Department of Chemistry and Biochemistry , University of Hull , Hull HU6 7RX , U.K.
Department of Chemistry, College of Science , University of Babylon , Hilla , Iraq.
ACS Appl Mater Interfaces. 2019 Apr 3;11(13):12232-12243. doi: 10.1021/acsami.8b21862. Epub 2019 Mar 20.
Copper oxide nanoparticles (CuONPs) have been widely recognized as good antimicrobial agents but are heavily regulated due to environmental concerns of their postuse. In this work, we have developed and tested a novel type of formulation for copper oxide (CuONPs) which have been functionalized with (3-glycidyloxypropyl)trimethoxysilane (GLYMO) to allow further covalent coupling of 4-hydroxyphenylboronic acid (4-HPBA). As the boronic acid (BA) groups on the surface of CuONPs/GLYMO/4-HPBA can form reversible covalent bonds with the diol groups of glycoproteins on the bacterial cell surface, they can strongly bind to the cells walls resulting in a very strong enhancement of their antibacterial action which is not based on electrostatic adhesion. Scanning electron microscopy and transmission electron microscopy imaging revealed that 4-HPBA-functionalized CuO nanoparticles could accumulate more on the cell surface than nonfunctionalized ones. We demonstrate that the CuONPs with boronic acid surface functionality are far superior antibacterial agents compared to bare CuONPs. Our results showed that the antibacterial impact of the 4-HPBA-functionalized CuONPs on Rhodococcus rhodochrous and Escherichia coli is 1 order of magnitude higher than that of bare CuONPs or CuONPs/GLYMO. We also observed a marked increase of the 4-HPBA-functionalized CuONPs antibacterial action on these microorganisms at shorter incubation times compared with the bare CuONPs at the same conditions. Significantly, we show that the cytotoxicity of CuONPs functionalized with 4-HPBA as an outer layer can be controlled by the concentration of glucose in the media, and that the effect is reversible as glucose competes with the sugar residues on the bacterial cell walls for the BA-groups on the CuONPs. Our experiments with human keratinocyte cell line exposure to CuONPs/GLYMO/4-HPBA indicated lack of measurable cytotoxicity at particle concentration which are effective as an antibacterial agent for both R. rhodochrous and E. coli. We envisage that formulations of CuONPs/GLYMO/4-HPBA can be used to drastically reduce the overall CuO concentration in antimicrobial formulations while strongly increasing their efficiency.
氧化铜纳米颗粒（CuONPs）已被广泛认为是良好的抗菌剂，但由于对其使用后环境的关注，其受到了严格的监管。在这项工作中，我们开发并测试了一种新型氧化铜（CuONPs）制剂，该制剂已用（3-缩水甘油氧基丙基）三甲氧基硅烷（GLYMO）功能化，以允许进一步共价偶联 4-羟基苯硼酸（4-HPBA）。由于 CuONPs/GLYMO/4-HPBA 表面上的硼酸（BA）基团可以与细菌细胞表面上糖蛋白的二醇基团形成可逆的共价键，因此它们可以强烈结合到细胞壁上，从而大大增强了它们的抗菌作用，而不是基于静电粘附。扫描电子显微镜和透射电子显微镜成像显示，4-HPBA 功能化的 CuO 纳米颗粒可以比非功能化的纳米颗粒更多地在细胞表面积累。我们证明，具有硼酸表面功能的 CuONPs 比裸 CuONPs 具有优越的抗菌性能。我们的结果表明，与裸 CuONPs 或 CuONPs/GLYMO 相比，4-HPBA 功能化的 CuONPs 对红球菌和大肠杆菌的抗菌作用高出 1 个数量级。我们还观察到，与相同条件下的裸 CuONPs 相比，在较短的孵育时间内，4-HPBA 功能化的 CuONPs 对这些微生物的抗菌作用明显增强。值得注意的是，我们表明，作为外层的 4-HPBA 功能化的 CuONPs 的细胞毒性可以通过培养基中葡萄糖的浓度来控制，并且由于葡萄糖与细胞壁上的糖残基竞争 BA 基团，因此这种作用是可逆的。我们用人类角质形成细胞系暴露于 CuONPs/GLYMO/4-HPBA 的实验表明，在对 R. rhodochrous 和 E. coli 均有效的作为抗菌剂的颗粒浓度下，没有可测量的细胞毒性。我们设想，CuONPs/GLYMO/4-HPBA 的制剂可以大大降低抗菌制剂中氧化铜的总体浓度，同时大大提高其效率。
