One-Pot Fabrication of Kinetically Inert Ultrasmall Manganese(II) Chelate-Backboned Polymer Contrast Agents for High-Performance Magnetic Resonance Imaging

Traditional macromolecules or nanoscale Mn²⁺ chelate-based magnetic resonance imaging (MRI) contrast agents (CAs) suffer from complicated and laborious synthesis processes, relatively low kinetic stability and <i>T</i>₁ relaxivity, limiting their clinical applications. Herein, we fabricated a series of kinetically inert Mn²⁺ chelate-backboned polymers, P(MnL-PEG), through a facile and one-pot polymerization process. Particularly, P(MnL-PEG)-3 demonstrates a significantly higher <i>T</i>₁ relaxivity of 23.9 Mn mM^-1 s^-1 at 1.5 T than that of previously reported small molecules and macromolecules or nanoscale Mn²⁺ chelate-based CAs. Due to its high <i>T</i>₁ relaxivity, extended blood circulation, hepatocyte-specific uptake, and kidneys metabolism, P(MnL-PEG)-3 presents significantly enhanced contrast in blood vessel, liver, and kidneys imaging compared to clinical Gd³⁺-based CAs (Gd-EOB-DTPA and Gd-DOTA) at a dosage of 0.05 mmol Mn/Gd kg^-1 BW, and can accurately diagnose orthotopic H22 liver tumors <i>in vivo</i> in animal models. We anticipate that this work will promote the development of clinically relevant MRI CAs.