Systemic Delivery of Helical Polypeptide Induces Tumor-Specific Apoptosis

Abstract

A cationic helical peptide (CHP) has been intensively used as a gene or drug delivery carrier, and as antibiotics for therapeutic purposes in biomedical fields. CHPs are insufficient as delivery systems because they have a short chain length giving rise to a low helical propensity. In an effort to resolve these inherent limitations, artificial cationic helical polypeptides (ACHP) have been recently devised by further modifications of the side chains in functional group-bearing polypeptides. ACHP possess higher cell-penetrating property than conventional cell-penetrating peptides. However, these ACHP do not possess specificity toward diseases and penetrates into cells indiscriminately like their predecessors. To address these limitations, we have added pH-sensitive anion-donating groups to a helical polypeptide enable the peptide to selectively penetrate into tumors through pH-dependent formational change of peptide following exposure to acidic tumor microenvironment. The mitochondriadestabilizing helical polypeptide undergoing pH-dependent conformational transitions led to efficient targeting of tumors and disruption of mitochondrial membranes, thus leading to tumorspecific induction of apoptosis. This work presents a promising peptide therapeutic system for cancer therapy.