Nanomaterials Trigger Functional Anti‐Tumoral Responses in Primary Human Immune Cells
Targeting the immune system with nanoparticles (NPs) to deliver immunomodulatory molecules emerged as a solution to address intra-tumoral immunosuppression and enhance therapeutic response. While the potential of nanoimmunotherapies in reactivating immune cells has been evaluated in several preclinical studies, the impact of drug-free nanomaterials on the immune system remains unknown. Here, the molecular and functional response of human NK cells and pan T cells to a selection of five NPs that are commonly used in biomedical applications are characterized. After a pre-screen to evaluate the toxicity of these nanomaterials on immune cells, ultrasmall silica-based gadolinium (Si-Gd) NPs and poly(lactic-co-glycolic acid) (PLGA) NPs are selected for further investigation. Bulk RNA-sequencing and flow cytometry analysis showcase that PLGA NPs trigger a transcriptional priming toward activation in NK and pan T cells. While PLGA NPs improved NK cells anti-tumoral functions in a cytokines-deprived environment, Si-Gd NPs significantly impaired T cells activation as well as functional responses to a polyclonal antigenic stimulation. Altogether, PLGA NPs are identified as an attractive strategy for reactivating the immune system of cancer patients.
Authors
- Annabel Larnicol (ORCID: https://orcid.org/0000-0002-2312-9961)
- Juliette Blumberger
- Jacky G. Goetz (ORCID: https://orcid.org/0000-0003-2842-8116)
- Vincent Mittelheisser (ORCID: https://orcid.org/0000-0002-0456-3957)
- Marie‐Charlotte Diringer
- Tristan Stemmelen (ORCID: https://orcid.org/0000-0002-4382-1277)
- Mainak Banerjee (ORCID: https://orcid.org/0000-0001-9983-8222)
- Amandine Dupas (ORCID: https://orcid.org/0009-0001-0846-6011)
- Sébastien Harlepp (ORCID: https://orcid.org/0000-0001-8891-7953)
- Olivier Lefèbvre (ORCID: https://orcid.org/0000-0001-9130-9174)
- François Lux (ORCID: https://orcid.org/0000-0003-1568-0240)
- Angélique Pichot
- Shayamita Ghosh (ORCID: https://orcid.org/0000-0002-4315-4443)
- Chloé Moritz
- Raphaël Carapito (ORCID: https://orcid.org/0000-0002-7036-442X)
- Anne Molitor (ORCID: https://orcid.org/0000-0003-1646-2325)
- Loı̈c J. Charbonnière (ORCID: https://orcid.org/0000-0003-0328-9842)
- Christine Carapito (ORCID: https://orcid.org/0000-0002-0079-319X)
- Alexandre Detappe (ORCID: https://orcid.org/0000-0001-9364-1621)
- Louis Bochler (ORCID: https://orcid.org/0009-0003-7050-3287)
- Olivier Tillement (ORCID: https://orcid.org/0000-0001-7166-6537)
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Universitaire de France (FR)
- Institut National des Sciences Appliquées de Strasbourg (FR)
- Institut Pluridisciplinaire Hubert Curien (FR)
- Institut de Cancérologie Strasbourg (FR)
- La Ligue Contre le Cancer (FR)
- Biomechanics Institute of Valencia (ES)
- Institut Lumière Matière (FR)
- Hôpitaux Universitaires de Strasbourg (FR)
- Institut Polytechnique de Bordeaux (FR)
- Hôpital Civil, Strasbourg (FR)
- Université de Strasbourg (FR)
Publication Details
- Journal
- Advanced Science
- Published
- 2025-07-12
- DOI
- https://doi.org/10.1002/advs.202505729
- Citations
- 1
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation
- Infrastructures en Biologie Santé et Agronomie
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Université de Strasbourg
- Fondation ARC pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- HORIZON EUROPE European Research Council