Song Hai-Qing, Li Rui-Quan, Duan Shun, Yu Bingran, Zhao Hong, Chen Da-Fu, Xu Fu-Jian
State Key Laboratory of Chemical Resource Engineering, College of Materials Science & Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
Nanoscale. 2015 Mar 19;7(13):5803-14. doi: 10.1039/c4nr07515c.
Polypeptide-based degradable polyplexes attracted considerable attention in drug delivery systems. Polysaccharides including cyclodextrin (CD), dextran, and chitosan (CS) were readily grafted with cationic poly(aspartic acid)s (PAsps). To further enhance the transfection performances of PAsp-based polyplexes, herein, different types of ligand (folic acid, FA)-functionalized degradable polyplexes were proposed based on the PAsp-grafted chitosan-cyclodextrin conjugate (CCPE), where multiple β-CDs were tied on a CS chain. The FA-functionalized CCPE (i.e., CCPE-FA) was obtained via a host-guest interaction between the CD units of CCPE and the adamantane (Ad) species of Ad-modified FA (Ad-FA). The resulting CCPE/pDNA, CCPE-FA/pDNA, and ternary CCPE-FA/CCPE/pDNA (prepared by layer-by-layer assembly) polyplexes were investigated in detail using different cell lines. The CCPE-based polyplexes displayed much higher transfection efficiencies than the CS-based polyplexes reported earlier by us. The ternary polyplexes of CCPE-FA/CCPE/pDNA produced excellent gene transfection abilities in the folate receptor (FR)-positive tumor cells. This work would provide a promising means to produce highly efficient polyplexes for future gene therapy applications.
基于多肽的可降解多聚体在药物递送系统中引起了广泛关注。包括环糊精（CD）、葡聚糖和壳聚糖（CS）在内的多糖很容易与阳离子聚天冬氨酸（PAsp）接枝。为了进一步提高基于PAsp的多聚体的转染性能，在此，基于PAsp接枝的壳聚糖-环糊精共轭物（CCPE）提出了不同类型的配体（叶酸，FA）功能化的可降解多聚体，其中多个β-CD连接在CS链上。通过CCPE的CD单元与金刚烷（Ad）修饰的FA（Ad-FA）的金刚烷物种之间的主客体相互作用获得FA功能化的CCPE（即CCPE-FA）。使用不同的细胞系详细研究了所得的CCPE/pDNA、CCPE-FA/pDNA和三元CCPE-FA/CCPE/pDNA（通过逐层组装制备）多聚体。基于CCPE的多聚体表现出比我们之前报道的基于CS的多聚体更高的转染效率。CCPE-FA/CCPE/pDNA的三元多聚体在叶酸受体（FR）阳性肿瘤细胞中产生了优异的基因转染能力。这项工作将为未来基因治疗应用生产高效多聚体提供一种有前景的方法。
