Yanhong Zhang, Yi Zhao, Ping Xu, Chao Zhang, Xiaokai Chen, Jing Guo, Bin He, Yan Liang
Inflammatory bowel disease (IBD), a chronic gastrointestinal disorder with rising colorectal cancer risks, faces treatment challenges due to nonspecific drug delivery and systemic side effects. Recent advances focus on stimuli-responsive nanomaterials that enable targeted drug release at inflamed sites while sparing healthy tissues. This review examines progress in IBD nanotherapy over five years, first outlining IBD's pathophysiology and intestinal microenvironment. It systematically details nanomaterial designs responsive to internal triggers (pH, ROS/redox, enzymes) and external stimuli (temperature, light), as well as dual/multi-responsive systems that enhance tissue-nanocarrier interactions for precise drug targeting. These smart systems improve therapeutic efficacy by leveraging IBD-specific inflammatory signals to control drug release. The discussion extends to emerging strategies combining multiple stimuli to address IBD's complex microenvironment. While promising, challenges remain in optimizing biocompatibility, scale-up production, and clinical translation. Future opportunities lie in personalized nanotherapy and integration with diagnostics, potentially revolutionizing IBD management through enhanced specificity and reduced side effects.