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

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