LAUSR

Nanodiamonds (ND), especially fluorescent nanodiamonds represent potentially applicable drugs and probes carriers for in vitro/in vivo applications. The main purpose of this study was to relate physical-chemical properties of carboxylated ND to their intracellular distribution, impact on membranes and cell immunity - activation of inflammasome in in vitro THP-1 cell line model. Dynamic light scattering, nanoparticle tracking analysis and microscopic methods were used to characterize nanodiamond particles and their intracellular distribution. Fluorescent NDs penetrated cell membranes by both macropinocytosis and mechanical cutting through cell membranes. We proved accumulation of fluorescent NDs in lysosomes. In this case, lysosomes were destabilised and Cathepsin B was released into cytoplasm and triggered pathways leading to activation of inflammasome NLRP3 as detected in THP-1 cells. Activation of inflammasomes by ND represents an important event that could underlie the described toxicological effects in vivo induced by NDs. According to our knowledge this is the first in vitro study demonstrating direct activation of inflammasome by ND. These findings are important for understanding the mechanism(s) of action of ND complexes and explain the ambiguity of the existing toxicological data.