1. Galactosylated poly(ethylene glycol) methacrylate-st-3-guanidinopropyl methacrylamide copolymers as siRNA carriers for inhibiting Survivin expression in vitro and in vivo.
- Author
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Wu Y, Qin Z, Ji J, Yang R, Zhang X, Li Y, Yin L, Pu Y, and Li X
- Subjects
- Animals, Cell Survival drug effects, Cell Survival genetics, Drug Carriers chemical synthesis, Electrophoresis, Agar Gel, Female, Gene Transfer Techniques, Guanidines chemical synthesis, HeLa Cells, Hep G2 Cells, Humans, Mice, Inbred BALB C, Molecular Structure, Neoplasms, Experimental genetics, Neoplasms, Experimental pathology, Neoplasms, Experimental therapy, Particle Size, Polymethacrylic Acids chemical synthesis, Surface Properties, Survivin, Transfection, Xenograft Model Antitumor Assays, Drug Carriers chemistry, Gene Expression drug effects, Guanidines chemistry, Inhibitor of Apoptosis Proteins genetics, Polymethacrylic Acids chemistry, RNA, Small Interfering administration & dosage, RNA, Small Interfering genetics
- Abstract
In this report, galactosylated poly(ethylene glycol) methacrylate-st-3-guanidinopropyl methacrylamide 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 +14.9 mV 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.
- Published
- 2014
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