Improving NK1R-targeted gene delivery of stearyl-antimicrobial peptide CAMEL by conjugating it with substance P

Bioorg Med Chem Lett. 2020 Aug 15;30(16):127353. doi: 10.1016/j.bmcl.2020.127353. Epub 2020 Jun 15.

Abstract

Specificity is a crucial condition that hampers the application of non-viral vectors for cancer gene therapy. In a previous study, we developed an efficient gene vector, stearyl-CAMEL, using N-terminal stearylation of the antimicrobial peptide CAMEL. Substance P (SP), an 11-residue neuropeptide, rapidly enters cells after binding to the neurokinin-1 receptor (NK1R), which is expressed in many cancer cell lines. In this study, the NK1R-targeted gene vector stearyl-CMSP was constructed by conjugating SP to the C-terminus of stearyl-CAMEL. Our results indicated that stearyl-CMSP displayed significant transfection specificity for NK1R-expressing cells compared with that shown by stearyl-CAMEL. Accordingly, the stearyl-CMSP/p53 plasmid complexes had significantly higher antiproliferative activity against HEK293-NK1R cells than they did against HEK293 cells, while the stearyl-CAMEL/p53 plasmid complexes did not show this specificity in antiproliferative activity. Consequently, conjugation of the NK1R-targeted ligand SP is a simple and successful strategy to construct efficient cancer-targeted non-viral gene vectors.

Keywords: Antimicrobial peptide; Cancer gene therapy; NK1R-targeted gene delivery; Non-viral gene vector; Substance P.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Transfer Techniques*
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • HEK293 Cells
  • Humans
  • Molecular Structure
  • Pore Forming Cytotoxic Proteins / chemistry
  • Pore Forming Cytotoxic Proteins / metabolism*
  • Receptors, Neurokinin-1 / genetics*
  • Receptors, Neurokinin-1 / metabolism
  • Substance P / chemistry
  • Substance P / metabolism*

Substances

  • Pore Forming Cytotoxic Proteins
  • Receptors, Neurokinin-1
  • Substance P