Due to their high tunability, Antimicrobial polymers (APs) have emerged as promising materials to tackle challenges associated with antimicrobial resistance (AMR).1 However, traditional APs consist of cationic and hydrophobic units, which result in inherent toxicity due to their amphiphilicity nature2, 3. Herein, a non-amphiphilic APs were developed and investigated. This platform combined cationic monomers with hydrophilic units capable of forming hydrogen bonds. The rationale behind the design is that non-amphiphilic APs remain isolated in solution until they come into contact with negatively charged bacterial membranes, where they start attracting each other and cluster through hydrogen bonds. This approach allows for enhanced local concentration of polymers to disrupt bacterial membranes while reducing unspecific toxicity associated with hydrophobicity. Minimal inhibitory concentration (MIC) and hemotoxicity tests revealed that a subset of polymers exhibited significant antibacterial activity with little to no effect on mammalian cells, particularly when the cationic charge and specific subunit ratio were balanced at 50:50. This study emphasizes that hydrophobicity is not an essential quality in APs, presenting non-amphiphilic polymers as new motif for AP designs4.
Reference
1. Pham, P.; Oliver, S.; Boyer, C., Design of Antimicrobial Polymers. Macromolecular Chemistry and Physics 2023, 224 (3), 2200226.
2. Jain, A.; Duvvuri, L. S.; Farah, S.; Beyth, N.; Domb, A. J.; Khan, W., Antimicrobial Polymers. Advanced Healthcare Materials 2014, 3 (12), 1969-1985.
3. Ergene, C.; Yasuhara, K.; Palermo, E. F., Biomimetic antimicrobial polymers: recent advances in molecular design. Polymer Chemistry 2018, 9 (18), 2407-2427.
4. Bapolisi, A. M.; Lehnen, A.-C.; Wolff, M.; Kramer, J.; Kogikoski, S.; Steinbrecher, R.; Michler, N.; Kiesow, A.; Bald, I.; Obry, M.; Kersting, S.; Stensitzki, T.; Müller-Werkmeister, H. M.; Leiske, M. N.; Chiantia, S.; Hartlieb, M. Non‐Amphiphilic Antimicrobial Polymers. Angewandte Chemie International Edition 2025, DOI: 10.1002/anie.202507564.