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

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• 作者：Wenjie Sun ; Sabrina Thies ; Jiulong Zhang ; Chen Peng ; Guangyu Tang ; Mingwu Shen ; Andrij Pich ; Xiangyang Shi
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2017
• 出版时间：February 1, 2017
• 年：2017
• 卷：9
• 期：4
• 页码：3411-3418
• 全文大小：492K
• ISSN：1944-8252

文摘

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 T₁-weighted MR imaging of diverse biosystems.