BODIPY labeled Cellulose Nanocrystals (CNCs) Induces Il-1β secretion and Antioxidant Response in a Mitochondrial ROS-independent Manner

Abstract

Cellulose nanocrystals (CNCs) are rod-like nanomaterials that can be easily obtained via acidic hydrolysis of native cellulose. There has been a growing interest in modifying CNCs for biomedical purposes, including bioimaging. This emerging interest in CNCs lead us to synthesize a functionalized CNCs with a green-fluorescent BODIPY. Since needle-like molecules as well as fluorophores may induce reactive oxygen species (ROS), and these aspects are associated with NLRP3 inflammasome activation, the goal this study was to investigate whether CNCs-BIODIPY increases mitochondrial ROS leading to increases in the intracellular antioxidant defense and inflammatory response. Mouse macrophage-like cells (J774A.1) and PMA-stimulated human monocyte cells (THP-1) were treated with different concentrations of CNCs-BIODIPY, in presence or absence of LPS. After treatment, J774A.1 cells were harvested and intracellular levels of inflammatory proteins (NLRP3 and IL-1β) and the antioxidant enzymes (PrxSO3, Catalase and SOD1) were analyzed by western blotting in cell lysates. Mature IL-1β levels were analyzed by ELISA in cell supernatants and lysates from both cell lines and mitochondrial ROS by MitoSox in J774A.1 cells. The results indicated that levels of NLRP3 and pro-IL-1 β were increased in non LPS-stimulated cells as well as the antioxidant enzymes catalase and oxidized peroxiredoxins, PrxSO3. However, no significant changes in mitochondrial ROS production was found, in comparison to control conditions. Overall, our results revealed that CNCs-BIOPIDY increased antioxidant enzymes and NLRP3 inflammasome pathway suggesting that it may not be suitable to systemic biomedical applications in the tested concentrations.