Developing Potent and Selective Anticancer Therapy through Chemical Approaches and the Combination of Cationic Amphipathic Oncolytic Peptides

This study explores the structure–activity relationships of cationic amphipathic Mastoparan AF derivatives and their combination with the oncolytic peptide LTX315 to enhance the anticancer efficacy. The original peptide was modified to improve its selective interaction with cancer cell membranes, thereby increasing anticancer potency while minimizing hemolytic activity. Circular dichroism spectroscopy and molecular dynamics simulations were employed to evaluate structural changes and self-association tendencies. Among the derivatives, MAF-10L exhibited superior anticancer activity but elevated hemolysis, which was mitigated through combination therapy with LTX315. These findings underscore the potential of cationic amphipathic peptides as a basis for selective anticancer treatments and highlight the benefits of peptide combinations in reducing adverse effects while enhancing the therapeutic efficacy.