科研之友
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摘要
Background Small interfering RNA (siRNA) has been recognized as a new therapeutic drug to treat various diseases by inhibition of oncogene or viral gene expression. Because hyaluronic acid (HA) has been described as a biocompatible biomaterial, we tested the nanoparticles formed by electrostatic complexation of negatively-charged HA and cationic Poly L-arginine (PLR) for siRNA delivery systems. Methods Different electrostatic complexes of HA and PLR (HPs) were formulated: HP101 with 50% (w/w) HA and HP110 with 9% (w/w) HA. Results Gel retardation assays showed that HP101 and HP110 could form complexes with siRNAs. The diameters of these complexes were less than 200 nm. Cellular delivery efficiency of siRNAs by HPs depended on cell surface CD44 density. The HP-mediated delivery of siRNAs was highest in WM266.4 cells followed by B16F10 cells and COS-7 cells, in parallel with CD44 surface densities of these cell lines. TC(50) values (i.e. the HP concentrations at which 50% of cells were viable after treatment) were used as indicators of cytotoxicity. HP101 showed TC50 values that were 2-fold and 23-fold higher than those of HP110 and PLR, respectively. After delivery into cells, siRNA exerted target-specific RNA interference effects on mRNA and protein levels. Three days after treatment of red fluorescent protein (RFP)-expressing B16F10 cells with RFP-specific siRNA complexed to HP101, cellular fluorescence signals were reduced. intratumoral administration of RFP-specific siRNA via HP101 delivery significantly reduced the expression of RFP in tumor tissues. Conclusions HP101 may function as a biocompatible polymeric carrier of siRNAs and have possible application to localized siRNA delivery in vivo.
- 出版日期2009-9
