title: Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging.
abstract: Theranostic nano-polyplexes containing gene and imaging agents hold a great promise for tumor diagnosis and therapy. In this work, we develop a group of new gadolinium (Gd)-chelated cationic poly(urethane amide)s for gene delivery and T1-weighted magnetic resonance (MR) imaging. Cationic poly(urethane amide)s (denoted as CPUAs) having multiple disulfide bonds, urethane and amide linkages were synthesized by stepwise polycondensation reaction between 1,4-bis(3-aminopropyl)piperazine and a mixture of di(4-nitrophenyl)-2, 2'-dithiodiethanocarbonate (DTDE-PNC) and diethylenetriaminepentaacetic acid (DTPA) dianhydride at varied molar ratios. Then, Gd-chelated CPUAs (denoted as GdCPUAs) were produced by chelating Gd(III) ions with DTPA residues of CPUAs. These GdCPUAs could condense gene into nanosized and positively-charged polyplexes in a physiological condition and, however, liberated gene in an intracellular reductive environment. In vitro transfection experiments revealed that the GdCPUA at a DTDE-PNC/DTPA residue molar ratio of 85/15 induced the highest transfection efficiency in different cancer cells. This efficiency was higher than that yielded with 25kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxicity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T1-weighted magnetic resonance imaging. The results of this work indicate that biodegradable Gd-chelated cationic poly(urethane amide) copolymers have high potential for tumor theranostics.
authors.affiliation: Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, PR China.
authors.forename: Gangmin
authors.initials: G
authors.lastname: Wang
authors.affiliation: The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Shi
authors.affiliation: Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Shao
authors.affiliation: The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China.
authors.forename: Donglu
authors.initials: D
authors.lastname: Shi
authors.affiliation: Institute of Nano and Biopolymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China. Electronic address: chaolin@tongji.edu.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China. Electronic address: tjpjwang@sina.com.
authors.forename: Peijun
authors.initials: P
authors.lastname: Wang
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D002412:Cations; D003287:Contrast Media; D011108:Polymers; D034741:RNA, Small Interfering; D005682:Gadolinium
keywords: Disulfide; Gene delivery; Imaging; Poly(urethane amide); Theranostics