Keywords
Lipid nanoparticles, tendinopathy, siRNA, mRNA, regeneration
Authors
Sandra López-Cerdá, Giuseppina Molinaro, Rubén Pareja Tello, Alexandra Correia, Eero Waris, Jouni Hirvonen, Goncalo Barreto, Hélder A. Santos
Abstract
Tendinopathy involves the inflammation and degeneration of the tendon due to repetitive strain injury. Currenttreatments primarily target inflammation resolution, yet they do not aim at tissue regeneration. In this study, a microfluidicsapproach is harnessed to develop a platform of lipid nanoparticles (LNPs) loaded simultaneously with SMAD3 siRNA and collagen ImRNA, aiming to explore its potential dual antifibrotic and regenerative effects in human tenocytes. The developed LNPs displayedsize homogeneity and colloidal stability and exhibited high cytocompatibility in human tenocytes. Moreover, LNPs allowed forefficient uptake and transfection efficiency of the RNAs. In the in vitro efficacy studies, the gene expression and production ofSMAD3 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 andpromote tissue remodeling in late stages of tendon diseases was confirmed.