Abstract
A poly-L-arginine (PLR) and dextran sulfate (DEX)-based nano-sized polyelectrolyte complex (nanocomplex) was developed for epidermal growth factor receptor (EGFR) siRNA delivery for the treatment of head and neck cancer. PLR and DEX-based nanocomplex including EGFR siRNA was prepared and characterized. In vitro cellular uptake efficiency and EGFR gene silencing effect of nanocomplex including EGFR siRNA were evaluated in Hep-2 and FaDu cells. Its in vivo anti-tumor efficacy was also assessed in FaDu tumor xenografted mouse model. The weight ratio of polymer:RNA was 15:1 and a nanocomplex system consisting of <200nm in mean diameter and a positive surface charge was prepared. According to the results of confocal laser scanning microscopy (CLSM) and flow cytometry analyses, the PLR-DEX complex exhibited the best cellular uptake efficiency of EGFR siRNA in Hep-2 and FaDu cells, which led to the highest EGFR gene silencing efficiency in both cell lines. PLR-DEX/EGFR siRNA complex exhibited efficient tumor growth inhibition and EGFR silencing effect in a tumor xenografted mouse model. PLR and DEX-based nanocomplex containing EGFR siRNA was successfully developed. The new formulation was effective in EGFR gene silencing and tumor growth inhibition in head and neck cancer cells.
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