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Development of a method for in situ nanorheology of human airway mucus

开发人类气道粘液原位纳米流变学方法

基本信息

批准号：
8519527
负责人：
Amy L Oldenburg
金额：
$ 16.81万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8519527
关键词：
Address Air Animal Model Anisotropy Binding Biological Models Bronchi Cell Culture Techniques Chronic Obstructive Airway Disease Clinical assessments Collection Complex Cystic Fibrosis Data Detection Development Diagnosis Diffusion Disease Progression Dose Drug Delivery Systems Epithelial Flow-It Frequencies Future Gold Harvest Heterogeneity Human Hydration status Image Imaging technology In Situ In Vitro Knowledge Lead Learning Length Light Link Liquid substance Lung diseases Maps Measurement Measures Mechanics Methods Modeling Molecular Weight Monitor Motion Mucociliary Clearance Mucous body substance Mus Normal Range Optical Coherence Tomography Optics Physiological Polyethylene Glycols Property Resolution Retinal Cone Rheology Saline Signal Transduction Simulate Solid Speed Statistical Study Structure of ciliary processes System Techniques Technology Therapeutic Intervention Thick Time Translations Treatment Efficacy Validation Work base in vitro Model in vivo light scattering nanolitre nanorod nephelometry new technology novel plasmonics polarized light prevent response therapy development vector viscoelasticity

项目摘要

DESCRIPTION (provided by applicant): We propose to develop a novel nanorheology platform to simultaneously map mucus viscoelasticity and mucus flow in situ. Increase in airway mucus complex viscoelastic shear modulus (G*) hinders mucus clearance and is associated with respiratory diseases including chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). In the short term, this new platform will provide a more complete biophysical picture of mucociliary clearance and enable better models, leading to new treatment paradigms. In the long term, this platform may be translatable to in vivo mucus monitoring for assessment of disease progression and therapeutic interventions. Our nanorheology platform is based upon dynamic light scattering (DLS) from plasmonic gold nanorods (GNRs) monitored using optical coherence tomography (OCT). Specifically, the cross-polarized light scattering signal from GNRs provides information about their rotational diffusion rate, which is related through a generalized Stokes-Einstein relationship to the G* of the mucus. GNRs are advantageous as rheological probes because their high anisotropy and plasmon-resonance provides a unique optical signal against endogenous mucus light scatterers, and their small size provides a fast rotational DLS signal which allows for more rapid collection of rheological data. Importantly, OCT provides depth-resolved DLS measurements of GNR diffusion, which will enable spatial mapping of heterogeneities in mucus G*, particularly as a function of distance from the periciliary layer. By linking these measurements with OCT- based tracking of mucus flow, it will provide a more complete biophysical picture of mucociliary clearance. Our first aim is to validate the DLS-OCT nanorheology technique in controlled complex fluids against standard bead microrheology and bulk rheology. Subsequently, we will validate this technique using non- muco-adherent GNRs in mucus harvested from human bronchi-epithelial (hBE) cultures, and evaluate the response as a function of % solids. Our second aim is to employ DLS-OCT to monitor flowing mucus in normal and CF-like hBE model systems, using GNRs delivered by nebulization. We will associate measurements of G* with flow rate measured by speckle-tracking in OCT as a function of distance from the periciliary layer. In addition, we will determin the ability for OCT to monitor ciliary function during simulated hypertonic saline therapy and induced collapse and revival of ciliary activity in these models. By the completion of this study we will have validated DLS-OCT nanorheology against micro- and bulk rheology techniques, and established the sensitivity for mapping G* and quantifying % solids in a flowing mucus system, which will poise the technology for future in vivo studies in murine models of cystic fibrosis.

描述（由申请人提供）：我们建议开发一种新颖的纳米流变学平台，以同时绘制原位粘液粘弹性和粘液流动图。气道粘液复合体粘弹性剪切模量 (G*) 的增加会阻碍粘液清除，并与慢性阻塞性肺病 (COPD) 和囊性纤维化 (CF) 等呼吸系统疾病相关。在短期内，这个新平台将提供更完整的粘膜纤毛清除的生物物理图像，并实现更好的模型，从而带来新的治疗范例。从长远来看，该平台可以转化为体内粘液监测，以评估疾病进展和治疗干预。我们的纳米流变学平台基于使用光学相干断层扫描 (OCT) 监测的等离子体金纳米棒 (GNR) 的动态光散射 (DLS)。具体来说，来自 GNR 的交叉偏振光散射信号提供了有关其旋转扩散速率的信息，该信息通过广义斯托克斯-爱因斯坦关系与粘液的 G* 相关。 GNR 作为流变探针具有优势，因为它们的高各向异性和等离子体共振提供了针对内源性粘液光散射体的独特光学信号，并且它们的小尺寸提供了快速旋转 DLS 信号，从而可以更快速地收集流变数据。重要的是，OCT 提供了 GNR 扩散的深度分辨 DLS 测量，这将能够对粘液 G* 中的异质性进行空间映射，特别是作为距纤毛周围层距离的函数。通过将这些测量结果与基于 OCT 的粘液流动追踪联系起来，它将提供更完整的粘液纤毛清除的生物物理图像。我们的首要目标是根据标准珠微流变学和本体流变学来验证受控复杂流体中的 DLS-OCT 纳米流变学技术。随后，我们将使用从人支气管上皮 (hBE) 培养物中收获的粘液中的非粘膜粘附 GNR 来验证该技术，并评估作为固体百分比函数的响应。我们的第二个目标是采用 DLS-OCT 来监测正常和类 CF hBE 模型系统中的流动粘液，使用雾化提供的 GNR。我们将 G* 的测量值与 OCT 中散斑跟踪测量的流速关联起来，作为距纤毛周围层距离的函数。此外，我们将确定 OCT 在模拟高渗盐水治疗期间监测纤毛功能以及在这些模型中诱导纤毛活动崩溃和恢复的能力。这项研究完成后，我们将针对微观和本体流变学技术验证 DLS-OCT 纳米流变学，并建立绘制 G* 图谱和量化流动粘液系统中固体百分比的灵敏度，这将为未来囊性纤维化小鼠模型的体内研究奠定基础。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Spatial temperature mapping within polymer nanocomposites undergoing ultrafast photothermal heating via gold nanorods.

通过金纳米棒进行超快光热加热的聚合物纳米复合材料内的空间温度图。

DOI：
10.1039/c4nr05179c
发表时间：
2014
期刊：
Nanoscale
影响因子：
6.7
作者：
Maity,Somsubhra;Wu,Wei-Chen;Xu,Chao;Tracy,JosephB;Gundogdu,Kenan;Bochinski,JasonR;Clarke,LauraI
通讯作者：
Clarke,LauraI

Swept-Source Anatomic Optical Coherence Elastography of Porcine Trachea.

猪气管的扫描源解剖光学相干弹性成像。

DOI：
10.1117/12.2213186
发表时间：
2016
期刊：
Proceedings of SPIE--the International Society for Optical Engineering
影响因子：
0
作者：
Bu,Ruofei;Price,Hillel;Mitran,Sorin;Zdanski,Carlton;Oldenburg,AmyL
通讯作者：
Oldenburg,AmyL

Large-Scale Silica Overcoating of Gold Nanorods with Tunable Shell Thicknesses.

DOI：
10.1021/cm504764v
发表时间：
2015-04-28
期刊：
CHEMISTRY OF MATERIALS
影响因子：
8.6
作者：
Wu, Wei-Chen;Tracy, Joseph B.
通讯作者：
Tracy, Joseph B.

Multi-modal anatomical Optical Coherence Tomography and CT for in vivo Dynamic Upper Airway Imaging.

用于体内动态上呼吸道成像的多模式解剖光学相干断层扫描和 CT。

DOI：
10.1117/12.2250348
发表时间：
2017
期刊：
Proceedings of SPIE--the International Society for Optical Engineering
影响因子：
0
作者：
Balakrishnan,Santosh;Bu,Ruofei;Price,Hillel;Zdanski,Carlton;Oldenburg,AmyL
通讯作者：
Oldenburg,AmyL

Large-Scale Synthesis of Gold Nanorods through Continuous Secondary Growth.

DOI：
10.1021/cm402277y
发表时间：
2013-11-26
期刊：
CHEMISTRY OF MATERIALS
影响因子：
8.6
作者：
Kozek, Krystian A.;Kozek, Klaudia M.;Wu, Wei-Chen;Mishra, Sumeet R.;Tracy, Joseph B.
通讯作者：
Tracy, Joseph B.