title: Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization.
abstract: The controlled delivery of nucleic acids to selected tissues remains an inefficient process mired by low transfection efficacy, poor scalability because of varying efficiency with cell type and location, and questionable safety as a result of toxicity issues arising from the typical materials and procedures employed. High efficiency and minimal toxicity in vitro has been shown for intracellular delivery of nuclei acids by using nanoneedles, yet extending these characteristics to in vivo delivery has been difficult, as current interfacing strategies rely on complex equipment or active cell internalization through prolonged interfacing. Here, we show that a tunable array of biodegradable nanoneedles fabricated by metal-assisted chemical etching of silicon can access the cytosol to co-deliver DNA and siRNA with an efficiency greater than 90%, and that in vivo the nanoneedles transfect the VEGF-165 gene, inducing sustained neovascularization and a localized sixfold increase in blood perfusion in a target region of the muscle.
authors.affiliation: 1] Department of Materials, Imperial College London, London, SW6 7PB, UK [2] Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London, SW6 7PB, UK.
authors.forename: C
authors.initials: C
authors.lastname: Chiappini
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA.
authors.forename: E
authors.initials: E
authors.lastname: De Rosa
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA.
authors.forename: J O
authors.initials: JO
authors.lastname: Martinez
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: 1] Department of Materials, Imperial College London, London, SW6 7PB, UK [2] Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London, SW6 7PB, UK.
authors.forename: J
authors.initials: J
authors.lastname: Steele
authors.affiliation: 1] Department of Materials, Imperial College London, London, SW6 7PB, UK [2] Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London, SW6 7PB, UK.
authors.forename: M M
authors.initials: MM
authors.lastname: Stevens
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA.
authors.forename: E
authors.initials: E
authors.lastname: Tasciotti
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D049329:Nanostructures; D009339:Needles; D018919:Neovascularization, Physiologic; D010957:Plasmids / Q000235:genetics / Q000494:pharmacology; D012825:Silicon; D014162:Transfection / Q000295:instrumentation / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D012825:Silicon
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