Novel Nanoparticle Approach to Mitigate Radiotherapy-Induced Bowel Injury and Secondary Colorectal Cancer
Background and aims Radiotherapy for abdominal and pelvic tumors is frequently compromised by intestinal injuries and secondary malignancies, especially colorectal tumors. Existing protective approaches focus mainly on epithelial restoration, inadequately addressing microbiota disruption and immune dysregulation. This study aimed to develop a nanoparticle formulation to specifically protect the colorectal region during radiotherapy, alleviating bowel injury without compromising tumor control. Methods Chitosan-encapsulated pectin-amifostine (CS/PEC-AMF) nanoparticles were orally administered to mice undergoing abdominopelvic irradiation. Protective effects on intestinal injury, microbiota, mucosal immunity, tumor regression, and carcinogenesis were assessed through histopathological evaluation, survival analysis, tumor growth monitoring, and mRNA sequencing. Results CS/PEC-AMF nanoparticles selectively released amifostine in the colorectal region, significantly reducing reactive oxygen species, protecting healthy cells, restoring microbiota balance, and regulating mucosal immune homeostasis. In murine models, nanoparticles effectively mitigated acute and chronic radiation-induced intestinal injuries, enhanced tumor suppression, extended survival in orthotopic colon and rectal tumor-bearing mice undergoing radiotherapy, and reduced colorectal tumor incidence in AOM/DSS-exposed mice. Transcriptomic analysis confirmed inhibition of cytokine storms and enhanced DNA repair pathways. Conclusion CS/PEC-AMF nanoparticles provide a targeted and effective strategy to mitigate radiation-induced bowel injury and secondary malignancies while enhancing therapeutic efficacy in abdominal and pelvic radiotherapy.