PURPOSE: 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. METHODS: 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. RESULTS: The weight ratio of polymer:RNA was 15:1 and a nanocomplex system consisting of <200 nm 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. CONCLUSION: 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.
PURPOSE: 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. METHODS: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. RESULTS: The weight ratio of polymer:RNA was 15:1 and a nanocomplex system consisting of <200 nm 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. CONCLUSION: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.
Authors: Brian Dalby; Sharon Cates; Adam Harris; Elise C Ohki; Mary L Tilkins; Paul J Price; Valentina C Ciccarone Journal: Methods Date: 2004-06 Impact factor: 3.608
Authors: John DeVincenzo; Robert Lambkin-Williams; Tom Wilkinson; Jeffrey Cehelsky; Sara Nochur; Edward Walsh; Rachel Meyers; Jared Gollob; Akshay Vaishnaw Journal: Proc Natl Acad Sci U S A Date: 2010-04-26 Impact factor: 11.205
Authors: Hideo Niwa; Abbey L Wentzel; Mengfeng Li; William E Gooding; Vivian Wai Yan Lui; Jennifer Rubin Grandis Journal: Clin Cancer Res Date: 2003-10-15 Impact factor: 12.531