Advances and prospects of microenvironment-targeted nanotherapeutics for ulcerative colitis: evolving paradigms in the precision gut microenvironment.

Ulcerative colitis (UC) manifests as a chronic inflammatory disorder of the colorectum, where dysregulated immunity arising from imbalances in the gut microenvironment drives recurrent tissue damage. Current clinical interventions remain restricted to symptoms without addressing core pathomechanistic circuits. Although widely used, conventional pharmacotherapies (including 5-aminosalicylic acid, corticosteroids, and immunosuppressants) face persistent challenges, including inadequate bioavailability, poor lesion targeting, and systemic toxicity. These challenges are compounded by gastrointestinal physiological barriers and UC-specific pathologies, which collectively undermine conventional oral therapies. Nanodrug delivery systems have consequently emerged as transformative solutions, demonstrating superior site-specific accumulation, enhanced bioavailability, and reduced off-target effects. Against this backdrop, this review systematically examines the pathological cascade initiated by microenvironment disruption while integrating nanotechnology innovations, highlights advanced targeting approaches responsive to inflammatory cues, and maps clinical translation pathways.