Perfluorocarbon Nanoemulsions Enhance Therapeutic siRNA Delivery in the Treatment of Pulmonary Fibrosis.
Perfluorocarbon Nanoemulsions Enhance Therapeutic siRNA Delivery in the Treatment of Pulmonary Fibrosis.
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全氟化合物纳米乳剂在治疗肺纤维化时增强了治疗性siRNA递送。
DOI：
10.1002/advs.202103676
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Oupický D
中科院分区：
文献类型：
--
作者：
Ding L;Tang S;Tang W;Mosley DD;Yu A;Sil D;Romanova S;Bailey KL;Knoell DL;Wyatt TA;Oupický D
治疗性siRNA的局部肺部施用代表了治疗肺纤维化的有希望的方法，其目前受到低效递送的阻碍。报道了全氟辛基溴（PFOB）纳米乳剂的开发，其作为提高基于聚阳离子的siRNA的肺部递送效率的方式。结果表明，聚阳离子/siRNA/PFOB纳米乳剂能够有效地沉默STAT 3的表达并抑制趋化因子受体CXCR 4-肺纤维化中的两个经验证的靶标。体外和体内结果均表明，纳米乳液改善粘液渗透并促进siRNA的有效细胞递送。博莱霉素诱导的肺纤维化小鼠的肺部治疗显示出对疾病进展的强烈抑制和动物存活的显著延长。总的来说，该研究指出了一种有前途的肺纤维化局部治疗策略。本文报道了能够安全有效地递送肺部siRNA的全氟化碳纳米乳剂，其具有肺深部渗透性和胞质siRNA递送，以介导肺纤维化中有效的肺STAT 3沉默和CXCR 4抑制。报道的发现可能导致通过非侵入性递送的肺纤维化的新治疗的发展。
Local pulmonary administration of therapeutic siRNA represents a promising approach to the treatment of lung fibrosis, which is currently hampered by inefficient delivery. Development of perfluorooctylbromide (PFOB) nanoemulsions as a way of improving the efficiency of pulmonary polycation‐based delivery of siRNA is reported. The results show that the polycation/siRNA/PFOB nanoemulsions are capable of efficiently silencing the expression of STAT3 and inhibiting chemokine receptor CXCR4—two validated targets in pulmonary fibrosis. Both in vitro and in vivo results demonstrate that the nanoemulsions improve mucus penetration and facilitate effective cellular delivery of siRNA. Pulmonary treatment of mice with bleomycin‐induced pulmonary fibrosis shows strong inhibition of the progression of the disease and significant prolongation of animal survival. Overall, the study points to a promising local treatment strategy of pulmonary fibrosis. This paper reports perfluorocarbon nanoemulsions capable of safe and effective pulmonary siRNA delivery with deep lung penetration and cytosolic siRNA delivery to mediate effective pulmonary STAT3 silencing and CXCR4 inhibition in pulmonary fibrosis. The reported finding may lead to a development of novel treatment of lung fibrosis via noninvasive delivery.
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影响因子：
5.8
作者：
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影响因子：
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作者：
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通讯作者：
Oupicky, David