High relaxivity MRI imaging reagents from bimodal star polymers

Abstract

Star polymer architectures were developed as multimodal imaging systems as fluorescence and magnetic resonance imaging (MRI) agents. Acrylate star polymers in hydrodynamic diameters of 10 ± 2 nm comprising fluorene derivatives as core units were modified with dopamine derivatives in adjustable quantities to chelate lanthanides such as Gd³⁺ and Eu³⁺. Ionic relaxivity values of 84 mM⁻¹s⁻¹ in an applied magnetic field of 0.5T at 37 °C confirmed the rapid water exchange of the highly hydrated star polymer. The utility is extended by the consecutive modification with allyl groups to perform thiol-ene reactions to conjugate thiol modified targeting units such as (cRGD) and dendritic molecular transporter as cell penetrating units. Cell uptake experiments in NIH 3T3 cells showed a rapid uptake of the star polymer independently of the presence of molecular transporter unit as it was detected through both the blue fluorescence of the fluorine core and the red fluorescence of the complexed Eu³⁺ to the linear polymer arms. In vivo mouse models confirmed the star polymer imaging reagent altered the image contrast significantly. In this work, we have adapted macromolecules as imaging agents for fluorescence microscopy and magnetic resonance imaging in conjunction with intracellular delivery and targeting.