Alkaline phosphatase-responsive peptide amphiphiles promote the apoptosis of HER2-positive breast cancer cells via enhanced drug delivery

High expression of human epidermal growth factor receptor 2 (HER2) accelerates the proliferation of breast cancer cells and the progression and malignancy of breast cancer. HER2-positive breast cancer cells often overexpress antiapoptotic proteins, enabling them to resist apoptosis despite the presence of proapoptotic signals. Additionally, traditional chemotherapeutic drugs are easily eliminated from tumor cells, preventing them from reaching concentrations adequate for effectively destroying tumors or inhibiting tumor growth. In this research, these obstacles were addressed by developing a drug delivery system based on the amphipathic peptide Pep1. The model chemotherapeutic drugs doxorubicin (DOX) and curcumin (CUR) are encapsulated by Pep1 (DC/Pep1) to form spherical nanoparticles, which are ultimately converted to nanofibers by alkaline phosphatase (ALP) to increase drug accumulation in SKBR3 cells. Compared with DC/Pep2, which cannot undergo a morphological transformation, DC/Pep1 increases the expression of E-cadherin and pro-Caspase-3 and inhibits the migration and accelerates the apoptosis of HER2-positive breast cancer cells. Morphologically transformable amphipathic peptides, as drug carriers that target HER2-positive breast cancer cells, represent a facile and promising strategy for breast cancer therapy.