title: Near-infrared-light-based nano-platform boosts endosomal escape and controls gene knockdown in vivo.
abstract: Current nanoparticle-based gene delivery techniques face two major limitations, namely, endosomal degradation and poor cytosolic release of the nanoparticles and nonspecificity of treatment. These limitations can be overcome with certain light-based techniques, such as photochemical internalization to enable endosomal escape of the delivered nanoparticles and light-controlled gene expression to overcome the nonspecific effects. However, these techniques require UV/visible light, which is either phototoxic and/or has low tissue penetration capabilities, thus preventing their use in deep tissues in a clinical setting. In an effort to overcome these barriers, we have successfully demonstrated a light-based gene delivery system that significantly boosts cytosolic gene delivery, with precise control over gene expression and the potential for use in nonsuperficial tissues. Core-shell fluorescent upconversion nanoparticles excited by highly penetrating near-infrared radiation and emitting simultaneously in the ultraviolet and visible ranges were synthesized and used as remote nanotransducers to simultaneously activate endosomal escape and gene knockdown. Gene knockdown using photomorpholinos was enhanced as much as 30% in vitro compared to the control without endosomal escape facilitation. A similar trend was seen in vivo in a murine melanoma model, demonstrating the enormous clinical potential of this system.
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, National University of Singapore , 117576 Singapore.
authors.forename: Muthu Kumara Gnanasammandhan
authors.initials: MK
authors.lastname: Jayakumar
authors.forename: Akshaya
authors.initials: A
authors.lastname: Bansal
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.forename: Risheng
authors.initials: R
authors.lastname: Yao
authors.forename: Bing Nan
authors.initials: BN
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002470:Cell Survival; D003600:Cytosol / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005456:Fluorescent Dyes / Q000737:chemistry; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D008027:Light; D008422:Materials Testing; D008545:Melanoma / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared; D014466:Ultraviolet Rays
chemical_list: D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species