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Galactosylated poly(ethylene glycol) methacrylate-st-3-guanidinopropyl methacrylamide copolymers as siRNA carriers for inhibiting Survivin expression in vitro and in vivo

文献类型： 外文期刊

作者： Wu, Yang 1 ; Qin, Zhu 1 ; Ji, Jinkai 1 ; Yang, Ran 1 ; Zhang, Xiaoqiang 3 ; Li, Yuanhui 3 ; Yin, Lihong 3 ; Pu, Yuepu 3 ; Li 1 ;

作者机构： 1.Southeast Univ, Sch Chem & Chem Engn, Biomat & Drug Delivery Labs, Nanjing 211189, Jiangsu, Peoples R China

2.Jiangsu Acad Agr Sci, Inst Agr Facil & Equipment, Nanjing, Jiangsu, Peoples R China

3.Southeast Univ, Sch Publ Hlth, Key Lab Med Engn & Environm, Nanjing, Jiangsu, Peoples R China

关键词： Gene delivery;siRNA;Survivin;targeting

期刊名称：JOURNAL OF DRUG TARGETING （ 影响因子：5.121； 五年影响因子：5.024 ）

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收录情况： SCI

摘要： In this report, galactosylated poly(ethylene glycol) methacrylate-st-3-guanidinopropyl metha-crylamide copolymers (galactosylated PEGMA-st-GPMA, GGP) are developed as siRNA carriers to inhibit Survivin mRNA expression. GGPs are combined with Survivin siRNAs to form siRNA/GGP polyplexes. The polyplexes particles were examined by a dynamic light scattering. It showed that GGP copolymers could condense siRNA to form particles with diameter from 128 to 423 nm and zeta potential value in the range from +2.4 to +14.9mV at various charge ratios (N/P). The MTT assay data of siRNA/GGP polyplexes on human hepatocellular liver carcinoma cells (HepG2) and human cervix epithelial carcinoma cells (HeLa) indicated that GGP copolymer had better cell viabilities than polyethyleimine (PEI). The transfection of siRNA/GGP polyplexes was detected by real-time quantitative PCR (RT-qPCR) in HepG2 cell line. We found that the siRNA/GGP polyplexes could effectively silence Survivin mRNA expression in the serum-free media (p<0.01). In the presence of 10% serum medium, the Survivin mRNA expressed has significant difference between siRNA/GGP polyplexes and blank (p<0.05). The galactose competition assay showed that galactosylated PEGMA-st-GPMA (GGP) may provide the targeting to HepG2 cells mediating by asialoglycoproteins receptors (ASGP-R). Furthermore, Survivin siRNA/GGP polyplexes could significantly (p<0.01) inhibit both HepG2 tumor growth and Survivin protein expression in vivo studies in a xenograft mouse model.

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