Controlled Release of Hydrogen-Carrying Perfluorocarbons for Ischemia Myocardium-Targeting 19 F MRI-Guided Reperfusion Injury Therapy

Adv Sci (Weinh). 2023 Oct;10(29):e2304178. doi: 10.1002/advs.202304178. Epub 2023 Aug 18.

Abstract

Hydrogen gas is recently proven to have anti-oxidative and anti-inflammation effects on ischemia-reperfusion injury. However, the efficacy of hydrogen therapy is limited by the efficiency of hydrogen storage, targeted delivery, and controlled release. In this study, H2 -PFOB nanoemulsions (NEs) is developed with high hydrogen loading capacity for targeted ischemic myocardium precision therapy. The hydrogen-carrying capacity of H2 -PFOB NEs is determined by gas chromatography and microelectrode methods. Positive uptake of H2 -PFOB NEs in ischemia-reperfusion myocardium and the influence of hydrogen on 19 F-MR signal are quantitatively visualized using a 9.4T MR imaging system. The biological therapeutic effects of H2 -PFOB NEs are examined on a myocardial ischemia-reperfusion injury mouse model. The results illustrated that the developed H2 -PFOB NEs can efficaciously achieve specific infiltration into ischemic myocardium and exhibit excellent antioxidant and anti-inflammatory properties on myocardial ischemia-reperfusion injury, which can be dynamically visualized by 19 F-MR imaging system. Moreover, hydrogen burst release induced by low-intensity focused ultrasound (LIFU) irradiation further promotes the therapeutic effect of H2 -PFOB NEs with a favorable biosafety profile. In this study, the potential therapeutic effects of H2 -PFOB NEs is fully unfolded, which may hold great potential for future hydrogen-based precision therapeutic applications tailored to ischemia-reperfusion injury.

Keywords: NLRP3 inflammasome; hydrogen gas; myocardial ischemia-reperfusion injury; perfluorocarbon; precision medicine.

MeSH terms

  • Animals
  • Delayed-Action Preparations / therapeutic use
  • Fluorocarbons* / pharmacology
  • Fluorocarbons* / therapeutic use
  • Hydrogen / therapeutic use
  • Ischemia
  • Magnetic Resonance Imaging
  • Mice
  • Myocardial Reperfusion Injury* / diagnostic imaging
  • Myocardial Reperfusion Injury* / drug therapy
  • Myocardium
  • Reperfusion

Substances

  • perflubron
  • Hydrogen
  • Delayed-Action Preparations
  • Fluorocarbons