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  3. Acoustic hydrogen delivery to treat PANoptosis induced by myocardial ischemia/reperfusion injury in rats

Acoustic hydrogen delivery to treat PANoptosis induced by myocardial ischemia/reperfusion injury in rats

  • Biomater Adv. 2026 Jun:183:214770. doi: 10.1016/j.bioadv.2026.214770.
Shu-Hui Wang 1,  Chen-Hui Li 1,  Zi-Jun Wei 2,  Cai-Yun Tang 2,  Yong Wang 3,  Fei Yan 4,  Qian Li 5
Affiliations

Affiliations

  • 1 Department of Ultrasound, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China; Henan Province Engineering Research Center for Ultrasound-Targeted Nanomaterials and Minimally Invasive Interventional Technology, Zhengzhou, 450008, China.
  • 2 State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • 3 Department of Ultrasound, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100020, China.
  • 4 State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China. Electronic address: [email protected].
  • 5 Department of Ultrasound, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China; Henan Province Engineering Research Center for Ultrasound-Targeted Nanomaterials and Minimally Invasive Interventional Technology, Zhengzhou, 450008, China. Electronic address: [email protected].
PMID: 41671925 DOI: 10.1016/j.bioadv.2026.214770
Abstract

Myocardial ischemia/reperfusion (MIR) injury remains a major clinical challenge with limited therapeutic options. Although molecular hydrogen (H₂) possesses therapeutic potential, its clinical translation is hindered by poor solubility and the lack of targeted delivery and real-time monitoring capabilities. To address this, we developed hydrogen-loaded lipid microbubbles (H₂-MBs) for ultrasound-triggered, spatially controlled H₂ delivery. The fabricated H₂-MBs exhibited uniform spherical morphology (0.92 ± 0.03 μm), high concentration ((1.14 ± 0.07) × 1010 bubbles/mL), and efficient H₂ encapsulation, enabling real-time contrast-enhanced ultrasound imaging. In a rat model of MIR injury, intravenous injection of H₂-MBs followed by ultrasound-targeted microbubble destruction (UTMD) significantly improved cardiac function (ejection fraction and fractional shortening), reduced infarct size, and attenuated tissue damage. Mechanistic studies revealed that ultrasound-targeted H₂ release suppressed H₂O₂-induced PANoptosis-a synergistic cell death pathway-by concurrently downregulating key mediators of Pyroptosis (cleaved Caspase-1, GSDMD), Apoptosis (cleaved Caspase-3/8, Bax/Bcl-2 ratio), and Necroptosis (p-RIPK1, p-RIPK3, p-MLKL). Our work presents a robust theranostic microsystem for image-guided, spatiotemporally controlled gas delivery, offering a promising strategy to combat MIR injury through coordinated modulation of inflammatory programmed cell death.

Keywords

Acoustic delivery; Hydrogen; Microbubbles; Myocardial ischemia/reperfusion injury; PANoptosis; Theranostics.

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