Binary gene vectors based on hyperbranched poly(l-lactide-co-polyglycerol) and polyethylenimine for prolonged transgene expression via co-assembly with DNA into fiber core-shell triplexes.
Binary gene vectors based on hyperbranched poly(l-lactide-co-polyglycerol) and polyethylenimine for prolonged transgene expression via co-assembly with DNA into fiber core-shell triplexes.
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DOI：
10.1039/c3tb21150a
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发表时间：
2013-11
期刊：
影响因子：
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通讯作者：
Lei Zhang;Chaohua Hu;Yiwen Fan;Yunkun Wu
中科院分区：
文献类型：
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作者：
Lei Zhang;Chaohua Hu;Yiwen Fan;Yunkun Wu
合成了基于亲水性超支化聚甘油（PG 6）和酯链聚乳酸（PLA）的超支化PG 6-PLA聚合物，并促进开发了一种新型生物相容性控释基因载体。通过NMR、FT-IR和SEC-MALLS分析证实了PG 6-PLA的超支化结构。讨论了PG 6-PLA与25 kDa高分子量聚乙烯亚胺（PEI）的共组装。透射电镜、荧光示踪和尺寸/zeta电位分析结果表明，PG 6-PLA/PEI 25 k/DNA可以形成新型的纤维核壳结构。体外细胞实验表明，PG 6-PLA显著增强了PEI 25 k在人胚肾细胞系293 T和人宫颈癌细胞系HeLa中的细胞内滞留和介导荧光素酶和EGFP表达的能力，并伴随着细胞生物相容性的改善和转基因表达时间的延长。重要的是，二元载体PG 6-PLA/PEI 25 k对一些肿瘤细胞系（包括HeLa和HepG 2人肝癌细胞系）表现出特异性亲和力。这些结果表明，基于纤维核壳结构的PG 6-PLA/PEI 25 k/DNA基因传递系统可以作为一种基因传递系统，介导更有效的转基因表达。
Hyper-branched PG6-PLA polymers based on hydrophilic hyperbranched polyglycerol (PG6) and the ester chain poly(l-lactide) (PLA) were synthesized and facilitated to develop a novel biocompatible release-controlled gene vector. The hyper-branched structure of PG6-PLA was verified by NMR, FT-IR and SEC-MALLS analysis. The co-assembly of PG6-PLA with high molecular weight polyethylenimine (PEI) of 25 kDa was discussed. The results of TEM, fluorescence tracking and size/zeta-potential analysis revealed that the PG6-PLA/PEI25k/DNA could co-assemble to generate a novel fiber core-shell conformation. In vitro cell experiment demonstrated that PG6-PLA significantly enhanced the ability of PEI25k to remain within cells and mediate luciferase and EGFP expression in the human embryonic kidney cell line 293T and human cervical carcinoma cell line HeLa, which was accompanied by improved cell biocompatibility and an extended period of transgene expression. Importantly, the binary vector PG6-PLA/PEI25k exhibited specific affinity to some tumour cell lines including HeLa and the HepG2 human hepatoma cell line. These results suggested that the novel gene delivery system based on fiber core-shell PG6-PLA/PEI25k/DNA can serve as a gene delivery system to mediate more efficient transgene expression.