Engineered Polymer Nanoparticles with Unprecedented Antimicrobial Efficacy and Therapeutic Indices against Multidrug-Resistant Bacteria and Biofilms

The rapid emergence of antibiotic-resistant bacterial “superbugs” with concomitant treatment failure and high mortality rates presents a severe threat to global health. The superbug risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that render them refrac...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2018-09, Vol.140 (38), p.12137-12143
Main Authors: Gupta, Akash, Landis, Ryan F, Li, Cheng-Hsuan, Schnurr, Martin, Das, Riddha, Lee, Yi-Wei, Yazdani, Mahdieh, Liu, Yuanchang, Kozlova, Anastasia, Rotello, Vincent M
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - chemical synthesis
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - toxicity
Biofilms - drug effects
Enterobacter cloacae - drug effects
Erythrocytes - drug effects
Escherichia coli - drug effects
Humans
Methicillin-Resistant Staphylococcus aureus - drug effects
Mice
Microbial Sensitivity Tests
Nanoparticles - chemistry
Nanoparticles - toxicity
NIH 3T3 Cells
Polymers - chemical synthesis
Polymers - chemistry
Polymers - pharmacology
Polymers - toxicity
Pseudomonas aeruginosa - drug effects
Quaternary Ammonium Compounds - chemical synthesis
Quaternary Ammonium Compounds - chemistry
Quaternary Ammonium Compounds - pharmacology
Quaternary Ammonium Compounds - toxicity
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Summary:The rapid emergence of antibiotic-resistant bacterial “superbugs” with concomitant treatment failure and high mortality rates presents a severe threat to global health. The superbug risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that render them refractory to available treatments. We hypothesized that efficient antimicrobial agents could be generated through careful engineering of hydrophobic and cationic domains in a synthetic semirigid polymer scaffold, mirroring and amplifying attributes of antimicrobial peptides. We report the creation of polymeric nanoparticles with highly efficient antimicrobial properties. These nanoparticles eradicate biofilms with low toxicity to mammalian cells and feature unprecedented therapeutic indices against red blood cells. Most notably, bacterial resistance toward these nanoparticles was not observed after 20 serial passages, in stark contrast to clinically relevant antibiotics where significant resistance occurred after only a few passages.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.8b06961