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首页> 外文期刊>Materials science & engineering >Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging
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Biodegradable gadolinium-chelated cationic poly(urethane amide) copolymers for gene transfection and magnetic resonance imaging

机译：可生物降解的-螯合阳离子聚（氨基甲酸酯酰胺）共聚物，用于基因转染和磁共振成像

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摘要

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 T,-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 polycon-densation 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 25 kDa branched polyethylenimine as a positive control. GdCPUAs and their polyplexes exhibited low cytotoxic-ity when an optimal transfection activity was detected. Moreover, GdCPUAs may serve as contrast agents for T_1-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.
机译：含基因和显像剂的治疗性纳米复合物在肿瘤的诊断和治疗方面具有广阔的前景。在这项工作中，我们开发了一组新的g（Gd）螯合的阳离子聚（氨基甲酸酯酰胺），用于基因传递和T加权磁共振（MR）成像。通过1,4-双（3-氨基丙基）哌嗪与二（4-硝基苯基）混合物的逐步缩聚反应合成了具有多个二硫键，氨基甲酸酯和酰胺键的阳离子聚（氨基甲酸酯酰胺）（称为CPUA） ）-2，2'-二硫代二硫代碳酸酯（DTDE-PNC）和二亚乙基三胺五乙酸（DTPA）二酐的摩尔比不同。然后，通过将Gd（Ⅲ）离子与CPUA的DTPA残基螯合来制备Gd螯合的CPUA（称为GdCPUA）。这些GdCPUA可以在生理条件下将基因浓缩为纳米级且带正电荷的多链体，但是在细胞内还原性环境中可以释放基因。体外转染实验表明，DTDE-PNC / DTPA残留摩尔比为85/15的GdCPUA在不同癌细胞中诱导了最高的转染效率。该效率高于使用25 kDa支链聚乙烯亚胺作为阳性对照的效率。当检测到最佳转染活性时，GdCPUA及其多聚体表现出低细胞毒性。此外，GdCPUA可以用作T_1加权磁共振成像的造影剂。这项工作的结果表明，可生物降解的Gd螯合阳离子聚（氨基甲酸酯酰胺）共聚物对肿瘤治疗具有很高的潜力。

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  • 来源
    《Materials science & engineering》 |2016年第8期|181-187|共7页
  • 作者

    Xiaolong Gao; Gangmin Wang; Ting Shi; Zhihong Shao; Peng Zhao; Donglu Shi; Jie Ren; Chao Lin; Peijun Wang;

  • 作者单位

    Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China;

    Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, PR China;

    The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China;

    Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China;

    The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China;

    The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China;

    Institute of Nano and Biopolymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, PR China;

    The Institute for Translational Nanomedicine, Shanghai East Hospital, Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Shanghai 200092, PR China;

    Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, PR China;

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  • 正文语种 eng
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  • 关键词

    Poly(urethane amide); Gene delivery; Disulfide; Imaging; Theranostics;

    机译：聚氨基甲酸酯基因传递;二硫化物;成像;治疗学;

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