Mussel-Inspired Multidentate Block Copolymer to Stabilize Ultrasmall Superparamagnetic Fe3O4 for Magnetic Resonance Imaging Contrast Enhancement and Excellent Colloidal Stability

Colloidal ultrasmall superparamagnetic iron oxide nanopartides (USNPs) with better control of their surface chemistry have been considered as a biocompatible alternative to clinically used gadolinium-based contrast agents for in vivo bright magnetic resonance imaging (MRI). Herein, we report a versatile mussel-inspired multidentate block copolymer strategy that allows for the stabilization of USNPs as promising MRI contrast agents with excellent colloidal stability. A well-controlled multidentate block copolymer with pendant multiple catechol groups (Cat-MDBC) is synthesized by a combination of controlled radical polymerization and postmodification methods. The Cat-MDBC proves to be effective to strongly anchor to USNP surfaces as well as provide optimal hydrophilic surfaces, thus enabling the fabrication of aqueous Cat-MDBC/USNP colloids at single layers with a diameter of approximate to 20 nm through a biphasic ligand exchange process. They exhibit excellent colloidal stability in broad pH range and physiological conditions; no significant protein adsorption; and great magnetic properties including relaxivity and in vitro MRI. Further comparison of Cat-MDBC with its corresponding catechol-based multidentate random copolymer suggests the importance of the architecture of multidentate polymeric ligands for USNP-based MRI diagnosis.