Mimics of Host\nDefense Peptides Derived from Dendronized\nPolylysines for Antibacterial and Anticancer Therapy

Bacteria in tumor microenvironments promote carcinogenesis\nand\ntrigger complications, suggesting the significance of intervening\nin bacterial growth in cancer treatment. Here, dendrimer-derived mimics\n(DMs) of host defense peptides (HDPs) were designed for antibacterial\nand anticancer therapy, which feature a dendronized polylysine core\nand polycaprolactone arms. DMs displayed not only remarkable activities\nagainst <i>Staphylococcus aureus</i> and human lung cancer\ncells, but also exceptional selectivity. The membranolytic mechanism\nrevealed by morphology analysis explained their low susceptibility\nto induce resistance. Further, the optimized DM inhibited tumor growth\nin the subcutaneous tumor model when administered <i>via</i> intraperitoneal injection and exhibited negligible toxicity to tissues.\nOverall, we combined the superiority of dendrimers and the mechanism\nfrom HDPs to design agents with dual antibacterial and anticancer\nactivities that possess great potential for clinical oncology therapy.