1. Lung-Targeting Perylenediimide Nanocomposites for Efficient Therapy of Idiopathic Pulmonary Fibrosis.
- Author
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Liu Y, Xu D, Xing X, Shen A, Jin X, Li S, Liu Z, Wang L, and Huang Y
- Subjects
- Animals, Mice, Humans, Bleomycin, Transforming Growth Factor beta1 metabolism, Idiopathic Pulmonary Fibrosis drug therapy, Idiopathic Pulmonary Fibrosis pathology, Imides chemistry, Imides pharmacology, Perylene analogs & derivatives, Perylene chemistry, Perylene pharmacology, Perylene therapeutic use, Lung drug effects, Lung pathology, Lung metabolism, Nanocomposites chemistry, Nanocomposites therapeutic use
- Abstract
Idiopathic pulmonary fibrosis, an idiopathic interstitial lung disease with high mortality, remains challenging to treat due to the lack of clinically approved lung-targeting drugs. Herein, we present PDIC-DPC, a perylenediimide derivative that exhibits superior lung-selective enrichment. PDIC-DPC forms nanocomposites with plasma proteins, including fibrinogen beta chain and vitronectin, which bind to pulmonary endothelial receptors for lung-specific accumulation. Moreover, PDIC-DPC significantly suppresses transforming growth factor beta1 and activates adenosine monophosphate-activated protein kinase. As a result, compared to existing therapeutic drugs, PDIC-DPC achieves superior therapeutic outcomes, evidenced by the lowest Ashcroft score, significantly improved pulmonary function, and an extended survival rate in a bleomycin-induced pulmonary fibrosis model. This study elucidates the lung-selective enrichment of assembled prodrug from biological perspectives and affords a platform enabling therapeutic efficiency on idiopathic pulmonary fibrosis.
- Published
- 2024
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