Department of Chemistry , University of Massachusetts Amherst , 710 North Pleasant Street , Amherst , Massachusetts 01003 , United States.
Faculty of Chemistry and Geoscience , Ruprecht-Karls-University , Im Neuenheimer Feld 234 , 69120 Heidelberg , Germany.
J Am Chem Soc. 2018 Sep 26;140(38):12137-12143. doi: 10.1021/jacs.8b06961. Epub 2018 Sep 13.
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.
具有抗药性的细菌“超级细菌”迅速出现，导致治疗失败和高死亡率，这对全球健康构成了严重威胁。慢性感染产生的抗生素耐药生物膜进一步加剧了超级细菌的风险，使它们对现有治疗方法产生抗药性。我们假设通过在合成半刚性聚合物支架中仔细设计疏水性和阳离子域，可以产生有效的抗菌剂，从而模仿和放大抗菌肽的特性。我们报告了具有高效抗菌性能的聚合物纳米粒子的创建。这些纳米粒子能够消除生物膜，对哺乳动物细胞的毒性低，并且具有针对红细胞的前所未有的治疗指数。最值得注意的是，在 20 次连续传代后，没有观察到细菌对这些纳米粒子的耐药性，而在临床相关抗生素中，仅经过几次传代就出现了明显的耐药性。
