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

Qiang Long, Kristina Rabi, Yu Cai, Lihui Li, Shixing Huang, Bei Qian, Yiming Zhong, Zhaoxi Qi, Yecen Zhang, Kaichen Huang, Xinming Wang, Lan Chang, Weichang Xie, Huaiyu Jiang, Haonan Zhang, Junjie Zhang, Ting Ren, Zichen Wang, Tambet Teesalu, Caisheng Wu, Lin Lu, Zhengbin Zhu, Yiwei Chu, Hélder A. Santos, Zehua Liu (), Qiang Zhao () and Xiaofeng Ye ()
Additional contact information
Qiang Long: Shanghai Jiao Tong University School of Medicine
Kristina Rabi: University of Tartu
Yu Cai: Xiamen University
Lihui Li: Shanghai Jiao Tong University School of Medicine
Shixing Huang: Shanghai Jiao Tong University School of Medicine
Bei Qian: Shanghai Jiao Tong University School of Medicine
Yiming Zhong: Shanghai Jiao Tong University School of Medicine
Zhaoxi Qi: Shanghai Jiao Tong University School of Medicine
Yecen Zhang: Shanghai Jiao Tong University School of Medicine
Kaichen Huang: Shanghai Jiao Tong University School of Medicine
Xinming Wang: Shanghai Jiao Tong University School of Medicine
Lan Chang: Shanghai Jiao Tong University School of Medicine
Weichang Xie: Shanghai Jiao Tong University School of Medicine
Huaiyu Jiang: Shanghai Jiao Tong University School of Medicine
Haonan Zhang: Shanghai Jiao Tong University School of Medicine
Junjie Zhang: Shanghai Jiao Tong University School of Medicine
Ting Ren: Shanghai Jiao Tong University School of Medicine
Zichen Wang: Shanghai Jiao Tong University School of Medicine
Tambet Teesalu: University of Tartu
Caisheng Wu: Xiamen University
Lin Lu: Shanghai Jiao Tong University School of Medicine
Zhengbin Zhu: Shanghai Jiao Tong University School of Medicine
Yiwei Chu: Fudan University
Hélder A. Santos: University of Helsinki
Zehua Liu: University of Helsinki
Qiang Zhao: Shanghai Jiao Tong University School of Medicine
Xiaofeng Ye: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-57048-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57048-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-57048-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().