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

• Published in: ACS applied materials & interfaces Vol. 9; no. 4; pp. 3411 - 3418
• Main Authors: Sun, Wenjie, Thies, Sabrina, Zhang, Jiulong, Peng, Chen, Tang, Guangyu, Shen, Mingwu, Pich, Andrij, Shi, Xiangyang
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.02.2017
• Subjects: Caprolactam - analogs & derivatives; Contrast Media; Gadolinium; Humans; Magnetic Resonance Imaging; Nanoparticles - chemistry; Neoplasms; Polymers; poly(N-vinylcaprolactam); Gd-DOTA; tumors; MR imaging; nanogels
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.6b14219

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-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 T 1-weighted MR imaging of diverse biosystems.