Peptide Gene Delivery Vectors for Specific Transfection of Glioma Cells.

Abstract

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.