A Photoactivatable AIE Polymer for Light-Controlled Gene Delivery: Concurrent Endo/Lysosomal Escape and DNA Unpacking

Angew Chem Int Ed Engl. 2015 Sep 21;54(39):11419-23. doi: 10.1002/anie.201503640. Epub 2015 Jun 19.

Abstract

Endo/lysosomal escape of gene vectors and the subsequent unpacking of nucleic acids in cytosol are two major challenges for efficient gene delivery. Herein, we report a polymeric gene delivery vector, which consists of a photosensitizer (PS) with aggregation-induced emission (AIE) characteristics and oligoethylenimine (OEI) conjugated via an aminoacrylate (AA) linker that can be cleaved by reactive oxygen species (ROS). In aqueous media, the polymer could self-assemble into bright red fluorescent nanoparticles (NPs), which can efficiently bind to DNA through electrostatic interaction for gene delivery. Upon visible light irradiation, the generated ROS can break the endo/lysosomal membrane and the polymer, resulting in light-controlled endo/lysosomal escape and unpacking of DNA for efficient gene delivery. The smart polymer represents the first successful gene vector to simultaneously address both challenges with a single light excitation process.

Keywords: aggregation-induced emission; endo/lysosomes; gene delivery; polymers; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • Endosomes / metabolism*
  • Gene Transfer Techniques*
  • HeLa Cells
  • Humans
  • Light*
  • Lysosomes / metabolism*
  • Nanoparticles
  • Photochemical Processes*
  • Polymers / chemistry*
  • Reactive Oxygen Species / metabolism
  • Static Electricity

Substances

  • Polymers
  • Reactive Oxygen Species
  • DNA