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Silver nanoparticles exert toxic effects in human monocytes and macrophages associated with the disruption of Δψm and release of pro-inflammatory cytokines

  • Inorganic Compounds
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Abstract

Silver nanoparticles (AgNP) are the most widely produced type of nanoparticles due to their antimicrobial and preservative properties. However, their systemic bioavailability may be considered a potential hazard. When AgNP reach the bloodstream, they interact with the immune cells, contributing to the onset and development of an inflammatory response. Monocytes and macrophages play a pivotal role in our defense system, but the interaction of AgNP with these cells is still not clear. Therefore, the main objective of this work was to assess the cytotoxic and pro-inflammatory effects induced by 5, 10, and 50 nm AgNP coated with polyvinylpyrrolidone (PVP) and citrate, in concentrations that could be attained in vivo (0–25 μg/mL), in human monocytes isolated from human blood and human macrophages derived from a monocytic cell line (THP-1). The effects of PVP and citrate-coated AgNP on cell viability, mitochondrial membrane potential, and cytokines release were evaluated. The results evidenced that AgNP exert strong harmful effects in both monocytes and macrophages, through the establishment of a strong pro-inflammatory response that culminates in cell death. The observed effects were dependent on the AgNP concentration, size and coating, being observed more pronounced cytotoxic effects with smaller PVP coated AgNP. The results showed that human monocytes seem to be more sensitive to AgNP exposure than human macrophages. Considering the increased daily use of AgNP, it is imperative to further explore the adverse outcomes and mechanistic pathways leading to AgNP-induced pro-inflammatory effects to deep insight into the molecular mechanism involved in this effect.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors gratefully acknowledge the medical and the nursing staff of the Centro Hospitalar do Porto-Hospital de Santo António Blood Bank for their collaboration in the recruitment of blood donors to participate in the study.

Funding

The present work was supported with funding from FCT/MCTES through national funds and ‘Programa Operacional Competitividade e Internacionalização (COMPETE) (PTDC/NAN-MAT/29248/2017-POCI‑01‑0145‑FEDER‑029248). Adelaide Sousa thanks FCT (Fundação para a Ciência e Tecnologia) and ESF (European Social Fund) through POCH (Programa Operacional Capital Humano) for her PhD grant reference SFRH/BD/150656/2020. Ana T Rufino acknowledges her researcher contract to FCT under the project PTDC/MED-QUI/29243/201 Marisa Freitas acknowledges her contract under the Scientific Employment Stimulus—Individual Call (CEEC Individual) 2020.04126.CEECIND. Marisa Freitas also thanks LAQV-REQUIMTE for her contract under the reference LA/P/0008/2020. The authors acknowledge the support of the i3S Scientific Platform HEMS, member of the national infrastructure PPBI - Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122).

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Authors and Affiliations

  1. LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira No. 228, 4050-313, Porto, Portugal

    Adelaide Sousa, Ana T. Rufino, Eduarda Fernandes & Marisa Freitas

  2. Histology and Electron Microscopy (HEMS), Instituto de Investigação e Inovação em Saúde i3S, Instituto de Biologia Molecular e Celular BMC, Universidade Do Porto, Porto, Portugal

    Rui Fernandes & Ana Malheiro

  3. UCIBIO, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050‑313, Porto, Portugal

    Félix Carvalho

  4. Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Porto, Portugal

    Félix Carvalho

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  1. Adelaide Sousa
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Correspondence to Eduarda Fernandes or Marisa Freitas.

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All patient-related procedures and protocols were performed in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Centro Hospitalar do Porto. Written informed consent was obtained from all participants.

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Sousa, A., Rufino, A.T., Fernandes, R. et al. Silver nanoparticles exert toxic effects in human monocytes and macrophages associated with the disruption of Δψm and release of pro-inflammatory cytokines. Arch Toxicol 97, 405–420 (2023). https://doi.org/10.1007/s00204-022-03415-x

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