title: Recombinant high density lipoprotein nanoparticles for target-specific delivery of siRNA.
abstract: OBJECTIVE
  Regulation of gene expression using small interfering RNA (siRNA) is a promising strategy for treatments of numerous diseases. However, the progress towards broad application of siRNA requires the development of safe and effective vectors that target to specific cells. In this study, we developed a novel recombinant high density lipoprotein (rHDL) vector with high siRNA encapsulation efficiency.
  
  
  METHODS
  They were prepared by condensing siRNA with various commercial cationic polymers and coating the polyplex with a layer of lipids and apolipoprotein AI (apo AI). The rHDL nanoparticles were used to transfect SMMC-7721 hepatoma cells with stable luciferase expression. The uptake and intracellular trafficing of siRNA were also investigated.
  
  
  RESULTS
  Characterization studies revealed these rHDL nanoparticles had similar physical properties as natural HDLs. The various rHDL formulations had high silencing efficiency (more than 70% knockdown) in hepatocytes with minimum cytotoxicity. Moreover, the uptake of rHDL by SMMC-7721 was confirmed to be mediated through the natural HDL uptake pathway.
  
  
  CONCLUSIONS
  The work described here demonstrated the optimized rHDL nanoparticles may offer a promising tool for siRNA delivery to the liver.
authors.affiliation: School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, 200240, People's Republic of China.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Rui
authors.forename: Hailing
authors.initials: H
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wei
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D045744:Cell Line, Tumor; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D008156:Luciferases / Q000235:genetics; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D014162:Transfection
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D008156:Luciferases