Phosphonic Acid-Enriched Nanogels as High Relaxivity Platforms for Enhanced Magnetic Resonance Imaging and Drug Delivery

Clinically small-molecule magnetic resonance imaging (MRI) contrast agents face limitations due to safety concerns, low relaxivity, narrow imaging windows, and restricted targeting capabilities. This study synthesized biocompatible nanogels via the polymerization of N-vinyl caprolactam and vinyl phosphonic acid. The nanogels containing phosphonic acid groups could tightly bind with Mn²⁺, which could improve the biosafety by preventing the release of free Mn²⁺. Meanwhile, the strong ligand effect improved the longitudinal relaxivity of encapsulated Mn²⁺ to 29.8 mM⁻¹s⁻¹, which was roughly 3.5 times, 10.6 times, and 6.6 times higher than that of manganese chloride (MnCl₂), mangafodipir (MnDPDP) and gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA), respectively. These nanogels exhibited the capability of targeting bone metastases and bone tissues in vivo owing to the phosphonic acid groups. Moreover, these nanogels-based contrast agents prolonged the effective imaging window due to the increased circulation time. They also exhibited a loading capacity for clinical hydrophobic drugs, such as atovaquone (ATO), thereby potentially improving the pharmacokinetics. This work highlights the prospect of poly(vinyl phosphonic acid) based nanogels as multifunctional nanoplatforms for diagnostic and therapeutic applications.