Polysaccharide Nanofiber-Stabilized Pickering Emulsion Microparticles Induce Pyroptotic Cell Death in Hepatocytes and Kupffer Cells

Abstract

The intracellular uptake and interaction behavior of emulsion microparticles in liver cells critical to host defense and inflammation is significant to understanding their potential cytotoxicity and biomedical applications. In this study, the cell death responses of fibroblastic, hepatocyte, and Kupffer cells (KCs) induced by four types of emulsion particles that are stabilized by polysaccharide nanofibers (cellulose or chitin), an inorganic nanoparticle (β-tricalcium phosphate), or surfactants are compared. Pickering emulsion (PE) microparticles stabilized by polysaccharide nanofibers or inorganic nanoparticles have a droplet size of 1–3 µm, while the surfactant-stabilized emulsion has a diameter of ≈190 nm. Polysaccharide nanofiber-stabilized PEs (PPEs) markedly induce lactate dehydrogenase release in all cell types. Additionally, characteristic pyroptotic cell death, which is accompanied by cell swelling, membrane blebbing, and caspase-1 activation, occurs in hepatocytes and KCs. These PE microparticles are co-cultured with lipopolysaccharide-primed KCs associated with cytokine interleukin-1β release, and the PPEs demonstrate biological activity as a mediator of the inflammation response. Well-designed PPE microparticles induce pyroptosis of liver cells, which may provide new insight into regulating inflammation-related diseases for designing potent anticancer drugs and vaccine adjuvants.