A helical oncolytic polypeptide with potent membranolytic activity for cancer therapy

Oncolytic peptides (OLPs) with membranolytic activity show great potential to combat multidrug-resistant cancer cells. Herein, we report a cationic helical oncolytic polypeptide (OLPP) with potent membranolytic activity for cancer therapy. The OLPP was synthesized by ring-opening polymerization of N-carboxyanhydrides (NCAs) and thiol-ene reaction. The OLPP was resistant to protease, showed high cytotoxicity to a series of cancer cells and caused cancer cell necrosis by quickly lysing cancer cell membrane independent of classic death-related intracellular pathways. Intra-tumoral injection of the OLPP effectively suppressed tumor growth in mice through the direct oncolytic effect. The OLPP represents a potential oncolytic chemotherapeutics for cancer therapy.

Automated summary

In this study, a cationic helical oncolytic polypeptide (OLPP) with potent membranolytic activity was synthesized using ring-opening polymerization and thiol-ene reaction. The OLPP showed resistance to protease, high cytotoxicity to cancer cells, and induced cancer cell necrosis by lysing the cancer cell membrane independent of intracellular pathways. Intra-tumoral injection of the OLPP effectively suppressed tumor growth in mice, suggesting its potential as an oncolytic chemotherapeutic for cancer therapy.