Predicting the morphology-driven pathogenicity of nanofibers through proteomic profiling
Open accessAbstract
The shape and durability of inhalable fibers is connected with their potential to cause lung cancer. Especially toxicological effects of nanofibers and their derivatives are still incompletely understood. Currently, their safety evaluation is performed under in vivo settings. However, as nanofiber applications continue to expand, alternative approaches are urgently needed that align with the 3 R principles (Replacement, Reduction, Refinement). To this end, silicon carbide (SiC) and titanium dioxide (TiO 2 ) nanofibers as well as their ground fragments were tested in the NR8383 alveolar macrophage assay. Intact nanofibers induced dose-dependent cytotoxicity, oxidative stress, and the release of pro-inflammatory cytokines, while their ground counterparts elicited minimal effects. The subsequent proteomic profiling of cells exposed to a sub-cytotoxic nanofiber concentration revealed significant alterations in the levels of 32 % (SiC) and 8 % (TiO 2 ) of all detected proteins compared to untreated cells. Besides protein modifications induced by oxidative stress, key alterations comprised protein clusters attributed to inflammation (n proteins =9), vesicular trafficking (n = 22), metabolic changes (n = 32) and apoptosis (n = 5). Cells treated with equal amounts of ground nanofibers exhibited only negligible changes, highlighting the morphology-driven nature of the effects. Finally, a set of 58 proteins are proposed as a proteomic fingerprint of nanofiber-related toxicity at the cellular level. Overall, the study substantiates fiber morphology-driven effects of nanofibers in alveolar macrophages and outlines concrete protein biomarkers to describe nanofiber pathogenicity along with underlying mechanisms. This work contributes to the development of a robust in vitro testing strategy required for the Safe-and-Sustainable-by-Design demand of the European Commission.
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Strong correlations between fibre properties and adverse health effects have been reported for a wide variety of fibre materials.
“Observations of strong correlations between fibre properties and adverse health effects have been reported for a wide variety of fibre materials [14–16],”
From Macrophages bend long fibres with flexural rigidity lower than 3 mN·nm2 to avoid frustrated phagocytosis (2026) · cites this paper as [16]
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Stobernack, T., Vennemann, A., Ribalta, C., Schendel, J., Gräb, O., Ledwith, R., Pink, M., Haase, A., Wiemann, M., & Dumit, V. I. (2026) · Small · doi:10.1002/smll.202510530 · Cited by 4 · see citing works
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- Authors
- Stobernack, T., Vennemann, A., Broßell, D., Gräb, O., Pink, M., Haase, A., Wiemann, M., & Dumit, V. I.
- Affiliations
- German Federal Institute for Risk Assessment (BfR) (DE)
- Federal Institute for Occupational Safety and Health (DE)
- Corresponding author
- Wiemann, Martin
- Dumit, Verónica I.
- ORCID
- Venue
- Nano Today
- Publisher
- Elsevier BV
- Published
- 2025-12
- Volume
- 65
- Pages
- 102812
- ISSN
- 1748-0132 (ISSN-L)
- OpenAlex
- W4410842349
- Cited by
- 5
- References
- 54
- Citations by year
- 2026: 5
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nano Today (publishedVersion, cc-by)
- Refubium (Universitätsbibliothek der Freien Universität Berlin) (submittedVersion, cc-by)
- OpenAgrar (submittedVersion, cc-by)
- Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver (cc-by)
- Funders
- Bundesministerium für Bildung und Forschung (03XP0216)
- German Federal Institute for Risk Assessment
- Horizon Europe (953183)
- Horizon 2020 Framework Programme (1322\u2013777)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Occupational and environmental lung diseases
- Physical Sciences › Materials Science › Materials Chemistry › Nanoparticles: synthesis and applications
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- nanofibers, fiber morphology, nanoparticle toxicity, silicon carbide nanofibers, titanium dioxide nanofibers, alveolar macrophages, proteomic profiling, protein biomarkers, oxidative stress, inflammation, vesicle trafficking, apoptosis, in vitro toxicity testing, 3Rs, safe-by-design, lung cancer risk
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