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

Journal of the American Chemical Society
Akash GuptaVincent M Rotello

Abstract

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.

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Citations

Nov 22, 2018·Chemical Society Reviews·Akash GuptaVincent M Rotello
Aug 21, 2020·Nature Reviews. Microbiology·Jessa Marie V MakabentaVincent M Rotello
Aug 7, 2020·Biomaterials Science·Qinggele Borjihan, Alideertu Dong
Mar 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yuan ZhouLing Jiang
Jan 23, 2020·Chemistry : a European Journal·Anzhela GalstyanMarcin Stępień
Dec 15, 2020·Advanced Healthcare Materials·Xianzhi ZhangVincent M Rotello
Dec 22, 2019·Nanomedicine : Nanotechnology, Biology, and Medicine·Samson AfewerkiAnderson O Lobo
Jan 12, 2021·Expert Opinion on Drug Delivery·Douweh Leyla Gbian, Abdelwahab Omri
Mar 23, 2019·Journal of Colloid and Interface Science·Youkun ZhengXuemei Wang
May 14, 2021·International Journal of Pharmaceutics·Miguel PalenzuelaRoberto Rosal
Aug 4, 2021·Advanced Healthcare Materials·Qinggele BorjihanYing-Wei Yang
May 29, 2020·Journal of the American Chemical Society·Rui HuangVincent M Rotello
Jan 16, 2020·ACS Applied Materials & Interfaces·Md Anisur RahmanChuanbing Tang
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jessa Marie V MakabentaVincent M Rotello

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