A Lung-Targeted Carrier of Carbon Monoxide for Idiopathic Pulmonary Fibrosis Therapy

作者：Wenyu Guo, Shuo Huang, Jiabin Zhang, Jiabin Zhang, Xi Zhang, Jinyu Yang, Yunlong Bao, Jue Zhang, Jue Zhang · 发表于：ACS Nano · 年份：2026 · DOI：10.1021/acsnano.6c01762 · 被引用次数：1 · 研究领域：Heme Oxygenase-1 and Carbon Monoxide、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Inhalation and Respiratory Drug Delivery

Idiopathic Pulmonary Fibrosis (IPF) is a severely irreversible chronic disease affecting approximately 3 million individuals worldwide, with its pathogenic mechanisms remaining incompletely elucidated. Currently, treatment options of IPF are very limited, with only two FDA-approved drugs. The development of innovative therapeutics and advanced delivery technologies represents a pivotal step to overcoming the current clinical challenges of IPF. CO-based gas therapy is recognized as a potential IPF therapeutic strategy. However, a safe and efficient delivery of CO to pulmonary fibrosis tissue remains a challenge, constraining advancements in this field. To address the above issues, a lung-targeted carrier of CO (LTCoCO) was developed in this study by directly encapsulating CO within phospholipid microspheres, leveraging size-dependent pulmonary retention and selective organ targeting (SORT) principles. By regulating the TGF-β1/Smad signaling pathway and exerting anti-inflammatory, antioxidant, and antifibrotic activities, LTCoCOs have demonstrated in vivo inhibition of IPF, resulting in significant recovery from bleomycin-induced pulmonary fibrosis. Mechanistic in vitro studies identified LTCoCOs as potent inhibitors of epithelial-mesenchymal transition (EMT), endothelial-to-mesenchymal transition (E(nd)MT), and fibroblast activation (FA), acting through both canonical and noncanonical TGF-β1 pathways to achieve robust antifibrotic effects. In summary, an LTCoCO-based strategy ...