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多臂聚(L-谷氨酸)-接枝-聚丙烯亚胺作为有效且抗血清的基因传递载体。

Multi-armed poly(L-glutamic acid)-graft-polypropyleneinime as effective and serum resistant gene delivery vectors.

机构信息

Shenzhen Mental Health Center, 1080 Cuizhu Road, Shenzhen 518020, PR China; Shenzhen Key Lab for Psychological Healthcare, 1080 Cuizhu Road, Shenzhen 518020, PR China.

School of Biosciences and Biopharmaceutics, Guang Dong Pharmaceutical University, 280 Waihuan East Road, Guangzhou 510006, PR China.

出版信息

Int J Pharm. 2014 Apr 25;465(1-2):444-54. doi: 10.1016/j.ijpharm.2014.02.041. Epub 2014 Feb 25.

DOI:10.1016/j.ijpharm.2014.02.041
PMID:24576809
Abstract

A new series of multi-armed MP-g-PPI dendrimers were synthesized by polymerization of BLG-NCA using G2.0PPI as macromolecular initiator and subsequent aminolysis with G1.0PPI or G2.0PPI. The chemical structure and composition of the MP-g-PPI dendrimers were characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy ((1)H NMR). The MP-g-PPI showed a great ability to combine with pDNA to form complexes, which protect the pDNA from nuclease degradation. Dynamic light scattering (DLS) measurement illustrated that the sizes of complexes were in range of 111-219 nm. The transmission electron microscope (TEM) and atomic force microscope (AFM) observation showed that the morphology of these complexes was spherical. The MTT assay demonstrated that cytotoxicity of the MP-g-PPI was lower than that of PEI 25K. The in vitro transfection test indicated that MP-g-PPI gene vectors displayed relative high transfection efficiency than that of PEI 25K and Lipofectamine 2000 in serum-containing medium. Furthermore, MP-g-PPI at the weight ratio of 7.5 displayed better serum-resistant capability than that of PEI 25K and Lipofectamine 2000. The above facts revealed that multi-armed MP-g-PPI dendrimers may be promising gene vectors with low cytotoxicity, high transfection efficiency and serum-resistant ability.

摘要

一系列新型多臂 MP-g-PPI 树枝状聚合物是通过 BLG-NCA 的聚合反应,以 G2.0PPI 作为大分子引发剂,然后用 G1.0PPI 或 G2.0PPI 进行氨解反应合成的。MP-g-PPI 的化学结构和组成通过傅里叶变换红外光谱(FT-IR)和核磁共振谱((1)H NMR)进行了表征。MP-g-PPI 具有与 pDNA 结合形成复合物的巨大能力,能够保护 pDNA 免受核酸酶的降解。动态光散射(DLS)测量表明,复合物的大小在 111-219nm 范围内。透射电子显微镜(TEM)和原子力显微镜(AFM)观察表明,这些复合物的形态为球形。MTT 测定表明,MP-g-PPI 的细胞毒性低于 25kDa 的 PEI。体外转染试验表明,在含血清的培养基中,MP-g-PPI 基因载体的转染效率明显高于 25kDa 的 PEI 和 Lipofectamine 2000。此外,MP-g-PPI 在重量比为 7.5 时,比 25kDa 的 PEI 和 Lipofectamine 2000 具有更好的耐血清能力。上述事实表明,多臂 MP-g-PPI 树枝状聚合物可能是一种具有低细胞毒性、高转染效率和耐血清能力的有前途的基因载体。

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