Engineered Polymer Nanoparticles with Unprecedented Antimicrobial Efficacy and Therapeutic Indices against Multidrug-Resistant Bacteria and Biofilms.
Engineered Polymer Nanoparticles with Unprecedented Antimicrobial Efficacy and Therapeutic Indices against Multidrug-Resistant Bacteria and Biofilms.
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具有前所未有的抗菌功效和针对多药耐药细菌和生物膜的治疗指标的工程聚合物纳米颗粒。
DOI：
10.1021/jacs.8b06961
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发表时间：
2018-09-26
影响因子：
15
通讯作者：
Rotello VM
中科院分区：
文献类型：
--
作者：
Gupta A;Landis RF;Li CH;Schnurr M;Das R;Lee YW;Yazdani M;Liu Y;Kozlova A;Rotello VM
耐抗生素细菌“超级细菌”的迅速出现，伴随着治疗失败和高死亡率，对全球健康构成严重威胁。抗生素耐药生物膜产生的慢性感染使超级细菌的风险进一步加剧，这些生物膜使它们对现有的治疗难以治愈。我们假设，通过在合成的半刚性聚合物支架中精心设计疏水和阳离子结构域，可以镜像和放大抗菌肽的属性，从而产生有效的抗菌药物。我们报告了具有高效抗菌性能的聚合物纳米颗粒的创建。这些纳米颗粒清除生物膜，对哺乳动物细胞毒性低，对红细胞具有前所未有的治疗指标。最值得注意的是，细菌对这些纳米颗粒的耐药性在连续传代20次后未被观察到，与临床相关抗生素仅在几次传代后就出现明显耐药性形成鲜明对比。
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 semi-rigid 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 towards 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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影响因子：
6.2
作者：
Gabriel GJ;Madkour AE;Dabkowski JM;Nelson CF;Nüsslein K;Tew GN
通讯作者：
Tew GN
影响因子：
4.3
作者：
Kuroda, Kenichi;Caputo, Gregory A.;DeGrado, William F.
通讯作者：
DeGrado, William F.
影响因子：
15
作者：
Ilker, MF;Nüsslein, K;Coughlin, EB
通讯作者：
Coughlin, EB
DOI：
10.1126/science.1182395
发表时间：
2010-01-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Harris SR;Feil EJ;Holden MT;Quail MA;Nickerson EK;Chantratita N;Gardete S;Tavares A;Day N;Lindsay JA;Edgeworth JD;de Lencastre H;Parkhill J;Peacock SJ;Bentley SD
通讯作者：
Bentley SD
影响因子：
2.1
作者：
Gupta, Akash;Saleh, Neveen M.;Rotello, Vincent M.
通讯作者：
Rotello, Vincent M.