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Antimicrobial polymers exhibit great potential for treating drug-resistant bacteria; however, designing antimicrobial polymers that can selectively kill bacteria and cause relatively low toxicity to normal tissues/cells remains a key challenge. Here, we report a pH window for ionizable polymers that exhibit high selectivity toward bacteria. Ionizable polymer PC6A showed the greatest selectivity (131.6) at pH 7.4, exhibiting low hemolytic activity and high antimicrobial activity against bacteria, whereas a very high or low protonation degree (PD) produced relatively low selectivity (≤35.6). Bactericidal mechanism of PC6A primarily comprised membrane lysis without inducing drug resistance even after consecutive incubation for 32 passages. Furthermore, PC6A demonstrated synergistic effects in combination with antibiotics at pH 7.4. Hence, this study provides a strategy for designing selective antimicrobial polymers.

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