A Novel Nonviral Gene Delivery Vector
|Keywords||non-viral gene vector polyaspartamide polyethylenimine folate fibroblast growth factor gene vector|
Objective:To develop a novel gene delivery vector withα,β-poly-(N-2-hydroxy-propyl)-D,L-aspartamide (PHPA) as backbone modified with low molecular weight polyethylenimine (PEI600). We described the use of folate or fibroblast growth factor receptor grafted PHPA-PEI as an effective polyplex-forming plasmid delivery agent with low toxicity.Methods:PHPA was synthesized from polysuccinimide and low molecular weight polyethylenimine (PEI600) was grafted to form copolymer PHPA-PEI. Then the target ligand:folate or fibroblast growth factor receptor (peptide, CY11) was conjugated to the amino group on polyethylenimine of the backbone. Chemical and biological characterization were identified the copolymers, such as Nuclear Magnetic Resonance Spectroscopy, particle size and zeta potential test, the gel retardation assay, MTT cytotoxicity assay, transfection efficiency experiments et al.Results:PHPA-PEI had been synthesized and characterized by the 1H-NMR spectrum. Folate and peptide (CY11) were conjugated to PHPA-PEI respectively, confirmed by 1H-NMR and UV spectrum. Folate and peptide CY11 both showed low cytotoxicity and high transfection efficiency. To PHPA-PEI-FOL, its transfection efficiency was 2.5-fold higher than that of PEI25kD at N/P ratio of 20 at the absence of serum in HeLa cells.Conclusion:The novel vectors PHPA-PEI-FOL and PHPA-PEI-CY11 with low cytotoxicity and high transfection efficiency, which may be used as a potential targeting carrier for HeLa cells in gene delivery.