Localized delivery of miRNAs targets cyclooxygenases and reduces flexor tendon adhesions
Localized delivery of miRNAs targets cyclooxygenases and reduces flexor tendon adhesions
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miRNA 的局部递送靶向环氧合酶并减少屈肌腱粘连
DOI：
10.1016/j.actbio.2018.01.047
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发表时间：
2018
影响因子：
9.7
通讯作者：
Tang Jin Bo
中科院分区：
文献类型：
--
作者：
Zhou You Lang;Yang Qian Qian;Yan Ying Ying;Zhu Changlai;Zhang Luzhong;Tang Jin Bo
损伤肌腱愈合过程中粘连的形成仍然是临床实践中的一个难题。局部抗炎基因递送提供高的局部基因浓度，减少损伤肌腱微环境的炎症反应，并减少全身副作用以增强体内功效。在本研究中，我们设计了一种新型的局部持续基因递送系统，通过使用环氧合酶（考克斯-1和考克斯-2）工程化的miRNA质粒/纳米颗粒包埋在透明质酸（HA）水凝胶中来减少屈肌腱粘连。局部持续基因递送系统显著下调肌腱组织和周围皮下组织中考克斯-1和考克斯-2的表达。更重要的是，这种质粒/纳米颗粒水凝胶系统显著减少了组织粘连形成。这种方法提供了一种有效的治疗策略，以减少肌腱粘连，通过直接针对下调考克斯-1和考克斯-2表达的损伤tendon.Statement of SignificanceA本地持续基因递送系统的开发，以调节在特定的时间和特定的位置的肌腱粘连治疗的目标基因的表达。合成包埋在透明质酸水凝胶中的工程化miRNA质粒/纳米颗粒，以在具有炎症反应的肌腱愈合早期下调肌腱组织中环氧合酶的表达。这种质粒/纳米颗粒水凝胶系统提供了一种有效的治疗策略，通过直接下调受损肌腱微环境中考克斯-1和考克斯-2的表达来减弱肌腱粘连的形成。
The formation of adhesions during healing of an injured tendon remains a difficult problem in clinical practice. Local anti-inflammation gene delivery provides high local gene concentration, reduces the inflammatory response of the injured tendon microenvironment, and decreases systemic side effects to enhancein vivoefficacy. In this study, we designed a novel local sustained gene delivery system by using cyclooxygenase (COX-1 and COX-2)-engineered miRNA plasmid/nanoparticles embedded in hyaluronic acid (HA) hydrogel to reduce flexor tendon adhesions. The local sustained gene delivery system significantly downregulates COX-1 and COX-2 expression in the tendon tissue and the surrounding subcutaneous tissue. More importantly, this plasmid/nanoparticle hydrogel system significantly reduced tissue adhesion formation. This approach offers an effective therapeutic strategy to reduce tendon adhesions by directly targeting the down-regulation of COX-1 and COX-2 expression within the microenvironment of the injured tendon.Statement of SignificanceA local sustained gene delivery system was developed to regulate the expression of targeted genes in the specific time and location for tendon adhesion treatment. The engineered miRNA plasmid/nanoparticles embedded in hyaluronic acid hydrogel were synthesized to downregulate the expression of cyclooxygenases in the tendon tissue during the early stage of tendon healing with inflammatory response. This plasmid/nanoparticle hydrogel system offers an effective therapeutic strategy to attenuate the formation of tendon adhesion through direct downregulation of COX-1 and COX-2 expression within the microenvironment of the injured tendon.