Intracellular sequestration of HER2 via targeted subcellular peptide delivery

Abstract

The use of peptides in drug development has been hampered by their poor pharmaceutical properties, most notably their inability to reliably permeate biological membranes and lack of targeting. To overcome these disadvantages, the AMino acid Intracellular Delivery SysTem (AMIDST) was developed. This modular peptide-based delivery system confers cellular permeability and organelle-specific targeting for therapeutic peptides. As demonstrated in this study, the delivery of a HER2-binding peptide to the secretory organelles of breast cancer cells resulted in intracellular sequestration, a reduction in downstream signalling, and reduced viability compared to the delivery of a control peptide. Given its modular design and ease of production, AMIDST has the potential to enhance the use of peptides as therapeutic agents.

Keywords:

• Peptide
• HER2
• ErbB2
• endoplasmic reticulum
• golgi apparatus
• membrane translocation

Acknowledgements

Authors thank Dr. David Roane for support and encouragement.

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

The authors would like to acknowledge the Research Development Committee and the Gatton College of Pharmacy at East Tennessee State University for supporting this work.