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Peptide Gene Delivery Vectors for Specific Transfection of Glioma Cells
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-12-01 , DOI: 10.1021/acsbiomaterials.0c01336
Taoran Wang 1 , Zhao Meng 1 , Ziyao Kang 1 , Guihua Ding 1 , Baoquan Zhao 1 , Zhenbin Han 1 , Zhibing Zheng 1 , Chenhong Wang 1 , Qingbin Meng 1, 2
Affiliation  

Gene therapy offers an alternative approach to malignant glioma; however, glioma cells are difficult to transfect. Peptides, as nonviral vectors, can achieve efficient gene transfection in glioma cells due to their good biocompatibility and easy functionalization. In this article, we reported a series of peptide vectors, which were composed of amphiphilic α-helical segments, cationic cell-penetrating segments, and cysteine and glycine residues. The physicochemical properties of peptide vectors or peptide/pGL3 complexes, including conformation, DNA-loading capacity, size, zeta potential, and morphology, were characterized. Their gene delivery abilities were evaluated in U373, U87, and C6 glioma cell lines and a normal cell line 293 T. Compared with Lipo 2000 and other peptide vectors, the efficiency of P-03 (CLLHHLLHHLLHHGGRKKRRQRRR) to transfect glioma cells was higher. While in 293 T cells, the transfection efficiency of P-03 was much lower than that of Lipo 2000 and another positive control P-07. Furthermore, P-03 could facilitate the pGL3 plasmids crossing a blood–brain barrier model in vitro and achieved the expression of EGFP gene in the brain sites of zebrafish.

中文翻译:

胶质瘤细胞特异性转染的肽基因传递载体

基因治疗为恶性神经胶质瘤提供了另一种方法。但是,胶质瘤细胞难以转染。肽作为非病毒载体,由于其良好的生物相容性和易于功能化,可以在神经胶质瘤细胞中实现有效的基因转染。在本文中,我们报道了一系列肽载体,这些肽载体由两亲性α螺旋片段,阳离子细胞穿透片段以及半胱氨酸和甘氨酸残基组成。表征了肽载体或肽/ pGL3复合物的物理化学性质,包括构象,DNA负载能力,大小,ζ电位和形态。在U373,U87和C6胶质瘤细胞系和正常细胞293 T中评估了它们的基因传递能力。与Lipo 2000和其他肽载体相比,P-03(CLLHHLLHHLLHHGGRKKRRQRRR)转染神经胶质瘤细胞的效率较高。而在293 T细胞中,P-03的转染效率远低于Lipo 2000和另一个阳性对照P-07的转染效率。此外,P-03可以促进pGL3质粒在体外穿过血脑屏障模型,并在斑马鱼的大脑部位实现EGFP基因的表达。
更新日期:2020-12-14
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