A Multifunctional Peptide-Conjugated AIEgen for Efficient and Sequential Targeted Gene Delivery into the Nucleus

Angew Chem Int Ed Engl. 2019 Apr 1;58(15):5049-5053. doi: 10.1002/anie.201901527. Epub 2019 Mar 8.

Abstract

Gene therapy has immense potential as a therapeutic approach to serious diseases. However, efficient delivery and real-time tracking of gene therapeutic agents have not been solved well for successful gene-based therapeutics. Herein we present a versatile gene-delivery strategy for efficient and visualized delivery of therapeutic genes into the targeted nucleus. We developed an integrin-targeted, cell-permeable, and nucleocytoplasmic trafficking peptide-conjugated AIEgen named TD NCP for the efficient and sequential targeted delivery of an antisense single-stranded DNA oligonucleotide (ASO) and tracking of the delivery process into the nucleus. As compared with TD NCP/siRNA-NPs (siRNA functions mainly in the cytoplasm), TD NCP/ASO-NPs (ASO functions mainly in the nucleus) exhibited a better interference effect, which further indicates that TD NCP is a nucleus-targeting vector. Moreover, TD NCP/ASO-NPs showed a favorable tumor-suppressive effect in vivo.

Keywords: AIE luminogens; antisense oligonucleotides; gene delivery; multifunctional peptides; nucleus targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Nucleus / genetics*
  • Fluorescent Dyes / chemistry*
  • Gene Transfer Techniques*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Oligonucleotides / genetics*
  • Peptides / chemistry*

Substances

  • Fluorescent Dyes
  • Oligonucleotides
  • Peptides