López-Cerdá Sandra, Molinaro Giuseppina, Tello Rubén Pareja, Correia Alexandra, Waris Eero, Hirvonen Jouni, Barreto Goncalo, Santos Hélder A
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland.
Department of Hand Surgery, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland.
ACS Appl Nano Mater. 2024 Jul 18;7(15):17736-17747. doi: 10.1021/acsanm.4c02996. eCollection 2024 Aug 9.
Tendinopathy involves the inflammation and degeneration of the tendon due to repetitive strain injury. Current treatments primarily target inflammation resolution, yet they do not aim at tissue regeneration. In this study, a microfluidics approach is harnessed to develop a platform of lipid nanoparticles (LNPs) loaded simultaneously with SMAD3 siRNA and collagen I mRNA, aiming to explore its potential dual antifibrotic and regenerative effects in human tenocytes. The developed LNPs displayed size homogeneity and colloidal stability and exhibited high cytocompatibility in human tenocytes. Moreover, LNPs allowed for efficient uptake and transfection efficiency of the RNAs. In the efficacy studies, the gene expression and production of SMAD3 and collagen I were tested by real-time quantitative chain polymerase reaction and immuno- and intracellular staining, revealing collagen I production enhancement, SMAD3 inhibition, and modulation of other tendon repair factors by the LNPs. Overall, the potential of this platform of RNA-loaded LNPs to be used as a dual therapeutic approach to prevent fibrosis and promote tissue remodeling in late stages of tendon diseases was confirmed.
肌腱病是由于反复劳损损伤导致肌腱发生炎症和退变。目前的治疗主要针对炎症的消退，但并不致力于组织再生。在本研究中，利用微流控方法开发了一种同时负载SMAD3小干扰RNA（siRNA）和I型胶原mRNA的脂质纳米颗粒（LNP）平台，旨在探索其在人肌腱细胞中潜在的双重抗纤维化和再生作用。所开发的LNP显示出大小均一性和胶体稳定性，并且在人肌腱细胞中表现出高细胞相容性。此外，LNP能够实现RNA的有效摄取和转染效率。在功效研究中，通过实时定量链聚合酶反应以及免疫和细胞内染色检测了SMAD3和I型胶原的基因表达及生成情况，结果显示LNP能够增强I型胶原生成、抑制SMAD3，并调节其他肌腱修复因子。总体而言，证实了这种负载RNA的LNP平台作为一种双重治疗方法用于预防肌腱疾病晚期纤维化和促进组织重塑的潜力。
