title: Direct monitoring of pulmonary disease treatment biomarkers using plasmonic gold nanorods with diffusion-sensitive OCT.
abstract: The solid concentration of pulmonary mucus (wt%) is critical to respiratory health. In patients with respiratory disease, such as Cystic Fibrosis (CF) and Chronic Obstructive Pulmonary Disorder (COPD), mucus hydration is impaired, resulting in high wt%. Mucus with high wt% is a hallmark of pulmonary disease that leads to obstructed airways, inflammation, and infection. Methods to measure mucus hydration in situ and in real-time are needed for drug development and personalized therapy. We employed plasmonic gold nanorod (GNR) biosensors that intermittently collide with macromolecules comprising the mucus mesh as they self-diffuse, such that GNR translational diffusion (DT) is sensitive to wt%. GNRs are attractive candidates for bioprobes due to their anisotropic optical scattering that makes them easily distinguishable from native tissue using polarization-sensitive OCT. Using principles of heterodyne dynamic light scattering, we developed diffusion-sensitive optical coherence tomography (DS-OCT) to spatially-resolve changing DTin real-time. DS-OCT enables, for the first time, direct monitoring of changes in nanoparticle diffusion rates that are sensitive to nanoporosity with spatial and temporal resolutions of 4.7 μm and 0.2 s. DS-OCT therefore enables us to measure spatially-resolved changes in mucus wt% over time. In this study, we demonstrate the applicability of DS-OCT on well-differentiated primary human bronchial epithelial cells during a clinical mucus-hydrating therapy, hypertonic saline treatment (HST), to reveal, for the first time, mucus mixing, cellular secretions, and mucus hydration on the micrometer scale that translate to long-term therapeutic effects.
authors.affiliation: Department of Physics and Astronomy, University of North Carolina at Chapel Hill, NC 27599-3255, USA. aold@physics.unc.edu.
authors.forename: R L
authors.initials: RL
authors.lastname: Blackmon
authors.forename: S M
authors.initials: SM
authors.lastname: Kreda
authors.forename: P R
authors.initials: PR
authors.lastname: Sears
authors.forename: B S
authors.initials: BS
authors.lastname: Chapman
authors.forename: D B
authors.initials: DB
authors.lastname: Hill
authors.forename: J B
authors.initials: JB
authors.lastname: Tracy
authors.forename: L E
authors.initials: LE
authors.lastname: Ostrowski
authors.forename: A L
authors.initials: AL
authors.lastname: Oldenburg
mesh_terms: D015374:Biosensing Techniques; D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D004058:Diffusion; D004847:Epithelial Cells / Q000166:cytology*; D006046:Gold; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy; D009093:Mucus / Q000737:chemistry*; D043942:Nanotubes; D041623:Tomography, Optical Coherence
chemical_list: D006046:Gold