title: Efficient targeted gene delivery by a novel PAMAM/DNA dendriplex coated with hyaluronic acid.
abstract: OBJECTIVE
  To design and develop a novel target-specific DNA-delivery system using hyaluronic acid (HA)-polyamidoamine (PAMAM) conjugates (P-HA).
  
  
  METHODS
  The coupling of HA to the PAMAM dendrimer was analyzed by (1)H-NMR and elemental analysis (CHN). Their properties were characterized in terms of size and zeta-potential and evaluated for in vitro and in vivo transfection efficiency.
  
  
  RESULTS
  The designed covalent HA-dendriplexes enhanced gene transfection of pCMV-Luc reporter gene in overexpressing CD44-receptor cancer cells. They were also more efficient in transfecting MDA-MB231 cells than conventional PEI-polyplexes. The cytotoxicity of the covalent HA-dendriplexes was lower than when using conventional polyethylenimine-polyplexes. In vivo studies showed that these targeted complexes were also efficient for delivering pCMVLuc in different organs of healthy mice, as well as in tumors of C57BL/6 animals.
  
  
  CONCLUSIONS
  The HA-dendriplexes developed in this work may offer an advantageous alternative to conventional cationic polymer-based formulations for DNA delivery into cancer cells in an efficient and safe manner.
authors: Department of Pharmacy & Pharmaceutical Technology, School of Pharmacy, University of Navarra, C/Irunlarrea 1, 31080 Pamplona, Spain.
authors: Koldo
authors: K
authors: Urbiola
authors: Carmen
authors: C
authors: Sanmartín
authors: Laura
authors: L
authors: Blanco-Fernández
authors: Conchita
authors: C
authors: Tros de Ilarduya
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D050091:Dendrimers / Q000737:chemistry*; D005260:Female; D017930:Genes, Reporter; D018960:Hyaluronan Receptors / Q000235:genetics; D006820:Hyaluronic Acid / Q000737:chemistry*; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000235:genetics; D011073:Polyamines / Q000737:chemistry*; D014162:Transfection
chemical_list: D050091:Dendrimers; D018960:Hyaluronan Receptors; C531249:Poly(amidoamine); D011073:Polyamines; D006820:Hyaluronic Acid; D004247:DNA; D008156:Luciferases
keywords: gene therapy; gene transfer; hyaluronic acid/hyaluronan; nanoparticle; nanotechnology; polyamidoamine dendrimer