Hybrid Anticancer Peptide Synergistically Improving Cancer Cell Uptake and Inducing Apoptosis Mediated by Membrane Fusion

Anticancer peptides (ACPs) have exhibited tremendous potential in tumor treatment. However, low peptide delivery efficiency limits some ACPs' clinical application. Herein, we designed a hybrid peptide named AFP-KLA and investigated the tumor cell-specific targeting ability and proapoptotic properties. Our results revealed that AFP peptides primarily facilitated the selective binding of KLA peptides to tumor cell membranes, enabling the whole peptides to enter the cells via membrane fusion. Furthermore, AFP-KLA demonstrated superior colocalization within MCF-7 cells and induced cell apoptosis by disrupting the mitochondrial membrane. Subsequently, we constructed a tumor model subcutaneously in mice and tested the antitumor activity of the designed ACP in vivo. We observed that AFP-KLA could effectively inhibit tumor growth and displayed excellent antitumor activity. In summary, these results suggest that AFP-KLA is possibly a promising therapeutic agent for targeted therapy of breast cancer and can guide the future design of ACPs.