Mitochondria-Targeting Antimicrobial Peptide (AMP) Regulating N6-Methyladenosine (m6A) Modification to Promote Colon Cancer Ferroptosis.

Colon cancer (COAD) is one of the common malignant tumors in the gastrointestinal tract; it is urgent to deeply study the mechanism of COAD and develop new therapeutic agents, which will provide new hope for improving the therapeutic efficacy and prolonging the survival of patients. Mitochondria are crucial organelles that play an important role in COAD, participating in cellular energy and material metabolism and playing a key role in the regulation of cell death, making mitochondria a potential target for COAD therapy. In this study, we designed an antimicrobial peptide (AMP) that can target tumor cells and act on mitochondria. The AMP is taken up by tumor cells and can achieve colocalization with mitochondria, reducing the mitochondrial membrane potential levels in tumor cells and inducing ferroptosis. The AMP affects N6-methyladenosine (m6A) methylation modification in cells and participates in the regulation of ferroptosis. During in vivo experiments on COAD, the AMP demonstrated a strong ability to inhibit tumor growth and good biosafety. Unlike peptide-drug conjugates that rely on toxin release, the synthetic AMP exerts direct targeted activity with improved biosafety and efficiency. The AMP effectively suppresses the development of COAD, providing a new reference method for the treatment of COAD.