Journal
ACS INFECTIOUS DISEASES
Volume 3, Issue 3, Pages 237-248Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.6b00203
Keywords
single-chain polymeric nanoparticles; self-folding; RAFT polymerization; antibiotics; biofilm
Categories
Funding
- UNSW Australia
- Australian Research Council [FT120100096]
- Australian Research Council [FT120100096] Funding Source: Australian Research Council
Ask authors/readers for more resources
Infections caused by multidrug-resistant bacteria are on the rise and, therefore, new antimicrobial agents are required to prevent the onset of a postantibiotic era. In this study, we develop new antimicrobial compounds in the form of single-chain polymeric nanoparticles (SCPNs) that exhibit excellent antimicrobial activity against Gram-negative bacteria (e.g., Pseudomonas aeruginosa) at micromolar concentrations (e.g., 1.4 mu M) and remarkably kill =99.99% of both planktonic cells and biofilm within an hour. Linear random copolymers, which comprise oligoethylene glycol (OEG), hydrophobic, and amine groups, undergo self-folding in aqueous systems due to intramolecular hydrophobic interactions to yield these SCPNs. By systematically varying the hydrophobicity of the polymer, we can tune the extent of cell membrane wall disruption, which in turn governs the antimicrobial activity and rate of resistance acquisition in bacteria. We also show that the incorporation of OEG groups into the polymer design is essential in preventing complexation with proteins in biological medium, thereby maintaining the antimicrobial efficacy of the compound even in in vivo mimicking conditions. In comparison to the last-resort antibiotic colistin, our lead agents have a higher therapeutic index (by ca. 23 times) and hence better biocompatibility. We believe that the SCPNs developed here have potential for clinical applications and the information pertaining to their structureactivity relationship will be valuable toward the general design of synthetic antimicrobial (macro)molecules.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available