Rational design of nanotherapy for ulcerative colitis: New strategies, mechanistic approaches, and translational challenges.

Ulcerative colitis (UC), a chronic mucosal inflammatory condition, is hampered by the systemic side effects, variable responses, and limited sustained efficacy of current drugs like immunosuppressants and biologics. Recent advancements in nanotechnology have led to the emergence of groundbreaking drug delivery platforms, which offer new avenues for addressing the therapeutic challenges of UC. This article aims to provide a comprehensive review of the rational design principles underlying UC nanotherapeutics, with a focus on leveraging the unique pathophysiological features of the disease for the development of nanosystems endowed with dual-targeting capabilities and multi-stimulus responsiveness. We also discussed the multifaceted mechanisms of action of these nanotherapies, which extend beyond mere drug delivery to include immunomodulation, gut barrier repair, and gut microbiota remodeling. Furthermore, the challenges in clinical translation are critically evaluated, encompassing biosafety, manufacturing quality, and the preclinical-human gap. This article would serve as a resource for understanding nanotherapies for UC.