Ran Yu, Yin Shanmei, Xie Pei, Liu Yaxue, Wang Ying, Yin Zongning
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Co-Construction Collaborative Innovation Center for Chinese Medicine Resources Industrialization by Shaanxi & Education Ministry, Shaanxi University of Chinese Medicine, Xianyang 712038, China.
Nanoscale. 2024 Jan 25;16(4):1983-1998. doi: 10.1039/d3nr04401g.
Acute lung injury (ALI) is an inflammatory disease caused by multiple factors such as infection, trauma, and chemicals. Without effective intervention during the early stages, it usually quickly progresses to acute respiratory distress syndrome (ARDS). Since ordinary pharmaceutical preparations cannot precisely target the lungs, their clinical application is limited. In response, we constructed a γ3 peptide-decorated and ROS-responsive nanoparticle system encapsulating therapeutic dexamethasone (Dex/PSB-γ3 NPs). , Dex/PSB-γ3 NPs had rapid HO responsiveness, low cytotoxicity, and strong intracellular ROS removal capacity. In a mouse model of ALI, Dex/PSB-γ3 NPs accumulated at the injured lung rapidly, alleviating pulmonary edema and cytokine levels significantly. The modification of NPs by γ3 peptide achieved highly specific positioning of NPs in the inflammatory area. The ROS-responsive release mechanism ensured the rapid release of therapeutic dexamethasone at the inflammatory site. This combined approach improves treatment accuracy, and drug bioavailability, and effectively inhibits inflammation progression. Our study could effectively reduce the risk of ALI progressing to ARDS and hold potential for the early treatment of ALI.
急性肺损伤（ALI）是一种由感染、创伤和化学物质等多种因素引起的炎症性疾病。如果在早期阶段没有进行有效干预，它通常会迅速发展为急性呼吸窘迫综合征（ARDS）。由于普通药物制剂无法精确靶向肺部，其临床应用受到限制。作为应对措施，我们构建了一种包裹治疗性地塞米松的γ3肽修饰且对活性氧（ROS）有响应的纳米颗粒系统（Dex/PSB-γ3 NPs）。Dex/PSB-γ3 NPs具有快速的HO响应性、低细胞毒性和强大的细胞内ROS清除能力。在ALI小鼠模型中，Dex/PSB-γ3 NPs迅速在损伤的肺部积聚，显著减轻肺水肿和细胞因子水平。通过γ3肽对纳米颗粒进行修饰，实现了纳米颗粒在炎症区域的高度特异性定位。ROS响应释放机制确保了治疗性地塞米松在炎症部位的快速释放。这种联合方法提高了治疗的准确性和药物生物利用度，并有效抑制炎症进展。我们的研究可以有效降低ALI发展为ARDS的风险，并为ALI的早期治疗带来潜力。
