title: Enhanced small interfering RNA delivery into cells by exploiting the additive effect between photo-sensitive peptides and targeting ligands.
abstract: OBJECTIVE
  To enhance the targeting delivery efficiency of small interfering RNA (siRNA) to tumour cells, a novel multifunctional liposome (PSP/NGR-L) comodified with photo-sensitive cell-penetrating peptides (PSP) and asparagine-glycine-arginine peptide (NGR) was constructed and investigated.
  
  
  METHODS
  PSP was conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-maleimide(polyethylene glycol)-2000 (DSPE-PEG2000 -MAL) to generate DSPE-PEG2000 -PSP and used to form PSP/NGR-L, the features of the liposomes were determined. HT-1080 and MCF-7 cells were used for cellular uptake tests, and the cellular uptake pathways were identified. Intracellular trafficking and endosomal escape were also evaluated. In-vitro siRNA transfection evaluations were carried out in HT-1080 cells.
  
  
  RESULTS
  The encapsulation efficiencies of liposomes were about 80%, and the mean particle sizes were around 100 nm. The targeting specificity of PSP/NGR-L was significantly enhanced via NGR navigation and ultraviolet (UV) light illumination. The internalization of PSP/NGR-L in HT-1080 cells was mediated by more than one cellular uptake mechanisms. The constructed nanocarrier could escape from the endosome to produce its effects in the cellular cytoplasm with the help of UV illumination. PSP/NGR-L could down-regulate expression of c-myc and augmented cell apoptosis in HT-1080 cells.
  
  
  CONCLUSIONS
  The application of combined PSP and NGR modifications may be a new approach for the selectively targeted delivery of siRNA to cancer cells.
authors.affiliation: Department of Clinical Laboratory, Huangshi Love & Health Hospital of Hubei Province, Huangshi, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.affiliation: Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D003593:Cytoplasm / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008024:Ligands; D008081:Liposomes / Q000737:chemistry; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry*
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D008024:Ligands; D008081:Liposomes; C526428:NGR peptide; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols
keywords: NGR-targeted; cell-penetrating peptides; photo-sensitive cell-penetrating peptides (PSP); small interfering RNA