Using cutting-edge single-cell RNA sequencing, the research team examined the early cellular reactions of lung tissues exposed to various carbon-based nano materials including soot-like spherical carbon nano particles and fiber-like single- and multi-walled carbon nano tubes.
The goal? To pinpoint which specific cell types and molecular pathways kickstart inflammation after nano materials enter the lungs. To capture these very first cellular responses, the scientists analyzed mouse lungs just 12 hours after exposure.
Key Findings: Structure Matters More Than Chemistry
The results reveal that chemically similar but structurally different nano materials trigger distinct inflammatory pathways:
- Spherical Carbon Particles (CNP)
These activate alveolar epithelial cells, which release pro-inflammatory signaling molecules (cytokines). This recruits neutrophils (a type of immune cell) without causing significant cell damage.
- Fibrous Nano-tubes (CNT)
In contrast, tubular carbon nano tubes damage both epithelial and immune cells, leading to the release of alarm signals like IL-1α and IL-33. This triggers a strong, sometimes chronic inflammatory response.
An additional surprise: Mesenchymal cells, particularly lipofibroblasts near alveolar Type II cells, play a central role in shaping the intensity and nature of the inflammatory reaction.
A New Tool for Safer Nano materials: Introducing ToxAtlas
To make these findings widely accessible, the team developed ToxAtlas - an interactive online platform that maps cell-type-specific gene expression patterns and signaling pathways for different nano materials. Researchers can now connect material properties with biological effects, accelerating the development of safer, animal-free testing methods.
This research not only deepens our understanding of nano material toxicity but also offers a powerful tool for safer nano material development, reducing reliance on animal testing. ToxAtlas could improve the way we assess and mitigate the risks of emerging nano materials in medicine, industry, and environmental safety.
International Collaboration & Publication
The study, "Toward a ToxAtlas of Carbon-Based Nano materials: Single-Cell RNA Sequencing Reveals Initiating Cell Circuits in Pulmonary Inflammation," was published in ACS Nano and involved researchers from Germany, Denmark, Switzerland, and the UK.
Original publication: https://pubmed.ncbi.nlm.nih.gov/41183169/
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.