Computational Screening and Identification of Novel Cell-penetrating Peptides for Effective Drug Delivery

Effectively delivering anti-cancer drugs remains a significant challenge in oncology due to their non-specific distribution and harmful side effects. Cellpenetrating peptides (CPPs) offer a promising solution by enabling the targeted transport of therapeutic agents, such as proteins, nucleic acids, and small molecules, directly into cancer cells. Bacterial-derived peptides have shown unique stability and penetration efficiency, making them strong candidates for further development. However, challenges such as low stability in the bloodstream and off-target effects limit their clinical potential. To address these issues, we used a computational screening approach and selected 59 candidates. We refined our selection to five promising peptides through further computational analysis based on their predicted ability to interact with cell membranes. These five peptides were chemically synthesized and tested in human cancer cells. Our computational and experimental approaches identified novel CPPs that can efficiently penetrate human cancer cells.