Synthesis and evaluation of a dendritic poly(L-glutamic acid)-graft-polyethylenimine copolymer as an efficient gene delivery vector
10.16438/j.0513-4870.2018-1143
- VernacularTitle:聚酰胺-胺-聚谷氨酸-聚乙烯亚胺共聚物的制备及作为基因载体的性能研究
- Author:
Ying CHEN
1
;
Jin-fang HU
2
;
Chang-lin ZHANG
3
;
Duan-wen CAO
2
;
Xiao-hua WEI
1
Author Information
1. Clinical Trial Research Center, Department of Pharmacy, the First Affiliated Hospital; School of Pharmacy, Nanchang University, Nanchang 330006, China
2. Clinical Trial Research Center, Department of Pharmacy, the First Affiliated Hospital
3. Department of Clinical Laboratory, the First Affiliated Hospital
- Publication Type:Research Article
- Keywords:
poly (amidoamine);
poly(L-glutamic acid);
polyethyleneimine;
copolymer;
gene vector
- From:
Acta Pharmaceutica Sinica
2019;54(5):919-926
- CountryChina
- Language:Chinese
-
Abstract:
The study was designed to synthesize a novel dendritic copolymer composed of polyamidoamine dendrimer G0 as the inner core and poly(L-glutamic acid) grafted low molecular weight polyethylenimine (PGLP) as surrounding arms for gene delivery vector. The molecular structure of PGLP was confirmed by 1H NMR (proton nuclear magnetic resonance spectroscopy). The DNA combination capability of PGLP was examined by gel retardation electrophoresis. The particle sizes and zeta potentials of PGLP/pDNA complexes were determined by dynamic light scattering (DLS). The cytotoxicity of PGLP was evaluated by Cell Counting Kit-8 (CCK-8) and hemolysis assays, which was approved by Research Ethics Committee of the First Affiliated Hospital of Nanchang University. The in vitro transfection efficiency of PGLP was measured by a flow cytometry. The results of physicochemical properties suggested that PGLP could self-assemble with DNA to form complexes with average particle sizes of about 105-200 nm and zeta potentials of about +10 - +28 mV, which could protect DNA from serum degradation. The results of biological properties suggested that PGLP showed more higher transfection efficiencies but lower cytotoxicity than PEI 25K or Lipofectamine 2000 in various cell lines (HEK 293T, HeLa, BEL 7402, RASMC). Importantly, it was found that PGLP/pDNA complexes at w/w = 8 showed more strong serum-resistant capacity than PEI 25K/pDNA complexes. Therefore, PGLP is a promising candidate vector for gene delivery.
