Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo
Menée in vitro et à l'aide d'une xénogreffe de cancer mammaire sur un modèle murin, cette étude met en évidence l'intérêt de nanoparticules peptidiques capables de se transformer en nanofibrilles au contact des récepteurs HER2 de la tumeur et d'induire l'apoptose des cellules cancéreuses en perturbant la dimérisation de ces récepteurs et les processus de signalisation qui en résultent
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.