Co-self-assembled Of Cationic Micelles To Deliver PEGFP-ZNF580 For Enhancing The Transfection And Migration Capability Of Endothelial Cells

Polyethylenimine(PEI)with high molecular weight has been demonstrated to have high gene transfection efficiency.However,its cytotoxicity limits further application in gene delivery in vivo.Herein,we developed a cationic gene carrier with high transfection efficiency and low cytotoxicity for the transfection of endothelial cells(ECs)in vitro.Firstly,a star copolymer of poly(3(S)-methyl-morpholine-2,5-dione-co-lactide)(P(MMD-co-LA))was synthesized using D-sorbitol as an initiator,and the cationic copolymer(P(MMD-co-LA)-g-PEI)was obtained after grafting low molecular weight PEI.Then,micelles were prepared by co-self-assembly of the cationic copolymer and a diblock copolymer methoxy-poly(ethylene glycol)-b-poly(3(S)-methyl-morpholine-2,5-dione-co-lactide)(mPEG-b-P(MMD-co-LA)).The core of micelles was consisted of a biodegradable block of P(MMD-co-LA),and the shell was formed by mPEG and PEI blocks.Finally,after condensation of pEGFP-ZNF580 by these micelles,the plasmids were protected from enzymatic hydrolysis effectively.The hydrodynamic size and zeta potential of blank and pEGFP-ZNF580-loaded micelles complexes were suitable for cellular uptake and gene transfection.When the mass ratio of mPEG-b-P(MMD-co-LA)to P(MMD-co-LA)-g-PEI was 3/1,MTT assay results demonstrated that the cytotoxicity of the complexes was very low at low concentration(30 ?g mL-1).The cell transfection results indicated that pEGFP-ZNF580 could be transported into ECs efficiently by these micelles/pEGFP-ZNF580 complexes.Wound healing assay showed that the transfected ECs recovered in 24 h.Cationic micelles designed in the present study should be a suitable non-viral gene carrier for the endothelialization of artificial blood vessels.