Immune cell-targeted nanocarrier delivery systems for inflammatory bowel disease therapy: mechanisms and strategies.

Abstract

Inflammatory bowel disease (IBD) is a chronic intestinal disorder caused by immune dysregulation, leading to persistent inflammation and recruiting a large number of immune cells to the intestinal inflammation sites. When immune cells become aberrantly activated, macrophages, neutrophils, dendritic cells, T cells and B cells infiltrate affected intestinal sites, releasing pro-inflammatory cytokines that amplify tissue damage and perpetuate disease progression. Base on pathological mechanisms, immune cell-targeted nanocarrier systems have emerged as innovative platforms for precise drug delivery to inflamed colonic regions, minimizing off-target effects, regulating immune imbalance and enhancing therapeutic efficacy. This review systematically examines the roles of key immune cells and their associated signaling pathways in IBD pathogenesis, with a particular focus on immune regulatory mechanisms at inflammatory foci. Furthermore, it explores design strategies for nanoparticles functionalized with specific ligands, including mannose, folic acid, lactoferrin, and hyaluronic acid, which facilitate selective targeting of immune cells. These modifications optimize immune cell phenotype modulation, cytokine secretion control, and tissue repair, significantly reducing systemic toxicity and improving drug bioavailability. Finally, challenges and future perspectives, including ligand specificity optimization, clinical translation barriers, and multifunctional nanoparticle development, are discussed to advance IBD treatment paradigms. Collectively, this comprehensive summary of immune cell-targeted nanotherapeutics provides novel insights into precision treatment strategies for IBD, paving the way for more effective and targeted therapeutic interventions.