Liu Shuai, Chen Daiqin, Li Xue, Guan Mirong, Zhou Yue, Li Lei, Jia Wang, Zhou Chen, Shu Chunying, Wang Chunru, Bai Chunli
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Nanoscale. 2020 Aug 28;12(33):17470-17479. doi: 10.1039/d0nr04401f.
Chronic exposure to crystalline silica causes the development of silicosis, which is one of the most important occupational diseases worldwide. In the early stage of silicosis, inhaled silica crystals initiate oxidative stress, a cycle of persistent inflammation and lung injury. And it is crucial to prevent the deteriorative progression in the onset of the disease. Herein, we present a promising candidate for the treatment of crystalline silica-induced pulmonary inflammation, using a silicosis mouse model caused by intratracheal instillation based on local administration of β-alanine and hydroxyl functionalized C70 fullerene nanoparticles (FNs). The results demonstrate that FNs could significantly alleviate inflammatory cells infiltration, lower the secretion of pro-inflammatory cytokines, and reduce the destruction of lung architecture stimulated by crystalline silica. Further investigations reveal that FNs could effectively inhibit the activation of NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome, and thus prevent the secretion of mature IL-1β and neutrophil influx, deriving from the superior ROS scavenging capability. Importantly, FNs could not cause any obvious toxicity after pulmonary administration.
长期接触结晶二氧化硅会导致矽肺病的发生，矽肺病是全球最重要的职业病之一。在矽肺病的早期阶段，吸入的二氧化硅晶体引发氧化应激，这是一个持续炎症和肺损伤的循环。并且在疾病发作时预防病情恶化至关重要。在此，我们基于局部给药β-丙氨酸和羟基官能化的C70富勒烯纳米颗粒（FNs），利用气管内滴注引起的矽肺病小鼠模型，提出了一种治疗结晶二氧化硅诱导的肺部炎症的有前景的候选方案。结果表明，FNs可显著减轻炎性细胞浸润，降低促炎细胞因子的分泌，并减少结晶二氧化硅刺激引起的肺结构破坏。进一步研究表明，FNs可有效抑制NLRP3（含NACHT、LRR和PYD结构域的蛋白3）炎性小体的激活，从而防止成熟IL-1β的分泌和中性粒细胞流入，这源于其卓越的活性氧清除能力。重要的是，FNs肺部给药后不会引起任何明显的毒性。
