pH-Sensitive Zwitterionic Polymer as an Antimicrobial Agent with Effective Bacterial Targeting.

It is highly desirable to develop new and more potent biocompatible antimicrobial agents to reduce the increasing risk of bacterial infection worldwide. To address this problem, we prepared a smart pH-sensitive polymer, poly(N'-citraconyl-2-(3-aminopropyl-N,N-dimethylammonium)ethyl methacrylate), or P(CitAPDMAEMA), which can undergo change in functionality from a biocompatible zwitterionic polymer to an antimicrobial cationic polymer at acidic bacterial infection sites. The precursor polymer, poly(2-(3-aminopropyl-N,N-dimethylammonium)ethyl methacrylate) (P(APDMAEMA)), was first prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization, and then modified with citraconic anhydride to obtain the zwitterionic P(CitAPDMAEMA). P(CitAPDMAEMA) is zwitterionic at physiological pH and exhibits low hemotoxicity and good biocompatibility. However, P(CitAPDMAEMA) can change from neutral to cationic with decreasing pH because of the hydrolysis of citraconic amide under low pH conditions. This switch leads to pronounced bacteria binding of cationic P(CitAPDMAEMA) under acidic conditions of the infection sites and significantly inhibits the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). These results indicate that P(CitAPDMAEMA) is potentially a new on-demand antimicrobial agent.