Apoptosis of A549 cells by small interfering RNA targeting survivin delivery using poly-β-amino ester/guanidinylated O-carboxymethyl chitosan nanoparticles

被引:36
作者
Tang, Yue [1 ]
Liu, Yun [1 ]
Xie, Yuwen [1 ]
Chen, Jing [1 ]
Dou, Yushun [1 ]
机构
[1] China Pharmaceut Univ, Dept Pharm, Nanjing 211198, Peoples R China
关键词
Poly-beta-amino ester; Guanidinylated O-carboxymethyl chitosan; Nanoparticles; Gene delivery; GENE-THERAPY; IN-VITRO; SIRNA; CHALLENGES; STRATEGIES; COMPLEXES; CARRIERS;
D O I
10.1016/j.ajps.2018.09.009
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Gene-based therapeutics has emerged as a promising approach for human cancer therapy. Among a variety of non-viral vectors, polymer vectors are particularly attractive due to their safety and multivalent groups on their surface. This study focuses on guanidiny-lated O-carboxymethyl chitosan (GOCMCS) along with poly-beta-amino ester(PBAE) for siRNA delivery. Binding efficiency of PBAE/siRNA/GOCMCS nanoparticles were characterized by gel electrophoresis. The siRNA-loaded nanoparticles were found to be stable in the presence of RNase A, serum and BALF respectively. Fine particle fraction (FPF) which was determined by a two-stage impinger (TSI) was 57.8% +/- 12.6%. The particle size and zeta potential of the nanoparticles were 153.8 +/- 12.54 nm and + 12.2 +/- 4.94 mV. In vitro cell transfection studies were carried out with A549 cells. The cellular uptake was significantly increased. When the cells were incubated with siSurvivin-loaded nanoparticles, it could induce 26.83% +/- 0.59% apoptosis of A549 cells and the gene silencing level of survivin expression in A549 cells were 30.93% +/- 2.27%. The results suggested that PBAE/GOCMCS nanoparticle was a very promising gene delivery carrier. (C) 2019 Published by Elsevier B.V. on behalf of Shenyang Pharmaceutical University.
引用
收藏
页码:121 / 128
页数:8
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