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Surface carboxylation or PEGylation decreases CuO nanoparticles' cytotoxicity to human cells in vitro without compromising their antibacterial properties.

ABSTRACT: Clinical use of CuO nanoparticles (NPs) as antibacterials can be hampered by their toxicity to human cells. 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 Escherichia coli vs human cells (THP-1 macrophages and HACAT keratinocytes) was compared using similar conditions and end points. CuO NPs functionalized with polyethylene glycol (CuO-PEG), carboxyl (CuO-COOH, anionic), ammonium (CuO-NH4+, cationic) and unfunctionalized CuO NPs and CuSO4 (controls) were tested. In general, the toxicity of Cu compounds decreased in the following order: CuO-NH4+?>?unfunctionalized CuO?>?CuSO4?>?CuO-COOH?>?CuO-PEG. Positively charged unfunctionalized CuO and especially CuO-NH4+ proved most toxic (24-h EC50 = 21.7-47 mg/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-?. In contrast, CuO-COOH and CuO-PEG 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-? and ROS. Thus, by varying the NP functionalization and Cu form (soluble salt vs NPs), it was possible to "target" 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.

SUBMITTER: Kubo AL

PROVIDER: S-EPMC7261733 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Surface carboxylation or PEGylation decreases CuO nanoparticles' cytotoxicity to human cells in vitro without compromising their antibacterial properties.

Kubo Anna-Liisa AL Vasiliev Grigory G Vija Heiki H Krishtal Jekaterina J Tõugu Vello V Visnapuu Meeri M Kisand Vambola V Kahru Anne A Bondarenko Olesja M OM

Archives of toxicology 20200407 5

Clinical use of CuO nanoparticles (NPs) as antibacterials can be hampered by their toxicity to human cells. 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 Escherichia coli vs human cells (THP-1 macrophages and HACAT keratinocytes) was compared using similar conditions and end points. CuO NPs functionalize ...[more]

PMID: 32253467

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Project description:BACKGROUND:Copper oxide (CuO) nanomaterials are used in a wide range of industrial and commercial applications. These materials can be hazardous, especially if they are inhaled. As a result, the pulmonary effects of CuO nanomaterials have been studied in healthy subjects but limited knowledge exists today about their effects on lungs with allergic airway inflammation (AAI). The objective of this study was to investigate how pristine CuO modulates allergic lung inflammation and whether surface modifications can influence its reactivity. CuO and its carboxylated (CuO COOH), methylaminated (CuO NH3) and PEGylated (CuO PEG) derivatives were administered here on four consecutive days via oropharyngeal aspiration in a mouse model of AAI. Standard genome-wide gene expression profiling as well as conventional histopathological and immunological methods were used to investigate the modulatory effects of the nanomaterials on both healthy and compromised immune system. RESULTS:Our data demonstrates that although CuO materials did not considerably influence hallmarks of allergic airway inflammation, the materials exacerbated the existing lung inflammation by eliciting dramatic pulmonary neutrophilia. Transcriptomic analysis showed that CuO, CuO COOH and CuO NH3 commonly enriched neutrophil-related biological processes, especially in healthy mice. In sharp contrast, CuO PEG had a significantly lower potential in triggering changes in lungs of healthy and allergic mice revealing that surface PEGylation suppresses the effects triggered by the pristine material. CONCLUSIONS:CuO as well as its functionalized forms worsen allergic airway inflammation by causing neutrophilia in the lungs, however, our results also show that surface PEGylation can be a promising approach for inhibiting the effects of pristine CuO. Our study provides information for health and safety assessment of modified CuO materials, and it can be useful in the development of nanomedical applications.

Dataset Information

Surface carboxylation or PEGylation decreases CuO nanoparticles' cytotoxicity to human cells in vitro without compromising their antibacterial properties.

Publications

Surface carboxylation or PEGylation decreases CuO nanoparticles' cytotoxicity to human cells in vitro without compromising their antibacterial properties.

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