title: PEG-PCL-DEX polymersome-protamine vector as an efficient gene delivery system via PEG-guided self-assembly.
abstract: OBJECTIVE
  The nonviral carrier system based on the triblock copolymer PEG-PCL-DEX (PPD) and protamine was developed for nucleic acid delivery.
  
  
  METHODS
  Self-assembly occurred in the PEG continuous phase to form 'dextran-interior' polymersomes. siRNA can be condensed by protamine and encapsulated into PPD polymersomes in order to form the PPD-protamine siRNA nanoparticles by thermodynamically preferential partition between the PEG continuous phase and the dextran cavity.
  
  
  RESULTS
  This system can package siRNA into PPD polymersomes to form 145.2 ± 8.02-nm (± standard deviation) nanoparticles, and the ζ-potential can be reduced to approximately 0 mV. PPD-protamine siRNA nanoparticles achieved cellular uptake of siRNA in SMMC-7721 cells with negligible cytotoxicity, and the GL3 gene expression can be reduced to 61.73 ± 6.25%. A biodistribution study of nanoparticles suggested that the PPD-protamine siRNA nanoparticles mainly accumulated in liver.
  
  
  CONCLUSIONS
  All of these results suggest that PPD-protamine carriers may offer a promising gene delivery strategy for the treatment of liver-related disease.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, No. 800, Dongchuan Road, Shanghai 200240, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Ge
authors.forename: Qixin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Cai
authors.forename: Shiyue
authors.initials: S
authors.lastname: Duan
authors.forename: Shun
authors.initials: S
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Lv
authors.forename: Tuo
authors.initials: T
authors.lastname: Jin
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Chen
authors.forename: Weien
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry*; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011479:Protamines / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D014162:Transfection / Q000379:methods*
chemical_list: D003911:Dextrans; D011479:Protamines; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols
keywords: cytotoxicity; gene therapy; in vivo test; polyethylene oxide; polymersomes; protamine