Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering , Shenzhen University Health Science Center , Shenzhen 518055 , China.
National Center for NanoScience and Technology , Beijing 100190 , China.
ACS Appl Mater Interfaces. 2019 Dec 11;11(49):45381-45389. doi: 10.1021/acsami.9b15107. Epub 2019 Nov 22.
Nonantibiotic small molecule-modified gold nanoparticles (Au NPs) show great potential as an alternative for commercial antibiotics, yet their narrow antibacterial spectrum hinders the wide application in clinics. We observe that Au NPs cofunctionalized with both bovine serum albumin (BSA) and 4,6-diamino-2-pyrimidinethiol (DAPT) can generate conjugates (Au_DAPT_BSA) with progressive antimicrobial activities, including decreased minimal inhibitory concentration against Gram-negative bacteria and extended antibacterial spectrum against Gram-positive bacteria compared with DAPT-capped Au NPs (Au_DAPT). Au_DAPT_BSA induces no drug resistance and can significantly decrease the number of bacteria in the biofilms formed by and . In addition, Au_DAPT_BSA exhibit in vivo healing efficiency for mice with subcutaneous abscesses caused by clinically isolated, multidrug resistant or without inducing detectable toxicity to the mammalian cells/animals. Our findings provide a new strategy for strengthening nanomaterial-based bactericides such as Au NPs, especially against drug-resistant bacterial infections.
非抗生素小分子修饰的金纳米颗粒(Au NPs)作为商业抗生素的替代品具有巨大的潜力,但它们狭窄的抗菌谱限制了其在临床上的广泛应用。我们观察到,同时用牛血清白蛋白(BSA)和 4,6-二氨基-2-嘧啶硫醇(DAPT)功能化的 Au NPs 可以生成具有渐进式抗菌活性的缀合物(Au_DAPT_BSA),与 DAPT 封端的 Au NPs(Au_DAPT)相比,其对革兰氏阴性菌的最小抑菌浓度降低,对革兰氏阳性菌的抗菌谱扩大。Au_DAPT_BSA 不会诱导耐药性,并且可以显著减少 和 形成的生物膜中的细菌数量。此外,Au_DAPT_BSA 对由临床分离的多药耐药 或 引起的皮下脓肿的小鼠具有体内治疗效果,而对哺乳动物细胞/动物没有可检测到的毒性。我们的研究结果为增强基于纳米材料的杀菌剂(如 Au NPs)提供了一种新策略,特别是针对耐药性细菌感染。