Differential bioreactivity of neutral, cationic and anionic polystyrene nanoparticles with cells from the human alveolar compartment: robust response of alveolar type 1 epithelial cells

摘要: Engineered nanoparticles (NP) are being developed for inhaled drug delivery. This route is non-invasive and the major target; alveolar epithelium provides a large surface area administration absorption, without first pass metabolism. Understanding interaction between NPs target cells crucial safe effective NP-based We explored differential effect of neutral, cationic anionic polystyrene latex on human alveolus, using primary macrophages (MAC) type 2 (AT2) epithelial unique I-like cell (TT1). hypothesized that bioreactivity would relate to their chemistry, charge size as well functional role interacting in vivo. Amine- (ANP) carboxyl- modified (CNP) unmodified (UNP) NPs, 50 100 nm diameter, were studied. Cells exposed 1–100 μg/ml (1.25-125 μg/cm2; 0 μg/ml control) NP 4 24 h at 37 °C with or antioxidant, N-acetyl cysteine (NAC). assessed viability, reactive oxygen species (ROS), oxidised glutathione (GSSG/GSH ratio), mitochondrial integrity, morphology particle uptake (using electron microscopy laser scanning confocal microscopy). ANP-induced death occurred all types, inducing increased oxidative stress, disruption release cytochrome C, indicating apoptotic death. UNP CNP exhibited little cytotoxicity damage, although they induced ROS AT2 MACs. Addition NAC reduced ROS, but not MAC up 4 h. TT1 internalised formats, whereas only small fraction internalized ANP (not CNP). most resistant effects CNP. marked damage via apoptosis while low stress. models show strong particle-internalization compared model, reflecting function The 50 nm higher cells, stronger phagocytic cells.