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Injectable hydrogel with MSNs/microRNA-21-5p delivery enables both immunomodification and enhanced angiogenesis for myocardial infarction therapy in pigs
Science Advances ( IF 13.6 ) Pub Date : 2021-02-24 , DOI: 10.1126/sciadv.abd6740
Yan Li 1, 2 , Xin Chen 3 , Ronghua Jin 3 , Lu Chen 1 , Ming Dang 4 , Hao Cao 5 , Yun Dong 5 , Bolei Cai 2 , Guo Bai 1 , J Justin Gooding 6 , Shiyu Liu 7 , Duohong Zou 1 , Zhiyuan Zhang 1 , Chi Yang 1
Affiliation  

Current therapeutic strategies such as angiogenic therapy and anti-inflammatory therapy for treating myocardial infarction have limited success. An effective approach may benefit from resolution of excessive inflammation combined with enhancement of angiogenesis. Here, we developed a microRNA-21-5p delivery system using functionalized mesoporous silica nanoparticles (MSNs) with additional intrinsic therapeutic effects. These nanocarriers were encapsulated into an injectable hydrogel matrix (Gel@MSN/miR-21-5p) to enable controlled on-demand microRNA-21 delivery triggered by the local acidic microenvironment. In a porcine model of myocardial infarction, we demonstrated that the released MSN complexes notably inhibited the inflammatory response by inhibiting the polarization of M1 macrophage within the infarcted myocardium, while further microRNA-21-5p delivery by MSNs to endothelial cells markedly promoted local neovascularization and rescued at-risk cardiomyocytes. The synergy of anti-inflammatory and proangiogenic effects effectively reduced infarct size in a porcine model of myocardial infarction.



中文翻译:

具有 MSNs/microRNA-21-5p 递送的可注射水凝胶能够在猪心肌梗塞治疗中实现免疫修饰和增强血管生成

目前用于治疗心肌梗塞的治疗策略如血管生成疗法和抗炎疗法的成功有限。一种有效的方法可能受益于过度炎症的消退和血管生成的增强。在这里,我们使用功能化的介孔二氧化硅纳米粒子 (MSN) 开发了一种 microRNA-21-5p 递送系统,该系统具有额外的内在治疗效果。这些纳米载体被封装在可注射的水凝胶基质 (Gel@MSN/miR-21-5p) 中,以实现由局部酸性微环境触发的可控的按需 microRNA-21 递送。在猪心肌梗死模型中,我们证明释放的 MSN 复合物通过抑制梗死心肌内 M1 巨噬细胞的极化显着抑制炎症反应,而通过 MSN 进一步向内皮细胞递送 microRNA-21-5p 可显着促进局部新血管形成并挽救高危心肌细胞。抗炎和促血管生成作用的协同作用有效地减少了猪心肌梗塞模型中的梗塞面积。

更新日期:2021-02-25
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