Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo

Lu Zhang, Di Jing, Nian Jiang, Tatu Rojalin, Christopher M. Baehr, Dalin Zhang, Wenwu Xiao, Yi Wu, Zhaoqing Cong, Jian Jian Li, Yuanpei Li, Lei Wang, Kit S. Lam

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Human epidermal growth factor receptor 2 (HER2) is overexpressed in >20% of breast cancers. Dimerization of HER2 receptors leads to the activation of downstream signals enabling the proliferation and survival of malignant phenotypes. Owing to the high expression levels of HER2, combination therapies are currently required for the treatment of HER2+ breast cancer. Here, we designed non-toxic transformable peptides that self-assemble into micelles under aqueous conditions but, on binding to HER2 on cancer cells, transform into nanofibrils that disrupt HER2 dimerization and subsequent downstream signalling events leading to apoptosis of cancer cells. The phase transformation of peptides enables specific HER2 targeting, and inhibition of HER2 dimerization blocks the expression of proliferation and survival genes in the nucleus. We demonstrate, in mouse xenofraft models, that these transformable peptides can be used as a monotherapy in the treatment of HER2+ breast cancer.

Original languageEnglish (US)
Pages (from-to)145-153
Number of pages9
JournalNature Nanotechnology
Volume15
Issue number2
DOIs
StatePublished - Feb 1 2020

ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrical and Electronic Engineering

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    Zhang, L., Jing, D., Jiang, N., Rojalin, T., Baehr, C. M., Zhang, D., Xiao, W., Wu, Y., Cong, Z., Li, J. J., Li, Y., Wang, L., & Lam, K. S. (2020). Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo. Nature Nanotechnology, 15(2), 145-153. https://doi.org/10.1038/s41565-019-0626-4