Gadolinium-Loaded Poly(<i>N</i>‑vinylcaprolactam) Nanogels: Synthesis, Characterization, and Application for Enhanced Tumor MR Imaging

We report the synthesis of poly­(<i>N</i>-vinylcaprolactam) nanogels (PVCL NGs) loaded with gadolinium (Gd) for tumor MR imaging applications. The PVCL NGs were synthesized via precipitation polymerization using the monomer <i>N</i>-vinylcaprolactam (VCL), the comonomer acrylic acid (AAc), and the degradable cross-linker 3,9-divinyl-2,4,8,10-tetraoxaspiro-[5,5]-undecane (VOU) in aqueous solution, followed by covalently binding with 2,2′,2″-(10-(4-((2-aminoethyl)­amino)-1-carboxy-4-oxobutyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl) triacetic acid (NH₂-DOTA-GA)/Gd complexes. We show that the formed Gd-loaded PVCL NGs (PVCL-Gd NGs) having a size of 180.67 ± 11.04 nm are water dispersible, colloidally stable, uniform in size distribution, and noncytotoxic in a range of the studied concentrations. The PVCL-Gd NGs also display a r₁ relaxivity (6.38–7.10 mM^–1 s^–1), which is much higher than the clinically used Gd chelates. These properties afforded the use of the PVCL-Gd NGs as an effective positive contrast agent for enhanced MR imaging of cancer cells in vitro as well as a subcutaneous tumor model in vivo. Our study suggests that the developed PVCL-Gd NGs could be applied as a promising contrast agent for <i>T</i>₁-weighted MR imaging of diverse biosystems