title: Co-delivery of siRNA and hypericin into cancer cells by hyaluronic acid modified PLGA-PEI nanoparticles.
abstract: BACKGROUND
  Malignant tumors cause more death because of the resistance of the hypoxic cancer cell toward radiotherapy. Targeting for hypoxic cancer area and gene silencing to overcome the hypoxia are two kinds of important therapeutic strategies for treating tumors.
  
  
  OBJECTIVE
  In order to explore the combined effects of gene therapy and hypericin (Hy) on tumor cells, hypoxia-inducible factor 1 alpha (HIF-1α) small interfering ribonucleic acid (siRNA) was transfected into the hypoxic human nasopharyngeal carcinoma (CNE2) cells using Hy-encapsulated nanocomplexes (Hy-HPP NPs) as a carrier which would achieve dual targeting to the tumor necrosis area.
  
  
  METHODS
  NPs were prepared by emulsion-diffusion-evaporation method. Formulations were evaluated by conducting in vitro physicochemical studies, electrophoresis, in vivo study, and biochemical studies.
  
  
  CONCLUSIONS
  Hy-loaded nanoparticles with a mean size of around 160 nm was able to enhance the accumulation in the tumors by enhanced permeability and retention effect. The electrophoresis confirmed the good stability of siRNA/Hy-HPP NPs in the presence of phosphate-buffered saline (pH 7.4), competitive heparin, and RNase. The results of transfection showed that the uptake of siRNA was significantly increased up to 50% in CNE2 cells. The level of the HIF-1α with Hy-encapsulated nanocomplexes was significantly reduced to 30% in the transfected CNE2 cells. In vivo studies, the carrier exhibited higher intensity at the tumor tissue cells and higher affinity toward the necrotic tumor tissue.
  
  
  CONCLUSIONS
  Results demonstrated that Hy-HPP NPs could significantly enhance the tranfection efficiency of siRNA, suggesting Hy-encapsulated nanoparticle as an efficient gene carrier. The co-delivery of HIF-1α siRNA (siHIF-1α) and Hy could efficiently decrease the level of HIF-1α and increase the affinity toward necrotic tissues. Hence, this is a promising strategy for further application in radiotherapy.
authors.affiliation: a Department of Pharmaceutics , State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University , Nanjing , China .
authors.forename: Yanan
authors.initials: Y
authors.lastname: Li
authors.affiliation: b Department of Oncology , Subei People's Hospital , Yangzhou , China , and.
authors.forename: Junling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: b Department of Oncology , Subei People's Hospital , Yangzhou , China , and.
authors.forename: Buhai
authors.initials: B
authors.lastname: Wang
authors.affiliation: a Department of Pharmaceutics , State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University , Nanjing , China .
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: c Department of Pharmacy , Institute of Medical Sciences, Batna Elhadj Lakhdar University , Batna , Algeria.
authors.forename: Ammar
authors.initials: A
authors.lastname: Ouahab
mesh_terms: D000873:Anthracenes; D002277:Carcinoma; D045744:Cell Line, Tumor; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007097:Imines / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010316:Particle Size; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D011095:Polyethylenes / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D014162:Transfection / Q000379:methods
chemical_list: D000873:Anthracenes; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007097:Imines; D011091:Polyesters; D011095:Polyethylenes; D034741:RNA, Small Interfering; C523703:poly(L-lactide-co-glycolide-co-epsilon-caprolactone); C505405:poly(ethylene imine); D010569:Perylene; C004965:hypericin; D006820:Hyaluronic Acid
keywords: Co-delivery; HIF-1α; hyaluronic acid; hypericin; siRNA; targeted delivery