Self-Assembly of Polyethylenimine-Modified Biodegradable Complex Micelles as Gene Transfer Vector for Proliferation of Endothelial Cells

Abstract

Polyethylenimine (PEI) can perfectly condense with DNA and sufficiently transfer genes, but its high toxicity limits its application. Here, complex micelles are prepared as low-toxicity gene vectors by self-assembly of two block copolymers in aqueous solution. The complex micelles consist of a biodegradable poly(lactide-co-glycolide) (PLGA) core and a mixed poly(ethylene glycol) (PEG)/PEI shell. The ZNF580 gene plasmid (pEGFP-ZNF580), which has the ability of enhancing the proliferation of vascular endothelial cells, is encapsulated into the complex micelles. Using dynamic light scattering, the degradation behavior of the micelles is investigated in vitro. The hydrodynamic size and zeta potential of blank and DNA-loaded micelles are feasible to cellular uptake and gene transfection. 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay shows that the cytotoxicity of the complex micelles is very low when the PEG/PEI ratio is 3/1. The DNA-loaded micelles are found to be able to enhance the proliferation of endothelial cells.