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Peer-reviewedCC BYAdvanced science (Weinheim, Baden-Wurttemberg, Germany)

Ultrasound-Triggered piRNA Delivery Using Biomimetic Phase-Changeable Nanoparticles for Theranostics of Myocardial Infarction.

  • Yajun Zhang1
  • Hongzhao Qi2
  • Yanyan Yang3
  • Feng Wang4
  • Tiantian Han1
  • Yanbei Lei5
  • Xiaolu Li1
  • Zhibin Wang1
  • Hua Qu6
  • Tao Yu1,2
  • Pin Sun1
6 affiliations
  1. 1Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.
  2. 2Department of Vascular Biology and Translational Medicine, Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.
  3. 3Department of Immunology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, People's Republic of China.
  4. 4Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.
  5. 5Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.
  6. 6Institute of Clinical Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China.
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Abstract

Myocardial infarction (MI) remains a major cause of cardiovascular morbidity, and effective strategies to prevent adverse remodeling are limited. Here, we identify piR-1873 as a cardioprotective piRNA that is down-regulated in MI patients, mouse models, and H₂O₂-treated cardiomyocytes. Serum piR-1873 levels correlated with MI biomarkers, suggesting its potential as a complementary biomarker, with an area under the curve (AUC) of 0.8389. Mechanistically, piR-1873 directly targeted Usp2 and inhibited RIP1/RIP3/MLKL-mediated necroptosis. To achieve efficient delivery, we developed ultrasound (US)-responsive piRNA nanoparticles (piR-NPs) consisting of a perfluorohexane (PFH) phase-change core loaded with piR-1873 and coated with a cardiomyocyte membrane shell. In vitro, piR-NPs enhanced piR-1873 delivery and suppressed cardiomyocyte necroptosis, with US further improving these effects. In MI mice, piR-NPs accumulated in infarcted myocardium, and US enhanced nanoparticle retention, resulting in improved cardiac function, reduced fibrosis, and attenuated necroptosis without detectable systemic toxicity. Collectively, this study reveals the diagnostic and therapeutic potential of piR-1873 and establishes a biomimetic, US-triggered piRNA delivery platform for MI treatment.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026ultrasoundtriggered,
  title = {{Ultrasound-Triggered piRNA Delivery Using Biomimetic Phase-Changeable Nanoparticles for Theranostics of Myocardial Infarction.}},
  author = {Yajun Zhang and Hongzhao Qi and Yanyan Yang and Feng Wang and Tiantian Han and Yanbei Lei and Xiaolu Li and Zhibin Wang and Hua Qu and Tao Yu and Pin Sun},
  journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.78282},
  url = {https://europepmc.org/article/MED/42875824},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Ultrasound-Triggered piRNA Delivery Using Biomimetic Phase-Changeable Nanoparticles for Theranostics of Myocardial Infarction.
AU  - Yajun Zhang
AU  - Hongzhao Qi
AU  - Yanyan Yang
AU  - Feng Wang
AU  - Tiantian Han
AU  - Yanbei Lei
AU  - Xiaolu Li
AU  - Zhibin Wang
AU  - Hua Qu
AU  - Tao Yu
AU  - Pin Sun
PY  - 2026
DA  - 2026/10/14
JO  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO  - 10.1002/advs.78282
UR  - https://europepmc.org/article/MED/42875824
AB  - Myocardial infarction (MI) remains a major cause of cardiovascular morbidity, and effective strategies to prevent adverse remodeling are limited. Here, we identify piR-1873 as a cardioprotective piRNA that is down-regulated in MI patients, mouse models, and H₂O₂-treated cardiomyocytes. Serum piR-1873 levels correlated with MI biomarkers, suggesting its potential as a complementary biomarker, with an area under the curve (AUC) of 0.8389. Mechanistically, piR-1873 directly targeted Usp2 and inhibited RIP1/RIP3/MLKL-mediated necroptosis. To achieve efficient delivery, we developed ultrasound (US)-responsive piRNA nanoparticles (piR-NPs) consisting of a perfluorohexane (PFH) phase-change core loaded with piR-1873 and coated with a cardiomyocyte membrane shell. In vitro, piR-NPs enhanced piR-1873 delivery and suppressed cardiomyocyte necroptosis, with US further improving these effects. In MI mice, piR-NPs accumulated in infarcted myocardium, and US enhanced nanoparticle retention, resulting in improved cardiac function, reduced fibrosis, and attenuated necroptosis without detectable systemic toxicity. Collectively, this study reveals the diagnostic and therapeutic potential of piR-1873 and establishes a biomimetic, US-triggered piRNA delivery platform for MI treatment.
SN  - 2198-3844
ER  -