HER2-positive breast cancer targeting and treatment by a peptide-conjugated mini nanodrug

Nanomedicine. 2017 Feb;13(2):631-639. doi: 10.1016/j.nano.2016.07.013. Epub 2016 Aug 9.

Abstract

HER2+ breast cancer is one of the most aggressive forms of breast cancer. The new polymalic acid-based mini nanodrug copolymers are synthesized and specifically characterized to inhibit growth of HER2+ breast cancer. These mini nanodrugs are highly effective and in the clinic may substitute for trastuzumab (the marketed therapeutic antibody) and antibody-targeted nanobioconjugates. Novel mini nanodrugs are designed to have slender shape and small size. HER2+ cells were recognized by the polymer-attached trastuzumab-mimetic 12-mer peptide. Synthesis of the nascent cell-transmembrane HER2/neu receptors by HER2+ cells was inhibited by antisense oligonucleotides that prevented cancer cell proliferation and significantly reduced tumor size by more than 15 times vs. untreated control or PBS-treated group. We emphasize that the shape and size of mini nanodrugs can enhance penetration of multiple bio-barriers to facilitate highly effective treatment. Replacement of trastuzumab by the mimetic peptide favors reduced production costs and technical efforts, and a negligible immune response.

Keywords: 8-arm starPEG; HER2+ breast cancer; Polymalic acid; Polymer nanoconjugate; Trastuzumab mimetic peptide.

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Breast Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Humans
  • Nanoparticles / chemistry
  • Peptides / therapeutic use
  • Receptor, ErbB-2*
  • Trastuzumab / administration & dosage
  • Trastuzumab / pharmacokinetics*

Substances

  • Antibodies, Monoclonal, Humanized
  • Peptides
  • Receptor, ErbB-2
  • Trastuzumab