(274b) Functionalized Positive Nanoparticles Reduce Mucin Swelling and Dispersion

Multi-functionalized nanoparticles (NPs) have recently been extensively explored for their potential in novel drug delivery, nanomedicine applications and even in our daily life. Many previous reports have clearly demonstrated cellular nanotoxicity effects induced by airborne NPs. Accumulation of viscous poorly dispersed, and less transportable mucus leading to improper mucus rheology and dysfunctional mucociliary clearance are typically found to associate with many respiratory diseases such as asthma, cystic fibrosis (CF), and COPD (Chronic Obstructive Pulmonary Disease). Whether functionalized NPs can alter mucus rheology (viscosity) and its operational mechanisms have not been resolved. We report for the first time, that positively-charged functionalized NPs can hinder mucin gel hydration and effectively induce mucin aggregation. The positively-charged NPs can significantly reduce the rate of mucin matrix hydration/swelling by a maximum of 7.5 folds. These NPs significantly increase the size of aggregated mucin by approximately 30 times within 24 hrs. EGTA chelation of indigenous mucin crosslinkers (Ca2+ ions) was unable to effectively disperse NP-induced aggregated mucins. Our results have demonstrated that positively-charged functionalized NPs can impede mucin gel swelling by crosslinking the matrix resulting in potential dysfunctional mucociliary clearance and health problems. This report also highlights the unexpected health risk of NP-induced change in mucus rheology and possible mucociliary transport impairment on epithelial mucosa. In addition, our data can serve as a prospective guideline for airborne nanoparticle pollution limits. (Supported by NIH 1R15HL095039-01A1 and CITRIS #31 seed grant)