School of Medicine, Anhui Provincial Engineering Laboratory of Occupational Health and Safety, Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Anhui University of Science and Technology, Key Laboratory of Industrial Dust Prevention and Control & Occupational Health and Safety, Ministry of Education, Huainan, China.
Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health & Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, University of Science and Technology of China, Hefei, China.
Environ Toxicol. 2023 Jul;38(7):1494-1508. doi: 10.1002/tox.23781. Epub 2023 Apr 5.
Silicosis is a life-threatening lung fibrotic disease caused by excessive inhalation of environmental exposure to crystalline silica-containing dust, whereas achieving therapeutic cures are constrained. Antioxidation and anti-inflammation are currently recognized as effective strategies to counteract organ fibrosis. Using naturally occurring phytomedicines quercetin (Qu) has emerged in antagonizing fibrotic disorders involving oxidative stress and inflammation, but unfortunately the hydrophilicity deficiency. Herein, chitosan-assisted encapsulation of Qu in nanoparticles (Qu/CS-NPs) was first fabricated for silicosis-associated fibrosis treatment by pulmonary delivery. Qu/CS-NPs with spherical diameters of ~160 nm, demonstrated a high Qu encapsulated capability, excellent hydrophilic stability, fantastic oxidation radical scavenging action, and outstanding controlled as well as slow release Qu action. A silicosis rat model induced by intratracheal instillation silica was established to estimate the anti-fibrosis effect of Qu/CS-NPs. After intratracheal administration, CS-NPs markedly enhanced Qu anti-fibrotic therapy efficacy, accompanying the evident changes in reducing ROS and MDA production to mitigate oxidative stress, inhibiting IL-1β and TNF-α release, improving lung histological architecture, down-regulating α-SAM levels and suppressing ECM deposition, and thereby ameliorating silica-induced pulmonary fibrosis. Results manifested that the augmented antioxidant and anti-inflammatory activities of Qu by CS-NPs delivery was a result of achieving this remarkable improvement in curative effects. Combined with negligible systemic toxicity, nano-decorated Qu may provide a feasible therapeutic option for silicosis therapy.
硅肺是一种危及生命的肺部纤维化疾病，由过量吸入含有结晶二氧化硅的环境粉尘引起，而目前的治疗方法受到限制。抗氧化和抗炎作用已被认为是对抗器官纤维化的有效策略。利用天然存在的植物药槲皮素（Qu）来对抗涉及氧化应激和炎症的纤维化疾病，但其亲水性不足。本文首次采用壳聚糖辅助包封槲皮素（Qu/CS-NPs），通过肺部给药治疗与硅肺相关的纤维化。Qu/CS-NPs 的粒径约为 160nm，具有高的 Qu 包封能力、优异的亲水性稳定性、出色的氧化自由基清除作用以及良好的控制和缓慢释放 Qu 的作用。通过气管内滴注二氧化硅建立硅肺大鼠模型，评估 Qu/CS-NPs 的抗纤维化作用。气管内给药后，CS-NPs 显著增强了 Qu 的抗纤维化治疗效果，伴随着明显降低 ROS 和 MDA 生成、减轻氧化应激、抑制 IL-1β和 TNF-α释放、改善肺组织学结构、下调α-SAM 水平和抑制 ECM 沉积的变化，从而改善二氧化硅引起的肺纤维化。结果表明，CS-NPs 递送增加了 Qu 的抗氧化和抗炎活性，从而显著提高了治疗效果。结合其轻微的全身毒性，纳米修饰的 Qu 可能为硅肺治疗提供一种可行的治疗选择。
