title: Functionalized positive nanoparticles reduce mucin swelling and dispersion.
abstract: Multi-functionalized nanoparticles (NPs) have been extensively investigated for their potential in household and commercial products, and biomedical applications. Previous reports have confirmed the cellular nanotoxicity and adverse inflammatory effects on pulmonary systems induced by NPs. However, possible health hazards resulting from mucus rheological disturbances induced by NPs are underexplored. 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 and its operational mechanisms have not been resolved. Herein, we report 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 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 (Ca(2+) 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. This report also highlights the unexpected health risk of NP-induced change in mucus rheological properties resulting in possible mucociliary transport impairment on epithelial mucosa and related health problems. In addition, our data can serve as a prospective guideline for designing nanocarriers for airway drug delivery applications.
authors.affiliation: Bioengineering, University of California Merced, Merced, California, United States of America.
authors.forename: Eric Y T
authors.initials: EY
authors.lastname: Chen
authors.forename: Yung-Chen
authors.initials: YC
authors.lastname: Wang
authors.forename: Chi-Shuo
authors.initials: CS
authors.lastname: Chen
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chin
mesh_terms: D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D055598:Chemical Phenomena; D004533:Egtazic Acid / Q000494:pharmacology; D005089:Exocytosis; D006801:Humans; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D009077:Mucins / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D009077:Mucins; D014867:Water; D004533:Egtazic Acid