title: Gadolinium-Loaded Poly(N-vinylcaprolactam) Nanogels: Synthesis, Characterization, and Application for Enhanced Tumor MR Imaging.
abstract: 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 r1relaxivity (6.38-7.10 mM-1s-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.
authors.affiliation: State Key Laboratory for Modification of Chemical Fiber and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University , Shanghai 201620, People's Republic of China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Sun
authors.affiliation: DWI-Leibniz-Institute for Interactive Materials e.V., Functional and Interactive Polymers, Institute for Technical and Macromolecular Chemistry, RWTH Aachen University , 52056 Aachen, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Thies
authors.affiliation: Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai 200072, People's Republic of China.
authors.forename: Jiulong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai 200072, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Radiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai 200072, People's Republic of China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Tang
authors.affiliation: State Key Laboratory for Modification of Chemical Fiber and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University , Shanghai 201620, People's Republic of China.
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.affiliation: DWI-Leibniz-Institute for Interactive Materials e.V., Functional and Interactive Polymers, Institute for Technical and Macromolecular Chemistry, RWTH Aachen University , 52056 Aachen, Germany.
authors.forename: Andrij
authors.initials: A
authors.lastname: Pich
authors.affiliation: State Key Laboratory for Modification of Chemical Fiber and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University , Shanghai 201620, People's Republic of China.
authors.forename: Xiangyang
authors.identifier: http://orcid.org/0000-0001-6785-6645
authors.initials: X
authors.lastname: Shi
mesh_terms: D002209:Caprolactam / Q000031:analogs & derivatives; D003287:Contrast Media; D005682:Gadolinium; D006801:Humans; D008279:Magnetic Resonance Imaging; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms; D011108:Polymers
chemical_list: D003287:Contrast Media; D011108:Polymers; C086861:poly-N-vinylcaprolactam; D002209:Caprolactam; D005682:Gadolinium
keywords: Gd-DOTA; MR imaging; nanogels; poly(N-vinylcaprolactam); tumors