Peng Huiyu, Du Fangzhou, Wang Jingwen, Wu Yue, Wei Qian, Chen Aoying, Duan Yuhan, Shi Shuaiguang, Zhang Jingzhong, Yu Shuang
School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China.
Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
Pharmaceutics. 2024 Aug 23;16(9):1113. doi: 10.3390/pharmaceutics16091113.
miRNAs have been shown to be involved in the regulation of a variety of physiological and pathological processes, but their use in the treatment of diseases is still limited due to their instability. Biomimetic nanomaterials combine nanomaterials with cellular components that are readily modifiable and biocompatible, making them an emerging miRNA delivery vehicle. In this study, adipose-derived MSC membranes were wrapped around PLGA-PEI loaded with miR-21 through co-extrusion and later transplanted into C57BL/6 mice wounds. The wound-healing rate, epithelialization, angiogenesis, and collagen deposition were assessed after treatment and corroborated in vitro. Our study demonstrated that m/NP/miR-21 can promote wound healing in terms of epithelialization, dermal reconstruction, and neovascularization, and it can regulate the corresponding functions of keratinocytes, fibroblasts, and vascular endothelial cells. m/NP/miR-21 can inhibit the expression of PTEN, a gene downstream of miR-21, and increase the phosphorylation activation of AKT, which can then regulate the functions of fibroblasts. In conclusion, this provides a new approach to therapy for skin wounds using microRNA transporters and biomimetic nanoparticles.
微小RNA(miRNAs)已被证明参与多种生理和病理过程的调控,但由于其不稳定性,它们在疾病治疗中的应用仍然有限。仿生纳米材料将纳米材料与易于修饰且具有生物相容性的细胞成分相结合,使其成为一种新兴的微小RNA递送载体。在本研究中,通过共挤出将脂肪来源的间充质干细胞(MSC)膜包裹在负载有miR-21的聚乳酸-乙醇酸共聚物-聚乙烯亚胺(PLGA-PEI)周围,随后移植到C57BL/6小鼠伤口中。治疗后评估伤口愈合率、上皮化、血管生成和胶原沉积,并在体外得到证实。我们的研究表明,m/NP/miR-21在促进上皮化、真皮重建和新生血管形成方面可促进伤口愈合,并且可以调节角质形成细胞、成纤维细胞和血管内皮细胞的相应功能。m/NP/miR-21可以抑制miR-21下游的磷酸酶和张力蛋白同源物(PTEN)的表达,并增加蛋白激酶B(AKT)的磷酸化激活,进而调节成纤维细胞的功能。总之,这为使用微小RNA转运体和仿生纳米颗粒治疗皮肤伤口提供了一种新方法。