The immunological barrier is among the most significant barriers in vivo. Macrophages and dendritic cells play a crucial role in immune responses, involving phagocytosis, antigen presentation, and triggering adaptive responses. Nanoscale drug-delivery vehicles, such as polymer-encapsulated lipid-bilayer nanodiscs, are of particular interest in the development of new therapeutic approaches, but require well-characterized human in vitro cell models. To this end, the present study differentiated human monocytes into two distinct states, resting macrophages and immature dendritic-like cells (iDCs). These cells served as model systems to assess the efficacy of lipid-bilayer nanodiscs encapsulated by anionic glyco-DIBMA (diisobutylene–maleic acid) or electroneutral sulfo-DIBMA polymers. Nanodisc–cell interaction studies—including cell viability, reactive oxygen species production, cytokine release, particle uptake, and activation marker expression—demonstrated that immune responses depend sensitively on the cell type and polymer and thus on the surface charge of the nanodiscs. Sulfo-DIBMA nanodiscs induced minimal immune cell activation, accompanied by cytokine release and reduced uptake of the nanodiscs by immune cells. In contrast, glyco-DIBMA nanodiscs exhibited increased interactions with cells, elicited pro-inflammatory immune responses, and promoted iDC maturation. This involved co-stimulatory and antigen-presenting molecules, potentially leading to T-cell activation. These findings underscore the potential of glyco-DIBMA nanodiscs to modulate immune responses through receptor-specific interactions, paving the way for immunotherapeutic strategies.

Concentrations of microplastic particles (MPs) in the environment are low, and cellular uptake is difficult to measure. Cancer tissue accumulates more MPs than normal tissue. This study aims to determine whether cellular stiffness measurements by atomic force microscopy could indicate whether cells ingested MPs. In this study, spheroids with different compositions were exposed to MPs, and Young’s moduli were compared to fluorescent readings of MP uptake in monolayer cultures. The tested cancer cell lines differed in their basal Young’s modulus and in the increases observed upon MP exposure, both in monolayer and spheroid culture. Young’s moduli of the THP-1-containing spheroids were higher than those of spheroids without macrophages and were higher after MP exposure than before. In monolayer culture, softer cells showed larger increases in Young’s modulus after MP exposure than did stiffer cells. The Young’s moduli of the cell monolayers under static and dynamic conditions were positively correlated. Young’s modulus could serve as a parameter for MP uptake and can differentiate MP-containing spheroids from non-exposed spheroids. In monolayer culture, Young’s modulus can identify cell lines that ingested MPs. However, complicated use and low throughput limit the broad application of atomic force microscopy in biological evaluation.