propose a simple strategy based on a mixture of metal ions: one chosen to achieve high chemical stability of the nano-objects and the second included to provide a desired property to the nanostructure. Using poly­(ethylene oxide)-b-poly­(acrylic acid) as the copolymer, the zirconium ion, added as ZrO²⁺, was selected to ensure strong interactions with the polymers to reinforce the stability of the HPIC architecture. The zirconyl ions were combined with lanthanide ions, which are often used in contrast agents for proton-magnetic resonance imaging. Mixing the two metal ions with the copolymer led to nano-objects with an average radius of ca 11–16 nm. Increasing the zirconyl mole fraction inside the HPICs leads to excellent chemical stability of the nano-objects. Unexpectedly, when paired with Gd³⁺, the mixed metal HPIC exhibits greatly enhanced magnetic relaxivity relatively to the single-ion Gd³⁺ HPIC, when the zirconyl mole fraction increases. This behavior was further studied by nuclear magnetic relaxation dispersion. The resulting nano-objects are excellent contrast agents with a good biocompatibility. In addition, there is significant potential for extending the mixed metal HPIC platform to other areas of study.