title: Gene delivery nanoparticles to modulate angiogenesis.
abstract: Angiogenesis is naturally balanced by many pro- and anti-angiogenic factors while an imbalance of these factors leads to aberrant angiogenesis, which is closely associated with many diseases. Gene therapy has become a promising strategy for the treatment of such a disordered state through the introduction of exogenous nucleic acids that express or silence the target agents, thereby engineering neovascularization in both directions. Numerous non-viral gene delivery nanoparticles have been investigated towards this goal, but their clinical translation has been hampered by issues associated with safety, delivery efficiency, and therapeutic effect. This review summarizes key factors targeted for therapeutic angiogenesis and anti-angiogenesis gene therapy, non-viral nanoparticle-mediated approaches to gene delivery, and recent gene therapy applications in pre-clinical and clinical trials for ischemia, tissue regeneration, cancer, and wet age-related macular degeneration. Enhanced nanoparticle design strategies are also proposed to further improve the efficacy of gene delivery nanoparticles to modulate angiogenesis.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center and Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Jayoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Mirando
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Aleksander S
authors.initials: AS
authors.lastname: Popel
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center and Institute for Nanobiotechnology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Departments of Ophthalmology, Neurosurgery, and Materials Science & Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: green@jhu.edu.
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Green
mesh_terms: D000818:Animals; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics
keywords: Age-related macular degeneration; Chitosan; Cholesterol; Gene therapy; Ischemia; N-[1-(2.3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate; Non-viral; Poly(beta-amino ester); Poly(ethylene imine); Poly(l-lysine); Poly(lactic-co-glycolic) acid; Poly(vinyl pyrrolidone)-cyclodextrin; Polymeric nanoparticles; Tissue engineering; Tumor; Wound healing