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

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.