title: A promising targeted gene delivery system: folate-modified dexamethasone-conjugated solid lipid nanoparticles.
abstract: BACKGROUND
  Non-viral gene delivery could deliver drugs/genes through cellular membranes and nuclear membranes by some modification of materials.
  
  
  OBJECTIVE
  This study develops a kind of vector to target the cells through receptor-mediated pathways. Nuclear localization signal (NLS) was also used to increase the nuclear uptake of genetic materials.
  
  
  METHODS
  A lipid containing dexamethasone (Dexa) was synthesized as the material of the preparation of solid lipid nanoparticles (SLNs) and folate (Fa)-conjugated PEG-PE (Fa-PEG-PE) ligands were used to modify the SLNs. The in vitro cytotoxicity of the carriers at various concentrations (10, 20, 50, 100, and 200 μg/ml) were evaluated in KB human carcinoma cells (KB cells). In vivo transfection efficiency of the novel modified vectors was evaluated in disseminated peritoneal tumors on mice bearing KB cells.
  
  
  RESULTS
  Fa-PEG-PE modified SLNs/enhanced green fluorescence protein plasmid (pEGFP) has a particle size of 258 nm, and the gene loading quantity of the vector was 90%. The in vitro cytotoxicity of Fa-PEG-PE-modified SLNs/pEGFP (Fa-SLNs/pEGFP) was low (cell viabilities were between 80% and 100% compared with controls). Fa-SLNs/pEGFP displayed remarkably higher transfection efficiency (40%) than non-modified SLNs/pEGFP (24%) and the vectors not containing Dexa (30%) in vivo.
  
  
  CONCLUSIONS
  The results demonstrate that Fa and Dexa could function as excellent active targeting ligands to improve the cell targeting and nuclear targeting ability of the carriers and the resulting vectors could be promising active targeting drug/gene delivery systems.
authors.affiliation: Department of Chinese Medicine Integrated Traditional Chinese Medicine and Western Medicine and.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Linfu
authors.initials: L
authors.lastname: Ge
authors.forename: Ximin
authors.initials: X
authors.lastname: Liu
authors.forename: Fansheng
authors.initials: F
authors.lastname: Kong
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage*; D005492:Folic Acid / Q000008:administration & dosage* / Q000235:genetics; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007624:KB Cells; D008055:Lipids / Q000008:administration & dosage* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D008055:Lipids; D003907:Dexamethasone; D005492:Folic Acid
keywords: Active targeted; folate-PEG-PE; gene therapy; nuclear localization