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.