title: Non-viral vectors based on magnetoplexes, lipoplexes and polyplexes for VEGF gene delivery into central nervous system cells.
abstract: Nanotechnology based non-viral vectors hold great promise to deliver therapeutic genes into the central nervous system (CNS) in a safe and controlled way. Vascular endothelial growth factor (VEGF) is a potential therapeutic gene candidate for CNS disorders due to its specific roles in brain angiogenesis and neuroprotection. In this work, we elaborated three different non-viral vectors based on magnetic, cationic lipid and polymeric nanoparticles complexed to the phVEGF165aIRESGFP plasmid, which codifies the VEGF protein -extracellular- and the green fluorescent protein (GFP) -intracellular-. Nanoparticles and corresponding nanoplexes -magnetoplexes, lipoplexes and polyplexes- were characterized in terms of size, zeta potential, polydispersity index, morphology and ability to bind, release and protect DNA. Transfection efficiencies of nanoplexes were measured in terms of percentage of GFP expressing cells, mean fluorescent intensity (MFI) and VEGF (ng/ml) production in HEK293, C6 and primary neuronal culture cells. Magnetoplexes showed the highest transfection efficiencies in C6, followed by lipoplexes, and in primary neuronal culture cells, followed by polyplexes. Lipoplexes were the most efficient in HEK293 cells, followed by magnetoplexes. The biological activity of VEGF was confirmed by its proliferative effect in HUVEC cells. Overall, these results provide new insights for VEGF gene delivery into CNS cells using non-viral vectors.
authors.affiliation: NanoBioCel Group, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Ilia
authors.initials: I
authors.lastname: Villate-Beitia
authors.affiliation: NanoBioCel Group, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Puras
authors.affiliation: Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Neuroprothesis and Neuroengineering Research Group, Miguel Hernandez University, Elche, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Soto-Sánchez
authors.affiliation: NanoBioCel Group, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Agirre
authors.affiliation: NanoBioCel Group, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Edilberto
authors.initials: E
authors.lastname: Ojeda
authors.affiliation: NanoBioCel Group, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain.
authors.forename: Jon
authors.initials: J
authors.lastname: Zarate
authors.affiliation: Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain; Neuroprothesis and Neuroengineering Research Group, Miguel Hernandez University, Elche, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernández
authors.affiliation: NanoBioCel Group, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Spain. Electronic address: joseluis.pedraz@ehu.eus.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Pedraz
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004339:Drug Compounding; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008055:Lipids; C086724:Lipofectamine; D058185:Magnetite Nanoparticles; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: CNS; Gene delivery; Non-viral vectors; VEGF