Uniform and Length-Tunable, Paramagnetic Self-Assembled Nitroxide-Based Nanofibers for Magnetic Resonance Imaging

Abstract

Magnetic resonance imaging (MRI) is a widely used non-invasive medical imaging tool. Nanoparticle-based MRI contrast agents have received considerable attention due to their high loading capability for magnetic species, enhanced accumulation in lesions, and versatile surface functionalization. Anisotropic nanoparticles such as nanofibers can exhibit significant advantages over their well-explored spherical counterparts in terms of their pharmacokinetic and biodistribution profiles. Herein, we report the retrosynthetic design, synthesis, and characterization of uniform and length-tunable paramagnetic core-shell nanofibers for MRI through the use of the seeded-growth “living” crystallization-driven self-assembly (CDSA) approach. Triblock copolymer (TriBCP) precursors with a crystallizable polycarbonate core-forming segment, a nitroxide-bearing central region, and a hydrophilic poly(ethylene glycol) (PEG) terminal corona-forming segment were prepared via sequential living organocatalytic ring-opening polymerization (ROP). Low dispersity nanofibers of length ca. 80 nm relevant for biomedical applications were prepared for detailed studies by living CDSA and these possessed an average number of nitroxides per nanofiber of >8000. Subsequent evaluation of the water-proton relaxivities demonstrated that tuning the hydrophilicity of the central segment in the TriBCP allowed access to nanofibers with impressive performance compared to most existing polymer-based nitroxide-based contrast agents. As a result of their 1D morphology, the synthetic nanofibers therefore represent promising organic radical contrast agents (ORCAs) for MRI applications.