Gene delivery nanoparticles to modulate angiogenesis

Jayoung Kim; Adam C Mirando; Aleksander S Popel; Jordan J Green

doi:10.1016/j.addr.2016.11.003

Gene delivery nanoparticles to modulate angiogenesis

Adv Drug Deliv Rev. 2017 Sep 15:119:20-43. doi: 10.1016/j.addr.2016.11.003. Epub 2016 Nov 30.

Authors

Jayoung Kim¹, Adam C Mirando², Aleksander S Popel², Jordan J Green³

Affiliations

¹ 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.
² 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.
³ 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.

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.

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.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Gene Transfer Techniques
Genetic Therapy / methods
Humans
Nanoparticles / administration & dosage*
Neoplasms / drug therapy
Neoplasms / genetics
Neovascularization, Pathologic / drug therapy*
Neovascularization, Pathologic / genetics

Abstract

Publication types

MeSH terms

Grants and funding