New ToxAtlas provides insights into cellular responses to inhaled nanomaterials

A new international study led by Prof. Herbert B. Schiller and Dr. Tobias Stöger at the DZL site CPC-M, with substantial contributions from Dr. Carola Voss, first author of the study and Principal Investigator at the DZL site BREATH in Hannover, provides important new insights into how inhaled nanomaterials trigger inflammatory processes in the lung. The work, entitled “Toward a ToxAtlas of Carbon-Based Nanomaterials: Single-Cell RNA Sequencing Reveals Initiating Cell Circuits in Pulmonary Inflammation”, was published in ACS Nano and resulted from close collaboration among researchers from Germany, Denmark, Switzerland, and the United Kingdom. In addition to Carola Voss, Svenja Gaedcke, another scientist from BREATH, contributed to the study, along with numerous researchers from other sites of the German Center for Lung Research (DZL).

The team employed state-of-the-art single-cell RNA sequencing to investigate the early cellular responses of the lung to different carbon-based nanomaterials, including spherical carbon nanoparticles as well as single-walled and multi-walled carbon nanotubes. The aim was to identify which cell types and molecular signaling pathways initiate the inflammatory response. To capture the very earliest cellular events, mouse lungs were analyzed as early as twelve hours after exposure to the nanomaterials.

The results clearly demonstrate that chemically similar but structurally distinct nanomaterials activate different inflammatory programs. Spherical particles (CNPs) primarily stimulate alveolar epithelial cells, which release pro-inflammatory cytokines such as CXCL1 and GM-CSF, promoting the recruitment of neutrophils without causing overt cell damage. In contrast, fibrous carbon nanotubes (CNTs) induce pronounced tissue damage in epithelial and immune cells and lead to the release of so-called alarmins, including IL-1α and IL-33, thereby triggering a strong and potentially chronic inflammatory response. Notably, the study also reveals early activation of mesenchymal cells, particularly lipofibroblasts located in close proximity to alveolar type II cells. These cells emerge as key regulatory hubs that critically influence both the magnitude and the quality of the inflammatory response.

“To improve accessibility of our findings, we developed the web-based ToxAtlas, an interactive tool that visualizes cell-type-specific gene expression patterns and signaling pathways induced by different nanomaterials,” explains Carola Voss. “This provides the research community with a systematic resource to link material properties to biological effects and supports the development of safer, animal-free testing strategies.”

Original publication:

Voss C, Han L, Ansari M, Strunz M, Haefner V, Angelidis I, Mayr CH, Berthing T, Zhou Q, Guenther EM, Huzain O, Schmid O, Vogel U, Gote-Schniering J, Gaedcke S, Theis FJ, Schiller HB, Stoeger T. Toward a ToxAtlas of Carbon-Based Nanomaterials: Single-Cell RNA Sequencing Reveals Initiating Cell Circuits in Pulmonary Inflammation. ACS Nano. 2025 Nov 18;19(45):39139-39156. doi: 10.1021/acsnano.5c12054. Epub 2025 Nov 3. PMID: 41183169; PMCID: PMC12632174.

 

Text: BREATH/AB

Foto: MHH/Schweigler

BREATH-PI Dr. Carola Voss