Identification of Splenic IRF7 as a Nanotherapy Target for Tele-Conditioning Myocardial Reperfusion Injury
I Can Do It with a Broken Heart
In an interesting twist in cardiovascular research, scientists from University Medical Center Groningen led by Prof. Hélder A: Santos, the University of Helsinki led by Dr. Zehua Liu, and Shanghai JiaoTong University led by Prof. Xiaofeng Ye, have discovered that the spleen, an often-overlooked immune organ, might hold the key to protecting the heart from damage after a heart attack.
Published recently in Nature Communications, this study reveals a novel strategy to reduce heart injury using nanotherapy that targets a specific immune response pathway in the spleen. Researchers have demonstrated that by focusing on the spleen, they can prevent excessive immune responses that worsen heart damage during myocardial reperfusion injury, a condition that occurs when blood flow is restored after a blockage, often leading to further tissue damage.
Turning a Biological Obstacle Into an Advantage
One of the major challenges in using nanotherapy to treat heart conditions has been the body’s natural defense system. Typically, nanoparticles designed to deliver drugs to the heart are intercepted by the body’s mononuclear phagocyte system (MPS), especially by the spleen and liver, before they can reach their target.
If you cannot bypass it, you have to embrace it. Researcher found that the spleen plays a critical role in supplying immune cells, particularly monocytes, which can contribute to heart inflammation following a heart attack. By targeting these monocytes before they travel to the heart, the team discovered a way to limit inflammation and promote better recovery.
IRF7: The Immune System’s Silent Conductor
At the core of this discovery is a gene regulator called interferon regulatory factor 7 (IRF7). Known for its role in controlling immune responses, IRF7 becomes highly active in the spleen shortly after a heart attack, triggering a cascade of inflammatory signals that can worsen heart damage.
The researchers realized that by blocking IRF7 activation in the spleen, they could disrupt this harmful immune signaling pathway, before it even reaches the heart.
STEER the wheel
To harness this finding, the team developed a nanotherapy system named STEER nanoparticles. These specially designed nanoparticles are engineered to deliver a small-molecule inhibitor (HS38) directly to the spleen, suppressing IRF7 activity without compromising the body’s overall immune function.
In preclinical trials using mice, a single injection of STEER nanoparticles significantly reduced heart damage following simulated heart attacks. Unlike conventional methods that often focus on directly targeting the heart, this innovative approach works remotely, intercepting harmful immune responses at their source.
Why This Matters
Heart disease remains the leading cause of death globally, and despite advances in treatment, many heart attack survivors face long-term complications due to tissue damage caused by inflammation. This discovery opens up a promising new pathway for developing therapies that prevent heart damage at the source, by modulating immune responses before they can harm cardiac tissue.
The team’s findings also suggest potential applications beyond heart disease. Since IRF7 plays a central role in various immune processes, this approach could be adapted to treat other inflammatory conditions, offering a broader impact on medicine.
What’s Next?
While these results are promising, further research is needed before this therapy can be applied to humans. Future studies will focus on testing the safety and effectiveness of STEER nanoparticles in clinical settings.
This innovative work doesn’t just change how scientists think about treating heart attacks, it reimagines how the immune system can be guided to heal rather than harm. By transforming the spleen from a barrier into an ally, researchers have opened a new frontier in cardiovascular therapy.
The article is available free of charge in Nature Communications at https://doi.org/10.1038/s41467-025-57048-6
Contact information:
Prof. Hélder A. Santos, Department of Biomaterials and Biomedical Technology
[email protected]
Building 3215 (FB40), 1317
9713 AV Groningen, the Netherlands
