(203) Quaternary amine-based helical polypeptides prime anticancer immunity and facilitate gene delivery

Cancer immunotherapy mainly targets immune checkpoint blockade, but limitations include restricted applicability, resistance, and systemic toxicity. Immunogenic cell death promotes neoantigen recognition by DAMPs such as CRT, HMGB1, and ATP. Traditional ICD inducers rely on ROS or ER stress but show high cytotoxicity and limited immune modulation. Polypeptide, with distinct secondary structures, offer potential advantages. Our prior study showed fluorinated polypeptides induce ICD via mitochondrial depolarization, yet the role of backbone structure versus side-chain chemistry remains unclear.