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We hypothesized that certain surface functionalizations of CuO NPs may render NPs toxic to bacteria, but still be relatively harmless to human cells. To control this hypothesis, the toxicity of differently functionalized CuO NPs to bacteria\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    vs human cells (THP-1 macrophages and HACAT keratinocytes) was compared using similar conditions and end points. CuO NPs functionalized with polyethylene glycol (CuO\u2013PEG), carboxyl (CuO\u2013COOH, anionic), ammonium (CuO\u2013NH\n                    <jats:sub>4<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    , cationic) and unfunctionalized CuO NPs and CuSO\n                    <jats:sub>4<\/jats:sub>\n                    (controls) were tested. In general, the toxicity of Cu compounds decreased in the following order: CuO\u2013NH\n                    <jats:sub>4<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    \u2009&gt;\u2009unfunctionalized CuO\u2009&gt;\u2009CuSO\n                    <jats:sub>4<\/jats:sub>\n                    \u2009&gt;\u2009CuO\u2013COOH\u2009&gt;\u2009CuO\u2013PEG. Positively charged unfunctionalized CuO and especially CuO\u2013NH\n                    <jats:sub>4<\/jats:sub>\n                    <jats:sup>+<\/jats:sup>\n                    proved most toxic (24-h EC\n                    <jats:sub>50<\/jats:sub>\n                    =\u00a021.7\u201347\u00a0mg\/l) and had comparable toxicity to bacterial and mammalian cells. The multivariate analysis revealed that toxicity of these NPs was mostly attributed to their positive zeta potential, small hydrodynamic size, high Cu dissolution, and induction of reactive oxygen species (ROS) and TNF-\u03b1. In contrast, CuO\u2013COOH and CuO\u2013PEG NPs had lower toxicity to human cells compared to bacteria despite efficient uptake of these NPs by human cells. In addition, these NPs did not induce TNF-\u03b1 and ROS. Thus, by varying the NP functionalization and Cu form (soluble salt vs NPs), it was possible to \u201ctarget\u201d the toxicity of Cu compounds, whereas carboxylation and PEGylation rendered CuO NPs that were more toxic to bacteria than to human cells envisaging their use in medical antibacterial products.\n                  <\/jats:p>","DOI":"10.1007\/s00204-020-02720-7","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T22:02:12Z","timestamp":1586210532000},"page":"1561-1573","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Surface carboxylation or PEGylation decreases CuO nanoparticles\u2019 cytotoxicity to human cells in vitro without compromising their antibacterial properties"],"prefix":"10.1007","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2026-5340","authenticated-orcid":false,"given":"Anna-Liisa","family":"Kubo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2608-536X","authenticated-orcid":false,"given":"Grigory","family":"Vasiliev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5779-9851","authenticated-orcid":false,"given":"Heiki","family":"Vija","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9279-1839","authenticated-orcid":false,"given":"Jekaterina","family":"Krishtal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6271-7993","authenticated-orcid":false,"given":"Vello","family":"T\u00f5ugu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0028-7083","authenticated-orcid":false,"given":"Meeri","family":"Visnapuu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9765-055X","authenticated-orcid":false,"given":"Vambola","family":"Kisand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4944-4900","authenticated-orcid":false,"given":"Anne","family":"Kahru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8767-1365","authenticated-orcid":false,"given":"Olesja M.","family":"Bondarenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,7]]},"reference":[{"key":"2720_CR1","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1177\/1091581813487563","volume":"32","author":"S Alarifi","year":"2013","unstructured":"Alarifi S, Ali D, Verma A et al (2013) Cytotoxicity and genotoxicity of copper oxide nanoparticles in human skin keratinocytes cells. 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