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Strongly Enhanced Antibacterial Action of Copper Oxide Nanoparticles with Boronic Acid Surface Functionality

Halbus, Ahmed F.; Horozov, Tommy S.; Paunov, Vesselin N.


Ahmed F. Halbus

Vesselin N. Paunov


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.


Halbus, A. F., Horozov, T. S., & Paunov, V. N. (2019). Strongly Enhanced Antibacterial Action of Copper Oxide Nanoparticles with Boronic Acid Surface Functionality. ACS Applied Materials & Interfaces, 11(13), 12232-12243.

Journal Article Type Article
Acceptance Date Mar 8, 2019
Online Publication Date Mar 20, 2019
Publication Date Mar 20, 2019
Deposit Date Mar 24, 2019
Publicly Available Date Mar 21, 2020
Journal ACS Applied Materials & Interfaces
Print ISSN 1944-8244
Electronic ISSN 1944-8252
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 11
Issue 13
Pages 12232-12243
Keywords General Materials Science; Nanotechnology; Microbiology; Antimicrobials
Public URL
Publisher URL


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Copyright Statement
This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials & Interfaces, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see<br />

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