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

We report the synthesis of poly(N-vinylcaprolactam) nanogels (PVCL NGs) loaded with gadolinium (Gd) for tumor MR imaging applications. The PVCL NGs were synthesized via precipitation polymerization using the monomer N-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-amino ethyl) amin o)-1-carb oxy-4-oxobutyl) -1,4,7,104 etraazacycl o do de cane -1,4,7triyl) triacetic acid (NH2-DOTA-GA)/Gd complexes. We show that the formed Gdloaded 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-'), 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 contrast agent for T-1-weighted MR imaging of diverse biosystems. could be applied as a promising contrast agent for T-1-weighted MR imaging of diverse biosystems.