title: Chitosan-based hybrid nanocomplex for siRNA delivery and its application for cancer therapy.
abstract: OBJECTIVE
  Chitosan, a natural and biocompatible cationic polymer, is an attractive carrier for small interfering RNA (siRNA) delivery. The purpose of this study was to develop a chitosan-based hybrid nanocomplex that exhibits enhanced physical stability in the bloodstream compared with conventional chitosan complexes. Hybrid nanocomplexes composed of chitosan, protamine, lecithin, and thiamine pyrophosphate were prepared for systemic delivery of survivin (SVN) siRNA.
  
  
  METHODS
  Physicochemical properties of the nanoparticles including mean diameters and zeta potentials were characterized, and target gene silencing and cellular uptake efficiencies of the siRNA nanocomplexes in prostate cancer cells (PC-3 cells) were measured. In vivo tumor targetability and anti-tumor efficacy by systemic administration were assessed in a PC-3 tumor xenograft mouse model by near-infrared fluorescence (NIRF) imaging and tumor growth monitoring, respectively.
  
  
  RESULTS
  Mean diameters of the SVN siRNA-loaded hybrid nanocomplex (GP-L-CT) were less than 200 nm with a positive zeta potential value in water and were maintained without aggregation in culture media and 50% fetal bovine serum. SVN expression in PC-3 cells was reduced to 21.9% after treating with GP-L-CT. The tumor targetability and growth inhibitory efficacies of GP-L-CT supported the use of this novel hybrid nanocomplex as a cancer therapeutic and as a theranostic system for systemic administration.
  
  
  CONCLUSIONS
  A chitosan-based hybrid nanocomplex was successfully developed for the systemic delivery of SVN siRNA, which could serve as an alternative to cationic polymeric nanoparticles that are unstable in serum.
authors.affiliation: Chong Kun Dang Research Institute, Chong Kun Dang Pharm., Yongin, 446-916, Republic of Korea.
authors.forename: Min-Hyo
authors.initials: MH
authors.lastname: Ki
authors.forename: Ji-Eon
authors.initials: JE
authors.lastname: Kim
authors.forename: Young-Nam
authors.initials: YN
authors.lastname: Lee
authors.forename: Sang Myoung
authors.initials: SM
authors.lastname: Noh
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: An
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000627:therapeutic use*; D014162:Transfection / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D048271:Chitosan