2. Academic Validation
  3. Regenerating aged bone marrow via a nitric oxide nanopump

Regenerating aged bone marrow via a nitric oxide nanopump

  • Nat Commun. 2025 Jul 1;16(1):5677. doi: 10.1038/s41467-025-61256-5.
Ke Li # 1 2 3,  Sihan Hu # 1 3,  Hanwen Li # 2 3,  Wenzheng Lin 1 2 3,  Duoyi Zhao 1 2 3,  Zhuobin Xu 1 3,  Chun Pan 1 3,  Huihui Wang 1 3,  Dandan Li 1 3,  Jingjing Liu 4 5,  Hao Chen 6 7 8
Affiliations

Affiliations

  • 1 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.
  • 2 Department of Orthopedic, Affiliated Hospital of Yangzhou University, Yangzhou, China.
  • 3 The Key Laboratory of the Jiangsu Higher Education Institutions for Nucleic Acid & Cell Fate Regulation, Yangzhou, China.
  • 4 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. jjliu0105@yzu.edu.cn.
  • 5 The Key Laboratory of the Jiangsu Higher Education Institutions for Nucleic Acid & Cell Fate Regulation, Yangzhou, China. jjliu0105@yzu.edu.cn.
  • 6 Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China. hchen2020@yzu.edu.cn.
  • 7 Department of Orthopedic, Affiliated Hospital of Yangzhou University, Yangzhou, China. hchen2020@yzu.edu.cn.
  • 8 The Key Laboratory of the Jiangsu Higher Education Institutions for Nucleic Acid & Cell Fate Regulation, Yangzhou, China. hchen2020@yzu.edu.cn.
  • # Contributed equally.
PMID: 40593809 DOI: 10.1038/s41467-025-61256-5
Abstract

Resident leptin-receptor-expressing (LepR+) cells senescence in the aged bone marrow impairs the regenerative capacity of osteo- and Other lineages of cells. In this study, a LepR+ cell-targeting nitric oxide (NO) nanopump with in vivo self-controlled turn-on ability was constructed to rejuvenate the LepR+ cells in the aged bone marrow. The nanopump co-entrapped hydrophobic chemiluminescence substrate and NO donor into the matrix of amphiphilic polymer through a nanoprecipitation process. The chemiluminescence substrate in the NO nanopump automatically reacts with the accumulated H2O2 in the aged bone marrow and then directly transfers the chemical energy to the NO donor to induce in situ NO release. The NO produced in situ within the aged bone marrow triggered the regeneration of the osteoblastic and the Other niches in vivo through activating the glycolysis signaling in the senescent LepR+ cells. Conclusively, the constructed NO nanopump is a promising tool to counter aging-induced bone marrow disorders.

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