Gd(III) ion-chelated supramolecular assemblies composed of PGMA-based polycations for effective biomedical applications

Gd(III) ion-chelated supramolecular assemblies composed of PGMA-based polycations for effective biomedical applications
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由基于 PGMA 的聚阳离子组成的 Gd(III) 离子螯合超分子组件,用于有效的生物医学应用

DOI:
10.1038/am.2015.67
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发表时间:
2015-07
期刊:
影响因子:
9.7
通讯作者:
Xu Fu-Jian
Xu Fu-Jian
中科院分区:
材料科学2区
文献类型:
--
作者:
Zhao Yu;Duan Shun;Yu Bingran;Liu Fu-Sheng;Cheng Gang;Xu Fu-Jian

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乙醇胺(EA)或乙二胺(艾德)功能化的聚甲基丙烯酸缩水甘油酯(PGMA),即PGEA或PG艾德,由于其低细胞毒性和高转染效率,最近被用作有效的基因载体。本研究通过将多个金刚烷头星星型PGEA(Ad-PGEA)单元与多功能的PGED-CD-Gd骨架组装在一起,构建了一系列具有磁共振成像(MRI)功能的PGMA基超分子聚阳离子(PGED-Gd@PGEAs)。系统地研究了PGED-Gd@PGEA载体的性质,包括质粒DNA凝聚能力、细胞毒性、基因转染效率、细胞摄取和MRI功能。这种超分子基因载体具有比“金标准”聚乙烯亚胺(PEI,25 kDa)更低的毒性。此外,PGED-Gd@PGEAs表现出比PEI或组成单元(PGED-CD-Gd和Ad-PGEA)显著更高的转染效率。Gd ~(3+)离子的螯合作用使PGED-Gd@PGEA载体具有良好的磁共振成像能力,且无明显不良反应。本研究设计的具有Gd ~(3+)螯合作用的PGMA基超分子聚阳离子为开发低毒、高效的多功能基因传递系统提供了有用的信息。一种复杂的聚合物复合物可以高效低毒地将基因携带到细胞靶点。基因治疗有可能彻底改变癌症等疾病的治疗,但需要非病毒基因递送系统来确保患者安全。北京化工大学的徐福健及其同事已经采取措施,通过将阳离子聚合物和钆(Gd)离子组装成球形超分子主客体复合物来实现这一目标。这些基于生物相容性聚(甲基丙烯酸缩水甘油酯)和环糊精分子的化合物可以进行尺寸调节,以确保纳米颗粒具有最佳细胞摄取的正确尺寸。Gd离子的添加将多功能递送装置转变为用于核酸转移的体内监测的磁共振成像探针。
Ethanolamine (EA) or ethylenediamine (ED)-functionalized poly(glycidyl methacrylate) (PGMA), namely PGEA or PGED, has recently been used as effective gene carriers because of their low cytotoxicity and high transfection efficiency. In this study, a series of PGMA-based supramolecular polycations (PGED-Gd@PGEAs) with magnetic resonance imaging (MRI) functions were readily constructed by assembling multiple adamantine-headed star PGEA (Ad-PGEA) units with a versatile PGED-CD-Gd backbone, which possessed numerous flanking β-cyclodextrin species and Gd3+ ions. The properties of different PGED-Gd@PGEA vectors were systematically characterized, including the plasmid DNA condensation ability, cytotoxicity, gene transfection efficiency, cellular uptake and MRI function. Such supramolecular gene vectors had lower toxicity than ‘gold standard’ polyethylenimine (PEI, 25 kDa). Furthermore, PGED-Gd@PGEAs exhibited significantly higher transfection efficiencies than PEI or the constituent units (PGED-CD-Gd and Ad-PGEA). The chelation of Gd3+ ions imparted the PGED-Gd@PGEA vectors with a good MRI ability without obvious adverse effects. The present design of PGMA-based supramolecular polycations with Gd3+ chelation would provide useful information for the development of low-toxicity and high-efficiency multifunctional gene delivery systems. An intricate polymer complex can carry genes to their cellular targets with high efficiency and low toxicity. Gene therapy has the potential to revolutionize the treatment of diseases such as cancer, but non-viral gene delivery systems are needed to ensure patient safety. Fu-Jian Xu from the Beijing University of Chemical Technology and co-workers have taken steps to reach this goal by assembling cationic polymers and gadolinium (Gd) ions into spherical, supramolecular host-guest complexes. These compounds, based on biocompatible poly(glycidyl methacrylate) and cyclodextrin molecules, can be size adjusted to ensure the nanoparticles have the correct dimensions for optimal cellular uptake. The addition of Gd ions turns the multifunctional delivery device into a magnetic resonance imaging probe for in vivo monitoring of nucleic acid transfer.
由 2-羟丙基-β-环糊精、乙醇胺功能化聚(甲基丙烯酸缩水甘油酯)和聚((2-二甲基氨基)甲基丙烯酸乙酯)组成的高效基因载体,通过 ATRP 和点击化学相结合
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