ROS-sensitive Crocin-loaded chitosan microspheres for lung targeting and attenuation of radiation-induced lung injury.

Radiation-induced lung injury (RILI) is one of the major complications in patients exposed to accidental radiation and radiotherapy for thoracic malignancies. However, there is no reliable radioprotector for effective clinical treatment of RILI so far. Herein, a novel Crocin-loaded chitosan microsphere is developed for lung targeting and attenuation of RILI. The chitosan microspheres are modified with 4-carboxyphenylboronic acid and loaded with the natural antioxidant Crocin-I to give the drug-loaded microspheres (~10 μm). The microspheres possess good biocompatibility in vivo and in vitro. In a mouse model, they exhibit effective passive targeting performance and a long retention time in the lung after intravenous administration. Furthermore, they improve the radioprotective effect of Crocin-I for the treatment of RILI by reducing the level of inflammatory cytokines in bronchoalveolar lavage fluid and by regulating oxidative stress in lung tissues. The targeted agents significantly improved the bioavailability and radioprotection of Crocin-I by the outstanding passive targeting effect. This work may provide a promising strategy for efficient radioprotection on RILI using passive lung targeting microspheres.