2. Academic Validation
  3. Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo

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

  • Nat Nanotechnol. 2020 Feb;15(2):145-153. doi: 10.1038/s41565-019-0626-4.
Lu Zhang # 1,  Di Jing # 1,  Nian Jiang 2 3,  Tatu Rojalin 1,  Christopher M Baehr 1,  Dalin Zhang 1,  Wenwu Xiao 1,  Yi Wu 1,  Zhaoqing Cong 1,  Jian Jian Li 2,  Yuanpei Li 1,  Lei Wang 4,  Kit S Lam 5 6
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Medicine, UC Davis NCI-designated Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA.
  • 2 Department of Radiation Oncology, School of Medicine, University of California Davis, Sacramento, CA, USA.
  • 3 Department of Oncology, Xiangya Hospital, Central South University, Hunan, China.
  • 4 CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, China. wanglei@nanoctr.cn.
  • 5 Department of Biochemistry and Molecular Medicine, UC Davis NCI-designated Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA. kslam@ucdavis.edu.
  • 6 Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, USA. kslam@ucdavis.edu.
  • # Contributed equally.
PMID: 31988501 DOI: 10.1038/s41565-019-0626-4
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.

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