Doxorubicin-Poly-<scp>l</scp>-lysine Peptide Polymers: A Rapid, Selective, and Biocompatible Therapeutic for Infection and Cancer Prevention

The intricate relationship between infection and cancer, particularly the heightened susceptibility to infection in patients with compromised immune systems due to the toxicity of conventional chemotherapy, poses significant challenges, such as prolonging recovery and escalating financial burdens. Therefore, integrating antimicrobial activity while concurrently enhancing biocompatibility is crucial for advancing traditional anticancer agents. In this study, we developed a series of biocompatible peptide polymers with dual antimicrobial and anticancer functions through a facile, drug-initiated polymerization approach. These peptide polymers demonstrated rapid action and greater selectivity for tumor cells and Gram-positive pathogens over normal cells compared with free doxorubicin. Multiple mechanisms, including membrane disruption, induction of cell necrosis, and nuclear-dominated intracellular distribution, were revealed for the peptide polymers. These results collectively suggest a low propensity for inducing drug resistance. Overall, these peptide polymers combine the merits of conventional anticancer agents and antimicrobial peptide mimics, offering a promising strategy for anticancer drug development and clinical oncology applications.