A Multimodal Therapeutic Strategy for Inflammatory Bowel Disease Using MicroRNA-146a Mimic Encapsulated in Lipid Nanoparticles

Abstract

Dysregulated microRNAs (miRNAs) have significant potential as diagnostic tools for various chronic diseases; however, their therapeutic applications remain largely unexplored. Given their capacity to regulate multiple pathways, miRNAs are promising candidates for treating pleiotropic diseases, such as inflammatory bowel disease (IBD). In our study, we conducted a comprehensive review of the literature of miRNA-146 levels in the inflamed tissues of IBD patients and murine colitis models. Initially, we quantified the expression of miRNA-146a and miRNA-146b in the colons of mice using the dextran sodium sulfate (DSS)-inducedacute model of IBD. We selected miRNA-146a for further study due to its anti-inflammatory properties and potential relevance in IBD treatment. We hypothesized that a macrophage model of inflammation would be well-suited to studying the effects of this miRNA. Subsequently, we investigated the use of lipid nanoparticles (LNPs) for the targeted delivery of miRNA-146a to macrophages, which play a key role in IBD. Our results indicated that miRNA-146a levels increased in the DSS model and LNP-mediated delivery effectively downregulated genes associated with inflammation. These findings highlight the critical role of miRNA-146a in modulating IBD and suggest that LNP-based delivery could be a promising therapeutic strategy for managing inflammatory responses.