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

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 19F-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 19F-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.