Zhong Jiayuan, Shi Lei, Liu Zhiwei, Ni Kai, Liu Lei, Pan Yan, Li Jingjing, Yu Xiaowei, Deng Linhong, Luo Mingzhi
Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, School of Medical and Health Engineering, Changzhou University, Changzhou, China.
Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, China.
Front Physiol. 2025 Jun 30;16:1566716. doi: 10.3389/fphys.2025.1566716. eCollection 2025.
FeO nanoparticles have been developed as carriers to transport drugs through airway mucus (AM); however, their impacts on the rheological properties of AM, especially in disease states, are unknown. In this study, we investigated the abilities of FeO nanoparticles dispersed in various media to alter the microstructure and rheological behaviors of simulated asthmatic AM. Here, the simulated AM was prepared via reconstituted mucins and other components in a composition resembling that of human AM reported in asthma, followed by treatment with FeO nanoparticles before and after curing. Subsequently, the AM samples treated with and without FeO nanoparticles were examined for their microstructures by optical immunofluorescence microscopy and for the rheological behaviors via steady-state and dynamic rotational rheometry. The results indicate that the FeO nanoparticles disrupt the mucus microstructure by inducing protein aggregation to increase the pore size and fiber diameter of the AM. However, the FeO nanoparticles significantly reduced the magnitudes of the viscoelastic properties of AM, including apparent viscosity, yield stress, and dynamic viscoelastic modulus. Although the addition of FeO nanoparticles before and after curing of AM appeared to produce similar effects, these effects had greater magnitudes when the nanoparticles were added before curing. The effects were also dependent on the concentration and surface property determined by the dispersion medium of the nanoparticles; accordingly, FeO nanoparticles dispersed at a concentration of 0.4 mg/mL in HO were the most potent at altering the microstructure and rheology of AM, producing better results than the concentration of 0.4 mg/mL of the conventional mucolytic chymotrypsin. Furthermore, tests on mucus samples collected from asthmatic patients showed similar results to those obtained with the simulated AM. Together, these findings suggest that FeO nanoparticles per se are useful as not only drug carriers but also expectorant agents for AM clearance therapy; they may also be more beneficial than pharmaceutical mucolytics owing to their wide availability and high biocompatibility.
FeO纳米颗粒已被开发为通过气道黏液（AM）运输药物的载体；然而，它们对AM流变学特性的影响，尤其是在疾病状态下的影响尚不清楚。在本研究中，我们研究了分散在各种介质中的FeO纳米颗粒改变模拟哮喘AM微观结构和流变行为的能力。在此，通过重组黏蛋白和其他成分制备模拟AM，其组成类似于哮喘中报道的人类AM，然后在固化前后用FeO纳米颗粒进行处理。随后，通过光学免疫荧光显微镜检查有无FeO纳米颗粒处理的AM样品的微观结构，并通过稳态和动态旋转流变仪检查其流变行为。结果表明，FeO纳米颗粒通过诱导蛋白质聚集破坏黏液微观结构，以增加AM的孔径和纤维直径。然而，FeO纳米颗粒显著降低了AM的黏弹性特性的大小，包括表观黏度、屈服应力和动态黏弹性模量。尽管在AM固化前后添加FeO纳米颗粒似乎产生了相似的效果，但在固化前添加纳米颗粒时这些效果的程度更大。这些效果还取决于由纳米颗粒分散介质决定的浓度和表面性质；因此，以0.4 mg/mL浓度分散在HO中的FeO纳米颗粒在改变AM的微观结构和流变学方面最有效，比传统黏液溶解酶胰凝乳蛋白酶0.4 mg/mL的浓度产生更好的结果。此外，对哮喘患者收集的黏液样本的测试显示出与模拟AM获得的结果相似。总之，这些发现表明FeO纳米颗粒本身不仅可用作药物载体，还可用作AM清除治疗的祛痰剂；由于其广泛的可用性和高生物相容性，它们可能也比药物黏液溶解剂更有益。
