Oral administration amifostine-grafted chitosan nanodrug for intestinal radioprotection

Ionizing radiation from accidental exposure or planned radiotherapy can lead to irreparable damage to the gastrointestinal tract, especially the small intestine. There has been an unmet clinical need to protect the intestine from radiation-induced injury till now. Herein, we develop a strategy for efficient intestinal radioprotection by an oral administration amifostine-grafted chitosan nanodrug. Specifically, amifostine is grafted onto carboxymethyl chitosan by a facile one-pot synthesis. The nanodrug not only preserves the pH-responsive behavior and excellent biocompatibility from chitosan, but also enhances the oral bioavailability and reduces biological toxicity of amifostine. Compared with free amifostine, the strategy manifests significantly superior radioprotection for the small intestine. The nanodrug can prevent the radiation-induced intestinal injury and improve survival rates of mice exposed to lethal dose irradiation. It also maintains the gut microbiota homeostasis of the irradiated mice. This work provides a promising approach for effectively mitigating radiation-induced intestinal injury, and adds insights into decay and minimum side effects.