Fabrication of a novel core-shell gene delivery system based on a brush-like polycation of alpha, beta-poly (L-aspartate-graft-PEI).
OBJECTIVE
A novel core-shell gene delivery system was fabricated in order to improve its gene transfection efficiency, particularly in the presence of serum.


METHODS
alpha, beta-poly (L-aspartate-graft-PEI) (PAE) was simply synthesized by ring-opening reaction of poly (L-succinimide) with low molecular weight (LMW) linear polyethylenimine (PEI, Mn = 423). PAE/DNA nanoparticles were characterized. Condensation and protection ability of plasmid by PAE were confirmed by agarose gel electrophoresis assay. Cytotoxicity of the polymer and polymer/DNA nanoparticles were measured by MTS assay. Gene transfection efficiencies were evaluated both in vitro and in vivo.


RESULTS
Core-shell nanoparticles assembled between DNA and PAE showed positive zeta potential, narrow size distribution, and spherical compact shapes with size below 250 nm when N/P ratio is above 10. Cytotoxicity of PAE was rather lower than that of PEI 25K, while the most efficient gene transfection and serum resistant ability of PAE/DNA complexes were higher than that of PEI 25K. Bafilomycin A1 treatment suggested "proton sponge" mechanism of PAE-mediated gene transfection. PAE/pEGFP-N2 nanoparticles also showed good gene expression in vivo and were dominantly distributed in kidney, liver, spleen and lung after intravenous administration.


CONCLUSIONS
The results demonstrated the potential use of PAE as an effective gene carrier.
Yu
Jia-Hui
JH
Department of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
Quan
Ji-Shan
JS
Kwon
Jung-Taek
JT
Xu
Cheng-Xiong
CX
Sun
Bo
B
Jiang
Hu-Lin
HL
Nah
Jae-Woon
JW
Kim
Eun-Mi
EM
Jeong
Hwan-Jeong
HJ
Cho
Myung-Haing
MH
Cho
Chong-Su
CS
D001224:Aspartic Acid / Q000737:chemistry*; D002412:Cations; D002460:Cell Line; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D006801:Humans; D008970:Molecular Weight; D053758:Nanoparticles; D011094:Polyethyleneimine / Q000737:chemistry*
D002412:Cations; D001224:Aspartic Acid; D011094:Polyethyleneimine