title: Galactosylated poly(ethylene glycol) methacrylate-st-3-guanidinopropyl methacrylamide copolymers as siRNA carriers for inhibiting Survivin expression in vitro and in vivo.
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.
authors.affiliation: Biomaterials and Drug Delivery Laboratories, School of Chemistry and Chemical Engineering, Southeast University , Nanjing , P. R. China .
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.forename: Zhu
authors.initials: Z
authors.lastname: Qin
authors.forename: Jinkai
authors.initials: J
authors.lastname: Ji
authors.forename: Ran
authors.initials: R
authors.lastname: Yang
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Li
authors.forename: Lihong
authors.initials: L
authors.lastname: Yin
authors.forename: Yuepu
authors.initials: Y
authors.lastname: Pu
authors.forename: Xingsong
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D018014:Gene Transfer Techniques; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics*; D013499:Surface Properties; D000077022:Survivin; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C107489:BIRC5 protein, human; D004337:Drug Carriers; D006146:Guanidines; D051034:Inhibitor of Apoptosis Proteins; D011109:Polymethacrylic Acids; D034741:RNA, Small Interfering; D000077022:Survivin