2. Academic Validation
  3. Identification of splenic IRF7 as a nanotherapy target for tele-conditioning myocardial reperfusion injury

Identification of splenic IRF7 as a nanotherapy target for tele-conditioning myocardial reperfusion injury

  • Nat Commun. 2025 Feb 24;16(1):1909. doi: 10.1038/s41467-025-57048-6.
Qiang Long 1,  Kristina Rabi 2,  Yu Cai 3,  Lihui Li 1,  Shixing Huang 1,  Bei Qian 1,  Yiming Zhong 1,  Zhaoxi Qi 1,  Yecen Zhang 1,  Kaichen Huang 1,  Xinming Wang 1,  Lan Chang 1,  Weichang Xie 1,  Huaiyu Jiang 1,  Haonan Zhang 1,  Junjie Zhang 1,  Ting Ren 1,  Zichen Wang 1,  Tambet Teesalu 2,  Caisheng Wu 3,  Lin Lu 4,  Zhengbin Zhu 4,  Yiwei Chu 5,  Hélder A Santos 6 7,  Zehua Liu 8 9,  Qiang Zhao 10,  Xiaofeng Ye 11
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Laboratory of Precision and Nanomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
  • 3 Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
  • 4 Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 Department of Immunology, School of Basic Medical Sciences, Biotherapy Research Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • 6 Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
  • 7 Department of Biomaterials and Biomedical Technology, The Personalized Medicine Research Institute (PRECISION), University Medical Center Groningen, University of Groningen (UMCG), AV, Groningen, Netherlands.
  • 8 Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. zehua.liu@helsinki.fi.
  • 9 Department of Biomaterials and Biomedical Technology, The Personalized Medicine Research Institute (PRECISION), University Medical Center Groningen, University of Groningen (UMCG), AV, Groningen, Netherlands. zehua.liu@helsinki.fi.
  • 10 Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. zq11607@rjh.com.cn.
  • 11 Department of Cardiovascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. xiaofengye@hotmail.com.
PMID: 39994192 DOI: 10.1038/s41467-025-57048-6
Abstract

The sequestration of nanoparticles by mononuclear phagocyte system is a challenge for the use of nanotherapy for treating cardiovascular diseases due to the conventionally perceived loss of therapeutic potency. Here, we revitalize cardiovascular nanotherapy by unlocking an alternative route in which nanomedicines are redirected to the spleen, leveraging its potential as a highly efficient and targeted site for remote conditioning, or tele-conditioning myocardial reperfusion injury. The theoretical foundation underpinning is the splenogenic nature of recruited monocytes upon myocardial reperfusion in the acute stage, which is confirmed through murine heterotopic spleen transplantation. Single-cell RNA-seq analysis identifies IRF7 as a pivotal mediator in the spleen-heart communication network that is initially induced in the spleen and orchestrates functional changes in myocardial macrophages. Spleen-related induction of IRF7 is also valid in human myocardial reperfusion scenarios. In addition, in a murine preclinical model of male mice, temporal inhibition of splenic IRF7 through the designed spleen-targeting erythrosome engineered with the targeting peptide RP182, termed as STEER nanoparticles, mitigates the acute-stage innate immune responses and improves the cardiac function in the long term. In contrast, systemic inhibition, genetic knockout of IRF7 or absolute depletion of splenic monocytes does not have therapeutic benefits, indicating the superiority of nanoparticle-based targeted treatment. These findings establish the spleen as a naturally favored site for nanoparticle-based treatments, offering promising avenues for managing myocardial reperfusion injury.

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