Cancer nanomedicine primarily aim to direct drugs delivery to cancer cells but tumoraccumulation remains suboptimal (Mittelheisser et al. Adv. Mater., 2022). To circumvent thislimitation, activating immune cells with nanoparticles (NPs) is an emerging concept.However, upon engagement, whether NPs change the fate of immune cells that take themup remains unknown and one needs to throughly assess such impact to identify optimal NPs.Here, we characterized the response of immune cells to a selection of nanomaterialsclassically used in biomedical applications. Doing so, we aim at rationalizing the selection ofspecific NPs to undergo novel targeted approaches. Through bulk RNA-sequencing andproteomic analyses, we first investigated the impact of 6 NPs (lipidic, polymeric,organic/inorganic) on negatively isolated CD3 - CD56 + human NK cells and CD3 + human panT cells. Amongst all the NPs studied, we observed that the oxidated carbon nanotubestriggered wide transcriptome and proteome modifications in both pan-T and NK cells,whereas the other NPs exhibit mild to low impact into both NK and pan T-cells. Interestingly,we observed that only polymeric NPs induced a pre-activated state in NK cells with anoverexpression of the CCL5 chemokine and the cathepsin Z. Based on these results, weidentified one type of polymeric NPs as potential candidate for further NK cell targetingapproaches.

Disclosure Information V. Mittelheisser: None. X. Coubez: None. O. Lefebvre: None. J.G. Goetz: None. A. Detappe: None.