Lung-Targeting\nPerylenediimide Nanocomposites for\nEfficient Therapy of Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis, an idiopathic interstitial\nlung\ndisease with high mortality, remains challenging to treat due to the\nlack of clinically approved lung-targeting drugs. Herein, we present\nPDIC-DPC, a perylenediimide derivative that exhibits superior lung-selective\nenrichment. PDIC-DPC forms nanocomposites with plasma proteins, including\nfibrinogen beta chain and vitronectin, which bind to pulmonary endothelial\nreceptors for lung-specific accumulation. Moreover, PDIC-DPC significantly\nsuppresses transforming growth factor beta1 and activates adenosine\nmonophosphate-activated protein kinase. As a result, compared to existing\ntherapeutic drugs, PDIC-DPC achieves superior therapeutic outcomes,\nevidenced by the lowest Ashcroft score, significantly improved pulmonary\nfunction, and an extended survival rate in a bleomycin-induced pulmonary\nfibrosis model. This study elucidates the lung-selective enrichment\nof assembled prodrug from biological perspectives and affords a platform\nenabling therapeutic efficiency on idiopathic pulmonary fibrosis.