title: Poly-L-arginine and dextran sulfate-based nanocomplex for epidermal growth factor receptor (EGFR) siRNA delivery: its application for head and neck cancer treatment.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Republic of Korea.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
authors.forename: Saeho
authors.initials: S
authors.lastname: Chong
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
authors.forename: Chang-Koo
authors.initials: CK
authors.lastname: Shim
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D016264:Dextran Sulfate / Q000737:chemistry* / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020868:Gene Silencing / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000628:therapy; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D010455:Peptides; D034741:RNA, Small Interfering; C015462:polyarginine; D016264:Dextran Sulfate; D066246:ErbB Receptors