| Autor: |
Hong, Guo, Jibin, Guan, Xian, Wu, Yushuang, Wei, Jiaqi, Zhao, Yan, Zhou, Faqian, Li, Hong-Bo, Pang |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Molecular Therapy. 31:875-889 |
| ISSN: |
1525-0016 |
| DOI: |
10.1016/j.ymthe.2023.01.003 |
| Popis: |
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are life-threatening conditions with excessive inflammation in the lung. Glucocorticoids had been widely used for ALI/ARDS, but their clinical benefit remains unclear. Here, we tackled the problem by conjugating prednisolone (PSL) with a targeting peptide termed CRV. Systemically administered CRV selectively homes to the inflamed lung of a murine ALI model, but not healthy organs or the lung of healthy mice. The expression of the CRV receptor, retinoid X receptor beta (RXRB), was elevated in the lung of ALI mice, and patients with interstitial lung diseases, which may be the basis of CRV targeting. Then we covalently conjugated PSL and CRV with a reactive oxygen species (ROS)-responsive linker in the middle. While being intact in blood, the ROS linker was cleaved intracellularly to release PSL for action. In vitro, CRV-PSL showed a similar anti-inflammatory effect to PSL. In vivo, CRV conjugation increased the amount of PSL in the inflamed lung but reduced its accumulation in healthy organs. Accordingly, CRV-PSL significantly reduced lung injury and immune-related side effects elsewhere. Taken together, our peptide-based strategy for targeted delivery of glucocorticoids for ALI may have a greater potential for clinical translation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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