The Uptake of Metallic Nanoparticles in Breast Cancer Cell Lines is Modulated by the Hyaluronan-CD44 Axis
Radiation enhancement is a promising anticancer approach based on a local radiation dose increase due to the presence of metallic nanoparticles (NPs) within cancer cells. Depending on their composition, size, and cellular properties, NPs can follow multiple cellular pathways and entry routes. We observed that gold, platinum, and TiO<sub>2</sub> NPs are internalized at higher levels in mesenchymal cells compared to epithelial cells in breast cancer models. A global survey of gene expression between epithelial and mesenchymal cells exposed to 4 different NP types revealed an involvement of membrane structure, and further experiments confirmed that hyaluronic acid (HA) and its receptor CD44 are mediators of metallic NP uptake into cells. We extended our results to a larger panel of breast cancer cell lines and again showed a preferential uptake of all NPs tested in mesenchymal cells and relied on the HA/CD44 axis. These data provide considerations for the design of NP-based therapies targeting mesenchymal cancer cells, which are often resistant to treatment and correlate with poor prognosis and tumor recurrence.
Authors
- Sylvie Chevillard (ORCID: https://orcid.org/0000-0001-5889-4041)
- Céline Lacrouts
- Núria Fonknechten
- Johanna Noireaux (ORCID: https://orcid.org/0000-0002-1161-9277)
- Anna Campalans (ORCID: https://orcid.org/0000-0001-7089-6891)
- Cécile Mathé
- Guillaume Piton (ORCID: https://orcid.org/0000-0002-0124-0909)
- Emmanuelle Bourneuf (ORCID: https://orcid.org/0000-0003-4305-3180)
- Marie Hullo (ORCID: https://orcid.org/0000-0002-0367-1462)
Institutions
- Environment and Climate Change Canada (CA)
- Inserm (FR)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Committee on Climate Change (GB)
- Laboratoire National de Métrologie et d'Essais (FR)
- Institut des Cellules Souches pour le Traitement et l'Étude des Maladies Monogéniques (FR)
- Institut de Radiobiologie Cellulaire et Moléculaire (FR)
Publication Details
- Journal
- ACS Nano
- Published
- 2025-08-04
- DOI
- https://doi.org/10.1021/acsnano.5c02886
- Citations
- 3
- Primary Topic
- Radiation Therapy and Dosimetry
- Type
- article
- Field-Weighted Citation Impact
- 4.56
Funders
- Ministère de l'Education Nationale, de l'Enseignement Superieur et de la Recherche
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives
- Université Paris-Saclay