Investigating the effect of physicochemical properties of nanomaterials on the NLRP3 inflammasome

With the growing use of nanomaterials for diagnostic and therapeutic purposes, it has become essential to understand their interaction with the immune system, specifically the innate immune system. The innate immune system acts as the first level of defense against any injury or foreign material. A key component of the innate immune system, the NLRP3 inflammasome, is known to be responsible for various inflammatory disorders in the body. Recent studies have shown that apart from common stimuli like pathogens, extracellular ATP, and RNA-DNA hybrids, nanoparticles are also capable of effecting NLRP3 activation and subsequent inflammation, via nanoparticle-associated molecular patterns (NAMPs). Understanding these NAMPs and the physicochemical properties that affect them, is crucial in the design of more effective materials. To facilitate this understanding, I synthesized and characterized three different nanomaterials with different properties such as hydrophobicity and surface charge, shape, and composition. The effect of these nanoparticles on the NLRP3 inflammasome was evaluated in macrophages via enzyme-linked immunosorbent assay (ELISA). The cell viability and internalization of these particles were also investigated. To visualize the effect on the NLRP3 inflammasome ASC Speck analysis was done. Finally, to gain some mechanistic insight, I performed lysosomal rupture, calcium influx and mitochondrial reactive oxygen species (ROS) studies. Through this work, I hope to shed light on some of the physicochemical properties that need to be considered when designing new materials.