Navigating a thorny path: oral nanomedicines for the precision management of radiation-induced intestinal injury

Radiation-induced intestinal injury (RIII) is a severe complication that significantly compromises the quality of life and treatment outcomes in patients undergoing abdominal or pelvic radiotherapy. Despite recent advances in therapeutic strategies, conventional interventions often exhibit limited efficacy due to poor targeting, systemic side effects, and the complex pathophysiology of intestinal radiation damage. Oral nanomedicines have emerged as a promising platform, offering site-specific delivery, improved bioavailability, and enhanced mucosal protection, thereby holding unique advantages in the precise management of RIII. This review first provides a comprehensive overview of the molecular mechanisms underlying RIII and explores the intrinsic challenges that contribute to its therapeutic intractability. Guided by these mechanistic insights, we then discuss the rational design of oral nanomedicine systems tailored to mitigate radiation-induced intestinal damage. Furthermore, we highlight the translational potential of these nanoplatforms and introduce a novel concept-self-powered nanogenerators-for localized and sustained therapeutic modulation in RIII. Together, these strategies open new avenues for rethinking gastrointestinal radioprotection through the lens of precision nanomedicine.