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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Human epidermal growth factor receptor 2 (HER2) overexpression is common in breast cancer, driving tumor growth and survival.
• Current treatments for HER2-positive breast cancer often require combination therapies due to high HER2 expression levels.

Purpose of the Study:

• To design novel, non-toxic transformable peptides for targeted HER2 therapy.
• To investigate the mechanism of peptide-induced disruption of HER2 dimerization and downstream signaling.

Main Methods:

• Design of peptides that self-assemble into micelles and transform into nanofibrils upon binding to HER2.
• In vitro assessment of HER2 dimerization inhibition and induction of apoptosis.
• In vivo evaluation of therapeutic efficacy in mouse xenograft models of HER2-positive breast cancer.

Main Results:

• Peptides specifically targeted HER2-expressing cancer cells, undergoing a phase transformation from micelles to nanofibrils.
• HER2 dimerization and downstream signaling pathways were effectively inhibited, leading to cancer cell apoptosis.
• The transformable peptides demonstrated significant efficacy as a monotherapy in preclinical HER2-positive breast cancer models.

Conclusions:

• Transformable peptides offer a novel strategy for targeted HER2-positive breast cancer therapy.
• This peptide-based approach effectively inhibits HER2 signaling and induces cancer cell death, potentially as a standalone treatment.