Pathological Mechanisms of Radiation-Induced Lung Injury and Novel Nano-Drug Delivery Therapeutic Strategies

Xiaohuo Zhang,1,* Zhiruo Zhang,2 Mi Huang,2 Yufan Jin,2 Youming Huang,2 Peng Ji,2,3,* Zhenchao Ma1,* 1Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, Zhejiang, 313000, People’s Republic of China; 2School of Pharmacy, Taizhou University, Taizhou, Jiangsu, 225300, People’s Republic of China; 3Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Ji, School of Pharmacy, Taizhou University, No. 93, Jichuan East Road, Taizhou, Jiangsu, 225300, People’s Republic of China, Email [email protected] Zhenchao Ma, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, No. 1558 North Sanhuan Road, Huzhou, Zhejiang, 313000, People’s Republic of China, Email [email protected]: Radiation-induced lung injury (RILI), encompassing early radiation pneumonitis (RP) and late radiation-induced lung fibrosis (RILF), remains a major dose-limiting complication of thoracic radiotherapy. The pathological processes involve oxidative stress, DNA damage, inflammatory cascades (notably IL-1, IL-6, TNF-α, and TGF-β), and fibrotic remodeling, yet current therapies—such as corticosteroids and antifibrotic agents—provide only partial relief and are often accompanied by significant side effects. Recent advances in nano-drug delivery systems (NDDS) offer new opportunities to overcome these limitations through targeted pulmonary delivery, stimuli-responsive release, and synergistic modulation of pathological pathways. Nanoformulations, including hyaluronic acid-based carriers, ROS-responsive microspheres, and inhalable nanomedicines, demonstrate enhanced pulmonary bioavailability, reduced systemic toxicity, and multi-mechanistic therapeutic potential. With continued refinement of intelligent nanocarriers and integration of advanced diagnostic tools, NDDS holds strong promise for translating preclinical advances into precise, individualized therapies for RILI.Keywords: radiation pneumonitis, radiation-induced lung injury, nano-drug delivery system, stimuli-responsive release, targeted drug delivery, lung-targeted nanomedicine