Esterase-Activated Charge-Reversal Polymer for Fibroblast-Exempt Cancer Gene Therapy

Adv Mater. 2016 Dec;28(48):10613-10622. doi: 10.1002/adma.201603095. Epub 2016 Oct 27.

Abstract

Selective gene expression in tumors via responsive dissociation of polyplexes triggered by intracellular signals is demonstrated. An esterase-responsive charge-reversal polymer mediates selective gene expression in the cancer cells high in esterases over fibroblasts low in esterase activity. Its gene therapy with the TRAIL suicide gene effectively induces apoptosis of HeLa cells but does not activate fibroblasts to secrete WNT16B, enabling potent cancer gene therapy with few side effects.

Keywords: cancer gene therapy; charge-reversal polymer; esterase-responsive; fibroblast exempt; intraperitoneal tumors.

MeSH terms

  • Apoptosis / genetics
  • Esterases / metabolism*
  • Fibroblasts* / enzymology
  • Fibroblasts* / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Genes, Transgenic, Suicide / genetics
  • Genetic Therapy*
  • HeLa Cells
  • Humans
  • Neoplasms / enzymology
  • Neoplasms / genetics*
  • Neoplasms / therapy*
  • Polymers / chemistry*
  • Wnt Proteins / metabolism

Substances

  • Polymers
  • WNT16 protein, human
  • Wnt Proteins
  • Esterases