Transformation from Hydrophilic Yet Membrane-Inactive Linear Chain Polymers to Membrane-Active Nanoantibiotics

Area of Science:

• Biochemistry
• Materials Science
• Nanotechnology

Background:

• Amphipathic membrane-active antimicrobials (MAAs) show promise against antimicrobial resistance (AMR).
• Clinical use of MAAs is limited by their toxicity to mammalian cells due to non-specific hydrophobic interactions.

Purpose of the Study:

• To develop novel biocompatible antimicrobial agents that selectively target bacterial membranes.
• To overcome the toxicity challenges associated with traditional MAAs.

Main Methods:

• Assembly of hydrophilic linear polymers into star-shaped nanostructures.
• Utilizing multivalent interactions to induce membrane topological transitions and pore formation.
• Testing efficacy against bacterial strains, including AMR strains, and assessing mammalian cell toxicity.

Main Results:

• Star-shaped polymers with critical multivalency (e.g., 6-arms) effectively pinch and form pores in microbial membranes.
• Selective disruption of bacterial membranes with minimal toxicity to mammalian cells.
• Demonstrated efficacy against clinical antimicrobial resistance (AMR) strains.

Conclusions:

• Hydrophilic star-shaped polymers offer a facile and effective blueprint for novel antimicrobial agents.
• This strategy selectively targets bacteria, including AMR strains, by exploiting membrane curvature and multivalency.
• The developed MAAs present a low-toxicity alternative for combating bacterial infections.