Mannosylated polydopamine nanoparticles alleviate radiation- induced pulmonary fibrosis by targeting M2 macrophages and inhibiting the TGF-β1/Smad3 signaling pathway

Radiation-induced pulmonary fibrosis (RIPF), one type of pulmonary interstitial diseases, is frequently observed following radiation therapy for chest cancer or accidental radiation exposure. Current treatments against RIPF frequently fail to target lung effectively and the inhalation therapy is hard to penetrate airway mucus. Therefore, this study synthesized mannosylated polydopamine nanoparticles (MPDA NPs) through one-pot method to treat RIPF. Mannose was devised to target M2 macrophages in the lung through CD 206 receptor. MPDA NPs showed higher efficiency of penetrating mucus, cellular uptake and ROS-scavenging than original polydopamine nanoparticles (PDA NPs) in vitro. In RIPF mice, aerosol administration of MPDA NPs significantly alleviated the inflammatory, collagen deposition and fibrosis. The western blot analysis demonstrated that MPDA NPs inhibited TGF-β1/Smad3 signaling pathway against pulmonary fibrosis. Taken together this study provide a novel M2 macrophages-targeting nanodrugs through aerosol delivery for the prevention and targeted treatment for RIPF.