Metal Oxide Doping Modulates the Performances of Copper Oxide Nanoparticular Biocides

Copper has been used as a biocide for more than one century, in various applications. However, as a biocide, copper, both metallic, as a salt or as copper oxide particles, is toxic not only to its intended targets, mainly bacteria and fungi, but also to all living cells. Because of this toxicity, it is desirable to use forms of copper that maximize the required biocidal activity while minimizing the amount of copper that will be released in the environment. Copper oxide nanoparticles are a good compromise for all these requirements. The high surface ratio allows for good reactivity and thus good biocidal activity, while the small amount of copper present in nanoparticles compared to microparticles allows for a limited environmental release. However, plain copper oxide nanoparticles still show significant cytotoxicity, thereby limiting their use. We, therefore, investigated if doping copper oxide nanoparticles with other metal oxide nanoparticles, namely zinc oxide or titanium dioxide, would alter the functional features of the resulting nanoparticles, hopefully increasing the biocidal activity vs. toxicity balance. We investigated biocidal activity by stringent tests using both Staphylococcus aureus and Escherichia coli as target bacteria. In addition, we investigated toxicity on mammalian macrophages or keratinocytes cell lines, as well as on an insect hemocyte cell line. Doping with zinc oxide decreased the biocidal activity, while increasing toxicity, which was the opposite of our expectations. Doping with titanium dioxide decreased the biocidal activity, but also markedly decreased cytotoxicity, which is an interesting avenue to follow. In addition, we also checked that beyond toxicity, the copper oxide-based nanoparticles did not induce an inflammatory reaction, making them safer to use.