1. Academic Validation
  2. Biomimetic targeted self-adaptive nanodrug for inflammation optimization and AT2 cell modulation in precise ARDS therapy

Biomimetic targeted self-adaptive nanodrug for inflammation optimization and AT2 cell modulation in precise ARDS therapy

  • Sci Adv. 2025 Aug;11(31):eadw5133. doi: 10.1126/sciadv.adw5133.
Cheng Chen 1 2 3 Danfeng He 2 4 Xilan Li 2 Zelin Ou 2 5 Hong Wang 2 Zhinan Shou 3 Li Wang 1 Zhengwei Mao 2 6 Xiaolan Qi 1 Jun Deng 2 4
Affiliations

Affiliations

  • 1 Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology of Guizhou Province, Guizhou Medical University, Guiyang 550004, China.
  • 2 Institute of Burn Research, Southwest Hospital, State Key Lab of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University of Chinese P.L.A.), Chongqing 400038 China.
  • 3 Department of Respiratory and Critical Care Medicine, The First People's Hospital of Guiyang, Guiyang 550002, China.
  • 4 Medical Imaging Key Laboratory of Sichuan Province, North Sichuan Medical College, Nanchong, Sichuan 637000, China.
  • 5 Department of Dermatology, Children' s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
  • 6 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310058, China.
Abstract

Acute respiratory distress syndrome (ARDS) is a lethal respiratory condition, while effective pharmacological treatments remain elusive. We identified the decreased mechanical capacity and impaired proliferation of alveolar type 2 (AT2) epithelial cells in the inflammatory environment as the primary contributors to respiratory failure of ARDS. A biomimetic, self-adaptive, 7,8-dihydroxyflavone-loaded hollow mesoporous cerium oxide coated with a platelet membrane (HCeOx-D@PM) was developed for precise ARDS therapy. HCeOx-D@PM comprises a platelet membrane (PM) shell for targeted delivery to injured lungs and an HCeOx core, which enables high drug loading, efficient Reactive Oxygen Species (ROS) scavenging, and penetration of the alveolar-capillary barrier. Initially, HCeOx-D@PM suppresses the inflammation and mitigates the adverse effects of lesions on AT2 cell by scavenging accumulated ROS. It then adaptively releases 7,8-dihydroxyflavone in response to cysteine-aspartic acid protease 3 activation, facilitating AT2 cell proliferation and notably improving survival rates in vivo, offering a promising advancement in the precise treatment of respiratory diseases.

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