Enhanced anticancer efficacy of Pa-MAP 1.9 peptide-coated silver nanostars on breast cancer cells.

Breast cancer remains a major global health challenge due to its rising incidence and the limitations of conventional chemotherapeutic options. Antimicrobial peptides (AMPs) with dual antimicrobial and anticancer activities have emerged as promising alternatives; however, their clinical application is limited by issues such as stability, selectivity, and delivery. Nanocarrier systems, particularly silver nanostars (AgNSs), can address these challenges by improving peptide delivery and cellular interaction. This study explores the nanocomplex AgNSs-Pa-MAP 1.9 as a combinatory therapeutic platform against breast cancer. AgNSs-Pa-MAP 1.9 exhibited enhanced anticancer effects against both hormone-dependent (MCF-7) and hormone-independent (MDA-MB-231) breast cancer cells, with higher sensitivity observed in MDA-MB-231 cells. Selectivity analysis indicated moderate preferential cytotoxicity toward cancer cells compared to non-tumorigenic MCF-10A cells. Biophysical and cellular assessments revealed subtype-dependent morphological and mechanical alterations, including changes in cell area, surface roughness, and elasticity, with more pronounced effects in cancer cells. Compared to free Pa-MAP 1.9, AgNSs-Pa-MAP 1.9 showed a concentration-dependent therapeutic window with preferential activity against breast cancer cells, particularly MDA-MB-231, supporting its potential as a nanoplatform for further development in targeted cancer therapy.