Cell therapy is an important new method in medicine and is being used for the treatment of an increasing number of diseases. The challenge here is the precise tracking of cells in the body and their visualization. One method to visualize cells more easily with current methods is their labeling with nanoparticles before injection. However, for a safe and sufficient cell labeling, the nanoparticles need to remain in the cell and not be exocytosed. Here, we test a glucose-PEG-coated gold nanoparticle for the use of such a cell labeling. To this end, we investigated the nanoparticle exocytosis behavior from PLX-PAD cells, a cell type currently in clinical trials as a potential therapeutic agent. We showed that the amount of exocytosed gold from the cells was influenced by the uptake time and loading amount. This observation will facilitate the safe labeling of cells with nanoparticles in the future and contribute to stem cell therapy research.

The concept of safe-by-design (SbD) can help toxicologists and risk assessors to keep pace with the rapidly expanding field of nanotechnology. As part of SbD, the hazard potential of a new nanomaterial (NM) is identified at the first stages of product development. For this, simple yet predictive toxicity assays are crucial. We investigated the suitability of several in vitro models and exposure methods to predict the human (pulmonary) inflammation potential of NMs. Four silica NMs were selected of which in vivo pulmonary toxicity ranking had previously been established: DQ12 (quartz) > NM-203 (fumed silica) > Colloidal silica > Silanized colloidal silica. Several cell types including a 3D human airway epithelial model, lung epithelial cell lines, and immune cell lines, either in mono- or co-culture were exposed to the four materials either in a submerged setting or at the air-liquid interface (ALI). After 24 hours of exposure, cytokine response was assessed using either 13-plex LegendPlex, ELISA, or qPCR, and toxicity rankings were compared. The results indicate differences in sensitivity between cell models and exposure methods. Submerged exposure of a cell-line seems a suitable first tier for SbD hazard testing in case of NMs that can easily be dispersed. For NMs that are not compatible with submerged testing, ALI exposure might be needed. Higher tier testing might be used to confirm the ranking.